DOI: 10.1242/dev.123.1.217. Mutations affecting neural survival in the zebrafish <i>Danio rerio</i>

Mutations affecting neural survival in the zebrafish Danio rerio

10.1242/dev.123.1.217

Crossref journal-article

The Company of Biologists

Development (237)

Abstract

ABSTRACT Programmed cell death is a prominent feature of normal animal development. During neurogenesis, naturally occurring cell death is a mechanism to eliminate neurons that fail to make appropriate connections. To prevent accidental cell death, mechanisms that trigger programmed cell death, as well as the genetic components of the cell death program, are tightly controlled. In a large-scale mutagenesis screen for embryonic lethal mutations in zebrafish Danio rerio we have found 481 mutations with a neural degeneration phenotype. Here, we present 50 mutations that fall into two classes (termed spacehead and fala-like) that are characterized by two main features: first, they appear to affect cell survival primarily within the neuroectodermal lineages during somitogenesis, and second, they show an altered brain morphology at or before 28 hours of development. Evidence for the specificity of cell death within the central nervous system comes from visual inspection of dying cells and analysis of DNA fragmentation, a process associated with apoptotic cell death. In mutants, the level of dying cells is significantly increased in brain and spinal cord. Furthermore, at the end of somitogenesis, the cell count of radial glia and trigeminal neurons is reduced in some mutants of the spacehead class. A variety of neurodegenerative disorders in mouse and humans have been associated with abnormal levels of programmed cell death within the central nervous system. The mutations presented here might provide a genetic framework to aid in the understanding of the etiology of degenerative and physiological disorders within the CNS and the activation of inappropriate programmed cell death.

Bibliography

Abdelilah, S., Mountcastle-Shah, E., Harvey, M., Solnica-Krezel, L., Schier, A. F., Stemple, D. L., Malicki, J., Neuhauss, S. C. F., Zwartkruis, F., Stainier, D. Y. R., Rangini, Z., & Driever, W. (1996). Mutations affecting neural survival in the zebrafish Danio rerio. Development, 123(1), 217â227.

Authors 12

Salim Abdelilah (first)
Eliza Mountcastle-Shah (additional)
Michele Harvey (additional)
Lilianna Solnica-Krezel (additional)
Alexander F. Schier (additional)
Derek L. Stemple (additional)
Jarema Malicki (additional)
Stephan C. F. Neuhauss (additional)
Fried Zwartkruis (additional)
Didier Y. R. Stainier (additional)
Zehava Rangini (additional)
Wolfgang Driever (additional)

References 68 Referenced 62

10.1242/dev.117.1.29 / Development / Programmed cell death during Drosophila embryogenesis by Abrams (1993)
10.1016/0896-6273(89)90040-8 / Neuron / Trophic factors and neuronal survival by Barde (1989)
10.3171/jns.1974.41.3.0350 / J. Neurosurg / Effect of systemic arterial hypotension on the rate of cerebrospinal fluid formation in dogs by Carey (1974)
10.1038/345410a0 / Nature / The identification and suppression of inherited neurodegeneration in Caenorhabditis elegans by Chalfie (1990)
10.1016/0896-6273(93)90072-Y / Neuron / Apoptosis: final common pathway of photoreceptor death in rd, rds, and rhodopsin mutant mice by Chang (1993)
10.1002/neu.480230915 / J. Neurobiol / Excitotoxic cell death by Choi (1992)
10.1073/pnas.40.10.1014 / Proc. Natl. Acad. Sci. USA / A nerve growth-stimulating factor isolated from sarcomas 37 and 180 by Cohen (1954)
10.1080/09553009214551201 / J. Rad. Biol / Internucleosomal DNA cleavage should not be the sole criterion for identifying apoptosis by Collins (1992)
10.1016/0092-8674(94)90378-6 / Cell / Mice lacking nerve growth factor display perinatal loss of sensory and sympathetic neurons yet develop basal forebrain cholinergic neurons by Crowley (1994)
{'key': '2023072810025419300_DEVELOP_123_1_217C10', 'volume-title': 'Physiology and Pathophysiology of the Cerebrospinal Fluid', 'author': 'Davson', 'year': '1987'} / Physiology and Pathophysiology of the Cerebrospinal Fluid by Davson (1987)
10.1017/S0317167100040865 / Can. J. Neurol. Sci / Acute and chronic cerebral white matter damage in neonatal hydrocephalus by Del Bigio (1994)
10.1242/dev.123.1.37 / Development / A genetic screen for mutations affecting embryogenesis in zebrafish by Driever (1996)
10.1038/320269a0 / Nature / Pathway selection by growth cones of identified motoneurons in live zebrafish embryos by Eisen (1986)
10.1016/0092-8674(86)90004-8 / Cell / Genetic control of programmed cell death in the nematode C. elegans by Ellis (1986)
10.1146/annurev.cb.07.110191.003311 / Ann. Rev. Cell Biol / Mechanisms and functions of cell death by Ellis (1991)
10.1038/368147a0 / Nature / Mice lacking brain-derived neurotrophic factor develop with sensory deficits by Ernfors (1994)
10.1242/dev.120.1.71 / Development / Expression of the zebrafish gene hlx-1 in the prechordal plate and during CNS development by Fjose (1994)
10.1083/jcb.119.3.493 / J. Cell Biol / Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation by Gavrieli (1992)
10.1016/0012-1606(88)90245-X / Dev. Biol / A neural degeneration mutation that spares primary neurons in the zebrafish by Grunwald (1988)
10.1002/jez.1401110308 / J. Exp. Zool / Proliferation, differentiation and degeneration in the spinal ganglia of the chick embryo under normal and experimental conditions by Hamburger (1949)
10.1002/neu.480230904 / J. Neurobiol / History of the discovery of neuronal death in embryos by Hamburger (1992)
10.1016/0092-8674(94)90506-1 / Cell / The C. elegans cell survival gene ced-9 encodes a functional homolog of the mammalian proto-oncogene bcl-2 by Hengartner (1994)
{'key': '2023072810025419300_DEVELOP_123_1_217C23', 'first-page': '929', 'article-title': 'Neuronal survival and synapse formation', 'volume-title': 'In Principles of Neural Science', 'author': 'Jessel', 'year': '1991'} / In Principles of Neural Science / Neuronal survival and synapse formation by Jessel (1991)
10.1016/0092-8674(94)90377-8 / Cell / Targeted disruption of the BDNF gene perturbs brain and sensory neuron development but not motor neuron development by Jones (1994)
10.1016/0165-3806(94)90022-1 / Brain Res. Dev. Brain Res / Apoptotic degeneration in the arhinencephalic brain of the mouse mutant Pdn/Pdn by Keino (1994)
10.1038/bjc.1972.33 / Br. J. Cancer / Apoptosis: a basic biological phenomenon with wide ranging implications in tissue kinetics by Kerr (1972)
{'key': '2023072810025419300_DEVELOP_123_1_217C27', 'first-page': '561', 'article-title': 'Primary neurons of the zebrafish', 'volume-title': 'In Signals and Sense', 'author': 'Kimmel', 'year': '1990'} / In Signals and Sense / Primary neurons of the zebrafish by Kimmel (1990)
10.1002/aja.1002030302 / Dev. Dyn / Stages of embryonic development of the zebrafish by Kimmel (1995)
10.1096/fasebj.8.10.8050673 / FASEB J / Role of neurotrophins in mouse neuronal development by Klein (1994)
10.1016/S0092-8674(05)80088-1 / Cell / Targeted disruption of the trkB neurotrophin receptor gene results in nervous system lesions and neonatal death by Klein (1993)
10.1038/368249a0 / Nature / Disruption of the neurotrophin-3 receptor gene trk C eliminates Ia muscle afferents and results in abnormal movement by Klein (1994)
10.1242/dev.118.2.417 / Development / Zebrafish primary neurons initiate expression of the LIM homeodomain protein Isl-1 at the end of gastrulation by Korzh (1993)
10.1038/353267a0 / Nature / Expression pattern of zebrafish pax genes suggests a role in early brain regionalization by Krauss (1991)
10.1016/0092-8674(92)90286-L / Cell / Targeted mutation of the gene encoding the low affinity NGF receptor p75 leads to deficits in the peripheral sensory nervous system by Lee (1992)
10.1002/j.1460-2075.1987.tb02347.x / EMBO J / The nerve growth factor: thirty-five years later by Levi-Montalcini (1987)
10.1242/dev.123.1.263 / Development / Mutations affecting development of the zebrafish retina by Malicki (1996)
10.1016/S0960-9822(00)00048-8 / Curr. Biol / Large-scale mutagenesis in the zebrafish: in search of genes controlling development in a vertebrate by Mullins (1994)
10.1242/dev.121.4.1183 / Development / The lurcher gene induces apoptotic death in cerebellar Purkinje cells by Norman (1995)
10.1146/annurev.ne.14.030191.002321 / Ann. Rev. Neurosci / Cell death during development of the nervous system by Oppenheim (1991)
10.1093/nar/21.5.1087 / Nucl. Acids Res / Cloning of the zebrafish krox-20 gene (krx-20) and its expression during hindbrain development by Oxtoby (1993)
10.1038/356397a0 / Nature / Social controls on cell survival and cell death by Raff (1992)
10.1126/science.8235590 / Science / Programmed cell death and the control of cell survival: Lessons from the nervous system by Raff (1993)
{'key': '2023072810025419300_DEVELOP_123_1_217C43', 'first-page': '89', 'article-title': 'Ultrastructural study of cell death in Caenorhabditis elegans', 'volume': '67', 'author': 'Robertson', 'year': '1982', 'journal-title': 'J. Embryol. Exp. Morphol'} / J. Embryol. Exp. Morphol / Ultrastructural study of cell death in Caenorhabditis elegans by Robertson (1982)
10.1126/science.154.3749.604 / Science / Death in embryonic systems by Saunders (1966)
10.1242/dev.123.1.165 / Development / Mutations affecting the development of the embryonic zebrafish brain by Schier (1996)
10.1002/bies.950160604 / BioEssays / Ced-3/ICE: Evolutionarily conserved regulation of cell death by Schwartz (1994)
10.1038/368246a0 / Nature / Severe sensory and sympathetic neuropathies in mice carrying a disrupted Trk/NGF receptor gene by Smeyne (1994)
10.1093/genetics/136.4.1401 / Genetics / Efficient recovery of ENU-induced mutations from the zebrafish germline by Solnica-Krezel (1994)
10.1242/dev.123.1.285 / Development / Mutations affecting the formation and function of the cardiovascular system in the zebrafish embryo by Stainier (1996)
10.1126/science.7878463 / Science / Mechanisms and genes of cellular suicide by Steller (1995)
10.1242/dev.123.1.117 / Development / Mutations affecting development of the notochord in zebrafish by Stemple (1996)
10.1038/291293a0 / Nature / Production of clones of homozygous diploid zebrafish (Brachydanio rerio) by Streisinger (1981)
10.1016/0012-1606(77)90158-0 / Dev. Biol / Post-embryonic cell lineages of the nematode, Caenorhabditis elegans by Sulston (1977)
10.1016/0166-2236(91)90097-E / Trends Neurosci / The changing scene of neurotrophic factors by Thoenen (1991)
10.1126/science.7878464 / Science / Apoptosis in the pathogenesis and treatment of disease by Thompson (1995)
10.1016/0896-6273(91)90334-V / Neuron / The homeodomain LIM protein Isl-1 is expressed in subsets of neurons and endocrine cells in the adult rat by Thor (1991)
10.1016/0896-6273(90)90194-K / Neuron / Organization of hindbrain segments in the zebrafish embryo by Trevarrow (1990)
10.1146/annurev.ne.07.030184.001131 / Annu. Rev. Neurosci / Cell death in invertebrate nervous systems by Truman (1984)
10.1016/0092-8674(94)90350-6 / Cell / An evolutionary perspective on apoptosis by Vaux (1994)
10.1016/0092-8674(93)80065-M / Cell / Bcl-2-deficient mice demonstrate fulminant lymphoid apoptosis, polycystic kidneys and hypopigmented hair by Veis (1993)
{'key': '2023072810025419300_DEVELOP_123_1_217C61', 'first-page': '27', 'article-title': 'Modulation of CSF production by alterations in cerebral perfusion pressure', 'volume': '355', 'author': 'Weiss', 'year': '1978', 'journal-title': 'Arch. Neurol'} / Arch. Neurol / Modulation of CSF production by alterations in cerebral perfusion pressure by Weiss (1978)
{'key': '2023072810025419300_DEVELOP_123_1_217C62', 'volume-title': 'The Zebrafish Book', 'author': 'Westerfield', 'year': '1994'} / The Zebrafish Book by Westerfield (1994)
10.1126/science.8171319 / Science / Genetic control of programmed cell death in Drosophila by White (1994)
10.1016/S0074-7696(08)62312-8 / Int. Rev. Cytol / Cell death: the significance of apoptosis by Wyllie (1980)
10.1016/S0959-437X(95)90060-8 / Curr. Gen. Dev / The genetic regulation of apoptosis by Wyllie (1995)
10.1016/0092-8674(93)90248-O / Cell / Control of cell pattern in the neural tube: motor neuron induction by diffusible factors from notochord and floor plate by Yamada (1993)
10.1016/0092-8674(93)90485-9 / Cell / The C. elegans cell death gene ced-3 encodes a protein similar to mammalian interleukin-1β-converting enzyme by Yuan (1993)
10.1096/fasebj.7.5.8462789 / FASEB J / Delayed internucleosomal DNA fragmentation in programmed cell death by Zakeri (1993)

Dates

Type	When
Created	4 years, 4 months ago (April 25, 2021, 10:50 p.m.)
Deposited	2 years ago (July 28, 2023, 6:03 a.m.)
Indexed	1 month, 3 weeks ago (July 2, 2025, 3:11 p.m.)
Issued	28 years, 8 months ago (Dec. 1, 1996)
Published	28 years, 8 months ago (Dec. 1, 1996)
Published Online	28 years, 8 months ago (Dec. 1, 1996)
Published Print	28 years, 8 months ago (Dec. 1, 1996)

Funders 0

None

BibTeX

@article{Abdelilah_1996, title={Mutations affecting neural survival in the zebrafish Danio rerio}, volume={123}, ISSN={1477-9129}, url={http://dx.doi.org/10.1242/dev.123.1.217}, DOI={10.1242/dev.123.1.217}, number={1}, journal={Development}, publisher={The Company of Biologists}, author={Abdelilah, Salim and Mountcastle-Shah, Eliza and Harvey, Michele and Solnica-Krezel, Lilianna and Schier, Alexander F. and Stemple, Derek L. and Malicki, Jarema and Neuhauss, Stephan C. F. and Zwartkruis, Fried and Stainier, Didier Y. R. and Rangini, Zehava and Driever, Wolfgang}, year={1996}, month=dec, pages={217–227} }

JSON

{
  "indexed": {
    "date-parts": [
      [
        2025,
        7,
        2
      ]
    ],
    "date-time": "2025-07-02T19:11:16Z",
    "timestamp": 1751483476445
  },
  "reference-count": 68,
  "publisher": "The Company of Biologists",
  "issue": "1",
  "license": [
    {
      "start": {
        "date-parts": [
          [
            1996,
            12,
            1
          ]
        ],
        "date-time": "1996-12-01T00:00:00Z",
        "timestamp": 849398400000
      },
      "content-version": "vor",
      "delay-in-days": 0,
      "URL": "http://www.biologists.com/user-licence-1-1/"
    }
  ],
  "content-domain": {
    "domain": [],
    "crossmark-restriction": false
  },
  "published-print": {
    "date-parts": [
      [
        1996,
        12,
        1
      ]
    ]
  },
  "abstract": "<jats:title>ABSTRACT</jats:title>\n               <jats:p>Programmed cell death is a prominent feature of normal animal development. During neurogenesis, naturally occurring cell death is a mechanism to eliminate neurons that fail to make appropriate connections. To prevent accidental cell death, mechanisms that trigger programmed cell death, as well as the genetic components of the cell death program, are tightly controlled.</jats:p>\n               <jats:p>In a large-scale mutagenesis screen for embryonic lethal mutations in zebrafish Danio rerio we have found 481 mutations with a neural degeneration phenotype. Here, we present 50 mutations that fall into two classes (termed spacehead and fala-like) that are characterized by two main features: first, they appear to affect cell survival primarily within the neuroectodermal lineages during somitogenesis, and second, they show an altered brain morphology at or before 28 hours of development. Evidence for the specificity of cell death within the central nervous system comes from visual inspection of dying cells and analysis of DNA fragmentation, a process associated with apoptotic cell death. In mutants, the level of dying cells is significantly increased in brain and spinal cord. Furthermore, at the end of somitogenesis, the cell count of radial glia and trigeminal neurons is reduced in some mutants of the spacehead class.</jats:p>\n               <jats:p>A variety of neurodegenerative disorders in mouse and humans have been associated with abnormal levels of programmed cell death within the central nervous system. The mutations presented here might provide a genetic framework to aid in the understanding of the etiology of degenerative and physiological disorders within the CNS and the activation of inappropriate programmed cell death.</jats:p>",
  "DOI": "10.1242/dev.123.1.217",
  "type": "journal-article",
  "created": {
    "date-parts": [
      [
        2021,
        4,
        26
      ]
    ],
    "date-time": "2021-04-26T02:50:33Z",
    "timestamp": 1619405433000
  },
  "page": "217-227",
  "source": "Crossref",
  "is-referenced-by-count": 62,
  "title": "Mutations affecting neural survival in the zebrafish <i>Danio rerio</i>",
  "prefix": "10.1242",
  "volume": "123",
  "author": [
    {
      "given": "Salim",
      "family": "Abdelilah",
      "sequence": "first",
      "affiliation": [
        {
          "name": "Massachusetts General Hospital and Harvard Medical School, Building 149, 13th Street, Charlestown, MA 02129, USA"
        }
      ]
    },
    {
      "given": "Eliza",
      "family": "Mountcastle-Shah",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Massachusetts General Hospital and Harvard Medical School, Building 149, 13th Street, Charlestown, MA 02129, USA"
        }
      ]
    },
    {
      "given": "Michele",
      "family": "Harvey",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Massachusetts General Hospital and Harvard Medical School, Building 149, 13th Street, Charlestown, MA 02129, USA"
        }
      ]
    },
    {
      "given": "Lilianna",
      "family": "Solnica-Krezel",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Massachusetts General Hospital and Harvard Medical School, Building 149, 13th Street, Charlestown, MA 02129, USA"
        }
      ]
    },
    {
      "given": "Alexander F.",
      "family": "Schier",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Massachusetts General Hospital and Harvard Medical School, Building 149, 13th Street, Charlestown, MA 02129, USA"
        }
      ]
    },
    {
      "given": "Derek L.",
      "family": "Stemple",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Massachusetts General Hospital and Harvard Medical School, Building 149, 13th Street, Charlestown, MA 02129, USA"
        }
      ]
    },
    {
      "given": "Jarema",
      "family": "Malicki",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Massachusetts General Hospital and Harvard Medical School, Building 149, 13th Street, Charlestown, MA 02129, USA"
        }
      ]
    },
    {
      "given": "Stephan C. F.",
      "family": "Neuhauss",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Massachusetts General Hospital and Harvard Medical School, Building 149, 13th Street, Charlestown, MA 02129, USA"
        }
      ]
    },
    {
      "given": "Fried",
      "family": "Zwartkruis",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Massachusetts General Hospital and Harvard Medical School, Building 149, 13th Street, Charlestown, MA 02129, USA"
        }
      ]
    },
    {
      "given": "Didier Y. R.",
      "family": "Stainier",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Massachusetts General Hospital and Harvard Medical School, Building 149, 13th Street, Charlestown, MA 02129, USA"
        }
      ]
    },
    {
      "given": "Zehava",
      "family": "Rangini",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Massachusetts General Hospital and Harvard Medical School, Building 149, 13th Street, Charlestown, MA 02129, USA"
        }
      ]
    },
    {
      "given": "Wolfgang",
      "family": "Driever",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Massachusetts General Hospital and Harvard Medical School, Building 149, 13th Street, Charlestown, MA 02129, USA"
        }
      ]
    }
  ],
  "member": "237",
  "published-online": {
    "date-parts": [
      [
        1996,
        12,
        1
      ]
    ]
  },
  "reference": [
    {
      "key": "2023072810025419300_DEVELOP_123_1_217C1",
      "doi-asserted-by": "publisher",
      "first-page": "29",
      "DOI": "10.1242/dev.117.1.29",
      "article-title": "Programmed cell death during Drosophila embryogenesis",
      "volume": "117",
      "author": "Abrams",
      "year": "1993",
      "journal-title": "Development"
    },
    {
      "key": "2023072810025419300_DEVELOP_123_1_217C2",
      "doi-asserted-by": "publisher",
      "first-page": "1525",
      "DOI": "10.1016/0896-6273(89)90040-8",
      "article-title": "Trophic factors and neuronal survival",
      "volume": "2",
      "author": "Barde",
      "year": "1989",
      "journal-title": "Neuron"
    },
    {
      "key": "2023072810025419300_DEVELOP_123_1_217C3",
      "doi-asserted-by": "publisher",
      "first-page": "350",
      "DOI": "10.3171/jns.1974.41.3.0350",
      "article-title": "Effect of systemic arterial hypotension on the rate of cerebrospinal fluid formation in dogs",
      "volume": "41",
      "author": "Carey",
      "year": "1974",
      "journal-title": "J. Neurosurg"
    },
    {
      "key": "2023072810025419300_DEVELOP_123_1_217C4",
      "doi-asserted-by": "publisher",
      "first-page": "410",
      "DOI": "10.1038/345410a0",
      "article-title": "The identification and suppression of inherited neurodegeneration in Caenorhabditis elegans",
      "volume": "345",
      "author": "Chalfie",
      "year": "1990",
      "journal-title": "Nature"
    },
    {
      "key": "2023072810025419300_DEVELOP_123_1_217C5",
      "doi-asserted-by": "publisher",
      "first-page": "595",
      "DOI": "10.1016/0896-6273(93)90072-Y",
      "article-title": "Apoptosis: final common pathway of photoreceptor death in rd, rds, and rhodopsin mutant mice",
      "volume": "11",
      "author": "Chang",
      "year": "1993",
      "journal-title": "Neuron"
    },
    {
      "key": "2023072810025419300_DEVELOP_123_1_217C6",
      "doi-asserted-by": "publisher",
      "first-page": "1261",
      "DOI": "10.1002/neu.480230915",
      "article-title": "Excitotoxic cell death",
      "volume": "23",
      "author": "Choi",
      "year": "1992",
      "journal-title": "J. Neurobiol"
    },
    {
      "key": "2023072810025419300_DEVELOP_123_1_217C7",
      "doi-asserted-by": "publisher",
      "first-page": "1014",
      "DOI": "10.1073/pnas.40.10.1014",
      "article-title": "A nerve growth-stimulating factor isolated from sarcomas 37 and 180",
      "volume": "40",
      "author": "Cohen",
      "year": "1954",
      "journal-title": "Proc. Natl. Acad. Sci. USA"
    },
    {
      "key": "2023072810025419300_DEVELOP_123_1_217C8",
      "doi-asserted-by": "publisher",
      "first-page": "451",
      "DOI": "10.1080/09553009214551201",
      "article-title": "Internucleosomal DNA cleavage should not be the sole criterion for identifying apoptosis",
      "volume": "61",
      "author": "Collins",
      "year": "1992",
      "journal-title": "J. Rad. Biol"
    },
    {
      "key": "2023072810025419300_DEVELOP_123_1_217C9",
      "doi-asserted-by": "publisher",
      "first-page": "1001",
      "DOI": "10.1016/0092-8674(94)90378-6",
      "article-title": "Mice lacking nerve growth factor display perinatal loss of sensory and sympathetic neurons yet develop basal forebrain cholinergic neurons",
      "volume": "76",
      "author": "Crowley",
      "year": "1994",
      "journal-title": "Cell"
    },
    {
      "key": "2023072810025419300_DEVELOP_123_1_217C10",
      "volume-title": "Physiology and Pathophysiology of the Cerebrospinal Fluid",
      "author": "Davson",
      "year": "1987"
    },
    {
      "key": "2023072810025419300_DEVELOP_123_1_217C11",
      "doi-asserted-by": "publisher",
      "first-page": "299",
      "DOI": "10.1017/S0317167100040865",
      "article-title": "Acute and chronic cerebral white matter damage in neonatal hydrocephalus",
      "volume": "21",
      "author": "Del Bigio",
      "year": "1994",
      "journal-title": "Can. J. Neurol. Sci"
    },
    {
      "key": "2023072810025419300_DEVELOP_123_1_217C12",
      "doi-asserted-by": "publisher",
      "first-page": "37",
      "DOI": "10.1242/dev.123.1.37",
      "article-title": "A genetic screen for mutations affecting embryogenesis in zebrafish",
      "volume": "123",
      "author": "Driever",
      "year": "1996",
      "journal-title": "Development"
    },
    {
      "key": "2023072810025419300_DEVELOP_123_1_217C13",
      "doi-asserted-by": "publisher",
      "first-page": "269",
      "DOI": "10.1038/320269a0",
      "article-title": "Pathway selection by growth cones of identified motoneurons in live zebrafish embryos",
      "volume": "320",
      "author": "Eisen",
      "year": "1986",
      "journal-title": "Nature"
    },
    {
      "key": "2023072810025419300_DEVELOP_123_1_217C14",
      "doi-asserted-by": "publisher",
      "first-page": "817",
      "DOI": "10.1016/0092-8674(86)90004-8",
      "article-title": "Genetic control of programmed cell death in the nematode C. elegans",
      "volume": "44",
      "author": "Ellis",
      "year": "1986",
      "journal-title": "Cell"
    },
    {
      "key": "2023072810025419300_DEVELOP_123_1_217C15",
      "doi-asserted-by": "publisher",
      "first-page": "663",
      "DOI": "10.1146/annurev.cb.07.110191.003311",
      "article-title": "Mechanisms and functions of cell death",
      "volume": "7",
      "author": "Ellis",
      "year": "1991",
      "journal-title": "Ann. Rev. Cell Biol"
    },
    {
      "key": "2023072810025419300_DEVELOP_123_1_217C16",
      "doi-asserted-by": "publisher",
      "first-page": "147",
      "DOI": "10.1038/368147a0",
      "article-title": "Mice lacking brain-derived neurotrophic factor develop with sensory deficits",
      "volume": "368",
      "author": "Ernfors",
      "year": "1994",
      "journal-title": "Nature"
    },
    {
      "key": "2023072810025419300_DEVELOP_123_1_217C17",
      "doi-asserted-by": "publisher",
      "first-page": "71",
      "DOI": "10.1242/dev.120.1.71",
      "article-title": "Expression of the zebrafish gene hlx-1 in the prechordal plate and during CNS development",
      "volume": "120",
      "author": "Fjose",
      "year": "1994",
      "journal-title": "Development"
    },
    {
      "key": "2023072810025419300_DEVELOP_123_1_217C18",
      "doi-asserted-by": "publisher",
      "first-page": "493",
      "DOI": "10.1083/jcb.119.3.493",
      "article-title": "Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation",
      "volume": "119",
      "author": "Gavrieli",
      "year": "1992",
      "journal-title": "J. Cell Biol"
    },
    {
      "key": "2023072810025419300_DEVELOP_123_1_217C19",
      "doi-asserted-by": "publisher",
      "first-page": "115",
      "DOI": "10.1016/0012-1606(88)90245-X",
      "article-title": "A neural degeneration mutation that spares primary neurons in the zebrafish",
      "volume": "126",
      "author": "Grunwald",
      "year": "1988",
      "journal-title": "Dev. Biol"
    },
    {
      "key": "2023072810025419300_DEVELOP_123_1_217C20",
      "doi-asserted-by": "publisher",
      "first-page": "457",
      "DOI": "10.1002/jez.1401110308",
      "article-title": "Proliferation, differentiation and degeneration in the spinal ganglia of the chick embryo under normal and experimental conditions",
      "volume": "111",
      "author": "Hamburger",
      "year": "1949",
      "journal-title": "J. Exp. Zool"
    },
    {
      "key": "2023072810025419300_DEVELOP_123_1_217C21",
      "doi-asserted-by": "publisher",
      "first-page": "1116",
      "DOI": "10.1002/neu.480230904",
      "article-title": "History of the discovery of neuronal death in embryos",
      "volume": "23",
      "author": "Hamburger",
      "year": "1992",
      "journal-title": "J. Neurobiol"
    },
    {
      "key": "2023072810025419300_DEVELOP_123_1_217C22",
      "doi-asserted-by": "publisher",
      "first-page": "665",
      "DOI": "10.1016/0092-8674(94)90506-1",
      "article-title": "The C. elegans cell survival gene ced-9 encodes a functional homolog of the mammalian proto-oncogene bcl-2",
      "volume": "76",
      "author": "Hengartner",
      "year": "1994",
      "journal-title": "Cell"
    },
    {
      "key": "2023072810025419300_DEVELOP_123_1_217C23",
      "first-page": "929",
      "article-title": "Neuronal survival and synapse formation",
      "volume-title": "In Principles of Neural Science",
      "author": "Jessel",
      "year": "1991"
    },
    {
      "key": "2023072810025419300_DEVELOP_123_1_217C24",
      "doi-asserted-by": "publisher",
      "first-page": "989",
      "DOI": "10.1016/0092-8674(94)90377-8",
      "article-title": "Targeted disruption of the BDNF gene perturbs brain and sensory neuron development but not motor neuron development",
      "volume": "76",
      "author": "Jones",
      "year": "1994",
      "journal-title": "Cell"
    },
    {
      "key": "2023072810025419300_DEVELOP_123_1_217C25",
      "doi-asserted-by": "publisher",
      "first-page": "161",
      "DOI": "10.1016/0165-3806(94)90022-1",
      "article-title": "Apoptotic degeneration in the arhinencephalic brain of the mouse mutant Pdn/Pdn",
      "volume": "78",
      "author": "Keino",
      "year": "1994",
      "journal-title": "Brain Res. Dev. Brain Res"
    },
    {
      "key": "2023072810025419300_DEVELOP_123_1_217C26",
      "doi-asserted-by": "publisher",
      "first-page": "239",
      "DOI": "10.1038/bjc.1972.33",
      "article-title": "Apoptosis: a basic biological phenomenon with wide ranging implications in tissue kinetics",
      "volume": "26",
      "author": "Kerr",
      "year": "1972",
      "journal-title": "Br. J. Cancer"
    },
    {
      "key": "2023072810025419300_DEVELOP_123_1_217C27",
      "first-page": "561",
      "article-title": "Primary neurons of the zebrafish",
      "volume-title": "In Signals and Sense",
      "author": "Kimmel",
      "year": "1990"
    },
    {
      "key": "2023072810025419300_DEVELOP_123_1_217C28",
      "doi-asserted-by": "publisher",
      "first-page": "253",
      "DOI": "10.1002/aja.1002030302",
      "article-title": "Stages of embryonic development of the zebrafish",
      "volume": "203",
      "author": "Kimmel",
      "year": "1995",
      "journal-title": "Dev. Dyn"
    },
    {
      "key": "2023072810025419300_DEVELOP_123_1_217C29",
      "doi-asserted-by": "publisher",
      "first-page": "738",
      "DOI": "10.1096/fasebj.8.10.8050673",
      "article-title": "Role of neurotrophins in mouse neuronal development",
      "volume": "8",
      "author": "Klein",
      "year": "1994",
      "journal-title": "FASEB J"
    },
    {
      "key": "2023072810025419300_DEVELOP_123_1_217C30",
      "doi-asserted-by": "publisher",
      "first-page": "113",
      "DOI": "10.1016/S0092-8674(05)80088-1",
      "article-title": "Targeted disruption of the trkB neurotrophin receptor gene results in nervous system lesions and neonatal death",
      "volume": "75",
      "author": "Klein",
      "year": "1993",
      "journal-title": "Cell"
    },
    {
      "key": "2023072810025419300_DEVELOP_123_1_217C31",
      "doi-asserted-by": "publisher",
      "first-page": "249",
      "DOI": "10.1038/368249a0",
      "article-title": "Disruption of the neurotrophin-3 receptor gene trk C eliminates Ia muscle afferents and results in abnormal movement",
      "volume": "368",
      "author": "Klein",
      "year": "1994",
      "journal-title": "Nature"
    },
    {
      "key": "2023072810025419300_DEVELOP_123_1_217C32",
      "doi-asserted-by": "publisher",
      "first-page": "417",
      "DOI": "10.1242/dev.118.2.417",
      "article-title": "Zebrafish primary neurons initiate expression of the LIM homeodomain protein Isl-1 at the end of gastrulation",
      "volume": "118",
      "author": "Korzh",
      "year": "1993",
      "journal-title": "Development"
    },
    {
      "key": "2023072810025419300_DEVELOP_123_1_217C33",
      "doi-asserted-by": "publisher",
      "first-page": "267",
      "DOI": "10.1038/353267a0",
      "article-title": "Expression pattern of zebrafish pax genes suggests a role in early brain regionalization",
      "volume": "353",
      "author": "Krauss",
      "year": "1991",
      "journal-title": "Nature"
    },
    {
      "key": "2023072810025419300_DEVELOP_123_1_217C34",
      "doi-asserted-by": "publisher",
      "first-page": "737",
      "DOI": "10.1016/0092-8674(92)90286-L",
      "article-title": "Targeted mutation of the gene encoding the low affinity NGF receptor p75 leads to deficits in the peripheral sensory nervous system",
      "volume": "69",
      "author": "Lee",
      "year": "1992",
      "journal-title": "Cell"
    },
    {
      "key": "2023072810025419300_DEVELOP_123_1_217C35",
      "doi-asserted-by": "publisher",
      "first-page": "1145",
      "DOI": "10.1002/j.1460-2075.1987.tb02347.x",
      "article-title": "The nerve growth factor: thirty-five years later",
      "volume": "6",
      "author": "Levi-Montalcini",
      "year": "1987",
      "journal-title": "EMBO J"
    },
    {
      "key": "2023072810025419300_DEVELOP_123_1_217C36",
      "doi-asserted-by": "publisher",
      "first-page": "263",
      "DOI": "10.1242/dev.123.1.263",
      "article-title": "Mutations affecting development of the zebrafish retina",
      "volume": "123",
      "author": "Malicki",
      "year": "1996",
      "journal-title": "Development"
    },
    {
      "key": "2023072810025419300_DEVELOP_123_1_217C37",
      "doi-asserted-by": "publisher",
      "first-page": "189",
      "DOI": "10.1016/S0960-9822(00)00048-8",
      "article-title": "Large-scale mutagenesis in the zebrafish: in search of genes controlling development in a vertebrate",
      "volume": "4",
      "author": "Mullins",
      "year": "1994",
      "journal-title": "Curr. Biol"
    },
    {
      "key": "2023072810025419300_DEVELOP_123_1_217C38",
      "doi-asserted-by": "publisher",
      "first-page": "1183",
      "DOI": "10.1242/dev.121.4.1183",
      "article-title": "The lurcher gene induces apoptotic death in cerebellar Purkinje cells",
      "volume": "121",
      "author": "Norman",
      "year": "1995",
      "journal-title": "Development"
    },
    {
      "key": "2023072810025419300_DEVELOP_123_1_217C39",
      "doi-asserted-by": "publisher",
      "first-page": "453",
      "DOI": "10.1146/annurev.ne.14.030191.002321",
      "article-title": "Cell death during development of the nervous system",
      "volume": "14",
      "author": "Oppenheim",
      "year": "1991",
      "journal-title": "Ann. Rev. Neurosci"
    },
    {
      "key": "2023072810025419300_DEVELOP_123_1_217C40",
      "doi-asserted-by": "publisher",
      "first-page": "1087",
      "DOI": "10.1093/nar/21.5.1087",
      "article-title": "Cloning of the zebrafish krox-20 gene (krx-20) and its expression during hindbrain development",
      "volume": "21",
      "author": "Oxtoby",
      "year": "1993",
      "journal-title": "Nucl. Acids Res"
    },
    {
      "key": "2023072810025419300_DEVELOP_123_1_217C41",
      "doi-asserted-by": "publisher",
      "first-page": "397",
      "DOI": "10.1038/356397a0",
      "article-title": "Social controls on cell survival and cell death",
      "volume": "356",
      "author": "Raff",
      "year": "1992",
      "journal-title": "Nature"
    },
    {
      "key": "2023072810025419300_DEVELOP_123_1_217C42",
      "doi-asserted-by": "publisher",
      "first-page": "695",
      "DOI": "10.1126/science.8235590",
      "article-title": "Programmed cell death and the control of cell survival: Lessons from the nervous system",
      "volume": "262",
      "author": "Raff",
      "year": "1993",
      "journal-title": "Science"
    },
    {
      "key": "2023072810025419300_DEVELOP_123_1_217C43",
      "first-page": "89",
      "article-title": "Ultrastructural study of cell death in Caenorhabditis elegans",
      "volume": "67",
      "author": "Robertson",
      "year": "1982",
      "journal-title": "J. Embryol. Exp. Morphol"
    },
    {
      "key": "2023072810025419300_DEVELOP_123_1_217C44",
      "doi-asserted-by": "publisher",
      "first-page": "604",
      "DOI": "10.1126/science.154.3749.604",
      "article-title": "Death in embryonic systems",
      "volume": "154",
      "author": "Saunders",
      "year": "1966",
      "journal-title": "Science"
    },
    {
      "key": "2023072810025419300_DEVELOP_123_1_217C45",
      "doi-asserted-by": "publisher",
      "first-page": "165",
      "DOI": "10.1242/dev.123.1.165",
      "article-title": "Mutations affecting the development of the embryonic zebrafish brain",
      "volume": "123",
      "author": "Schier",
      "year": "1996",
      "journal-title": "Development"
    },
    {
      "key": "2023072810025419300_DEVELOP_123_1_217C46",
      "doi-asserted-by": "publisher",
      "first-page": "387",
      "DOI": "10.1002/bies.950160604",
      "article-title": "Ced-3/ICE: Evolutionarily conserved regulation of cell death",
      "volume": "16",
      "author": "Schwartz",
      "year": "1994",
      "journal-title": "BioEssays"
    },
    {
      "key": "2023072810025419300_DEVELOP_123_1_217C47",
      "doi-asserted-by": "publisher",
      "first-page": "246",
      "DOI": "10.1038/368246a0",
      "article-title": "Severe sensory and sympathetic neuropathies in mice carrying a disrupted Trk/NGF receptor gene",
      "volume": "368",
      "author": "Smeyne",
      "year": "1994",
      "journal-title": "Nature"
    },
    {
      "key": "2023072810025419300_DEVELOP_123_1_217C48",
      "doi-asserted-by": "publisher",
      "first-page": "1401",
      "DOI": "10.1093/genetics/136.4.1401",
      "article-title": "Efficient recovery of ENU-induced mutations from the zebrafish germline",
      "volume": "136",
      "author": "Solnica-Krezel",
      "year": "1994",
      "journal-title": "Genetics"
    },
    {
      "key": "2023072810025419300_DEVELOP_123_1_217C49",
      "doi-asserted-by": "publisher",
      "first-page": "285",
      "DOI": "10.1242/dev.123.1.285",
      "article-title": "Mutations affecting the formation and function of the cardiovascular system in the zebrafish embryo",
      "volume": "123",
      "author": "Stainier",
      "year": "1996",
      "journal-title": "Development"
    },
    {
      "key": "2023072810025419300_DEVELOP_123_1_217C50",
      "doi-asserted-by": "publisher",
      "first-page": "1445",
      "DOI": "10.1126/science.7878463",
      "article-title": "Mechanisms and genes of cellular suicide",
      "volume": "267",
      "author": "Steller",
      "year": "1995",
      "journal-title": "Science"
    },
    {
      "key": "2023072810025419300_DEVELOP_123_1_217C51",
      "doi-asserted-by": "publisher",
      "first-page": "117",
      "DOI": "10.1242/dev.123.1.117",
      "article-title": "Mutations affecting development of the notochord in zebrafish",
      "volume": "123",
      "author": "Stemple",
      "year": "1996",
      "journal-title": "Development"
    },
    {
      "key": "2023072810025419300_DEVELOP_123_1_217C52",
      "doi-asserted-by": "publisher",
      "first-page": "293",
      "DOI": "10.1038/291293a0",
      "article-title": "Production of clones of homozygous diploid zebrafish (Brachydanio rerio)",
      "volume": "291",
      "author": "Streisinger",
      "year": "1981",
      "journal-title": "Nature"
    },
    {
      "key": "2023072810025419300_DEVELOP_123_1_217C53",
      "doi-asserted-by": "publisher",
      "first-page": "110",
      "DOI": "10.1016/0012-1606(77)90158-0",
      "article-title": "Post-embryonic cell lineages of the nematode, Caenorhabditis elegans",
      "volume": "56",
      "author": "Sulston",
      "year": "1977",
      "journal-title": "Dev. Biol"
    },
    {
      "key": "2023072810025419300_DEVELOP_123_1_217C54",
      "doi-asserted-by": "publisher",
      "first-page": "165",
      "DOI": "10.1016/0166-2236(91)90097-E",
      "article-title": "The changing scene of neurotrophic factors",
      "volume": "14",
      "author": "Thoenen",
      "year": "1991",
      "journal-title": "Trends Neurosci"
    },
    {
      "key": "2023072810025419300_DEVELOP_123_1_217C55",
      "doi-asserted-by": "publisher",
      "first-page": "1456",
      "DOI": "10.1126/science.7878464",
      "article-title": "Apoptosis in the pathogenesis and treatment of disease",
      "volume": "267",
      "author": "Thompson",
      "year": "1995",
      "journal-title": "Science"
    },
    {
      "key": "2023072810025419300_DEVELOP_123_1_217C56",
      "doi-asserted-by": "publisher",
      "first-page": "881",
      "DOI": "10.1016/0896-6273(91)90334-V",
      "article-title": "The homeodomain LIM protein Isl-1 is expressed in subsets of neurons and endocrine cells in the adult rat",
      "volume": "7",
      "author": "Thor",
      "year": "1991",
      "journal-title": "Neuron"
    },
    {
      "key": "2023072810025419300_DEVELOP_123_1_217C57",
      "doi-asserted-by": "publisher",
      "first-page": "669",
      "DOI": "10.1016/0896-6273(90)90194-K",
      "article-title": "Organization of hindbrain segments in the zebrafish embryo",
      "volume": "4",
      "author": "Trevarrow",
      "year": "1990",
      "journal-title": "Neuron"
    },
    {
      "key": "2023072810025419300_DEVELOP_123_1_217C58",
      "doi-asserted-by": "publisher",
      "first-page": "171",
      "DOI": "10.1146/annurev.ne.07.030184.001131",
      "article-title": "Cell death in invertebrate nervous systems",
      "volume": "7",
      "author": "Truman",
      "year": "1984",
      "journal-title": "Annu. Rev. Neurosci"
    },
    {
      "key": "2023072810025419300_DEVELOP_123_1_217C59",
      "doi-asserted-by": "publisher",
      "first-page": "777",
      "DOI": "10.1016/0092-8674(94)90350-6",
      "article-title": "An evolutionary perspective on apoptosis",
      "volume": "76",
      "author": "Vaux",
      "year": "1994",
      "journal-title": "Cell"
    },
    {
      "key": "2023072810025419300_DEVELOP_123_1_217C60",
      "doi-asserted-by": "publisher",
      "first-page": "229",
      "DOI": "10.1016/0092-8674(93)80065-M",
      "article-title": "Bcl-2-deficient mice demonstrate fulminant lymphoid apoptosis, polycystic kidneys and hypopigmented hair",
      "volume": "75",
      "author": "Veis",
      "year": "1993",
      "journal-title": "Cell"
    },
    {
      "key": "2023072810025419300_DEVELOP_123_1_217C61",
      "first-page": "27",
      "article-title": "Modulation of CSF production by alterations in cerebral perfusion pressure",
      "volume": "355",
      "author": "Weiss",
      "year": "1978",
      "journal-title": "Arch. Neurol"
    },
    {
      "key": "2023072810025419300_DEVELOP_123_1_217C62",
      "volume-title": "The Zebrafish Book",
      "author": "Westerfield",
      "year": "1994"
    },
    {
      "key": "2023072810025419300_DEVELOP_123_1_217C63",
      "doi-asserted-by": "publisher",
      "first-page": "677",
      "DOI": "10.1126/science.8171319",
      "article-title": "Genetic control of programmed cell death in Drosophila",
      "volume": "264",
      "author": "White",
      "year": "1994",
      "journal-title": "Science"
    },
    {
      "key": "2023072810025419300_DEVELOP_123_1_217C64",
      "doi-asserted-by": "publisher",
      "first-page": "251",
      "DOI": "10.1016/S0074-7696(08)62312-8",
      "article-title": "Cell death: the significance of apoptosis",
      "volume": "68",
      "author": "Wyllie",
      "year": "1980",
      "journal-title": "Int. Rev. Cytol"
    },
    {
      "key": "2023072810025419300_DEVELOP_123_1_217C65",
      "doi-asserted-by": "publisher",
      "first-page": "97",
      "DOI": "10.1016/S0959-437X(95)90060-8",
      "article-title": "The genetic regulation of apoptosis",
      "volume": "5",
      "author": "Wyllie",
      "year": "1995",
      "journal-title": "Curr. Gen. Dev"
    },
    {
      "key": "2023072810025419300_DEVELOP_123_1_217C66",
      "doi-asserted-by": "publisher",
      "first-page": "673",
      "DOI": "10.1016/0092-8674(93)90248-O",
      "article-title": "Control of cell pattern in the neural tube: motor neuron induction by diffusible factors from notochord and floor plate",
      "volume": "73",
      "author": "Yamada",
      "year": "1993",
      "journal-title": "Cell"
    },
    {
      "key": "2023072810025419300_DEVELOP_123_1_217C67",
      "doi-asserted-by": "publisher",
      "first-page": "641",
      "DOI": "10.1016/0092-8674(93)90485-9",
      "article-title": "The C. elegans cell death gene ced-3 encodes a protein similar to mammalian interleukin-1\u03b2-converting enzyme",
      "volume": "75",
      "author": "Yuan",
      "year": "1993",
      "journal-title": "Cell"
    },
    {
      "key": "2023072810025419300_DEVELOP_123_1_217C68",
      "doi-asserted-by": "publisher",
      "first-page": "470",
      "DOI": "10.1096/fasebj.7.5.8462789",
      "article-title": "Delayed internucleosomal DNA fragmentation in programmed cell death",
      "volume": "7",
      "author": "Zakeri",
      "year": "1993",
      "journal-title": "FASEB J"
    }
  ],
  "container-title": "Development",
  "original-title": [],
  "language": "en",
  "link": [
    {
      "URL": "https://journals.biologists.com/dev/article-pdf/123/1/217/3084268/develop_123_1_217.pdf",
      "content-type": "application/pdf",
      "content-version": "vor",
      "intended-application": "syndication"
    },
    {
      "URL": "https://journals.biologists.com/dev/article-pdf/123/1/217/3084268/develop_123_1_217.pdf",
      "content-type": "unspecified",
      "content-version": "vor",
      "intended-application": "similarity-checking"
    }
  ],
  "deposited": {
    "date-parts": [
      [
        2023,
        7,
        28
      ]
    ],
    "date-time": "2023-07-28T10:03:47Z",
    "timestamp": 1690538627000
  },
  "score": 1,
  "resource": {
    "primary": {
      "URL": "https://journals.biologists.com/dev/article/123/1/217/39322/Mutations-affecting-neural-survival-in-the"
    }
  },
  "subtitle": [],
  "short-title": [],
  "issued": {
    "date-parts": [
      [
        1996,
        12,
        1
      ]
    ]
  },
  "references-count": 68,
  "journal-issue": {
    "issue": "1",
    "published-print": {
      "date-parts": [
        [
          1996,
          12,
          1
        ]
      ]
    }
  },
  "URL": "http://dx.doi.org/10.1242/dev.123.1.217",
  "relation": {},
  "ISSN": [
    "0950-1991",
    "1477-9129"
  ],
  "subject": [],
  "published": {
    "date-parts": [
      [
        1996,
        12,
        1
      ]
    ]
  }
}