DOI: 10.1534/genetics.107.082487. A Drosophila Gain-of-Function Screen for Candidate Genes Involved in Steroid-Dependent Neuroendocrine Cell Remodeling

A Drosophila Gain-of-Function Screen for Candidate Genes Involved in Steroid-Dependent Neuroendocrine Cell Remodeling

10.1534/genetics.107.082487

Crossref journal-article

Oxford University Press (OUP)

Genetics (286)

Abstract

Abstract The normal functioning of neuroendocrine systems requires that many neuropeptidergic cells change, to alter transmitter identity and concentration, electrical properties, and cellular morphology in response to hormonal cues. During insect metamorphosis, a pulse of circulating steroids, ecdysteroids, governs the dramatic remodeling of larval neurons to serve adult-specific functions. To identify molecular mechanisms underlying metamorphic remodeling, we conducted a neuropeptidergic cell-targeted, gain-of-function genetic screen. We screened 6097 lines. Each line permitted Gal4-regulated transcription of flanking genes. A total of 58 lines, representing 51 loci, showed defects in neuropeptide-mediated developmental transitions (ecdysis or wing expansion) when crossed to the panneuropeptidergic Gal4 driver, 386Y-Gal4. In a secondary screen, we found 29 loci that produced wing expansion defects when crossed to a crustacean cardioactive peptide (CCAP)/bursicon neuron-specific Gal4 driver. At least 14 loci disrupted the formation or maintenance of adult-specific CCAP/bursicon cell projections during metamorphosis. These include components of the insulin and epidermal growth factor signaling pathways, an ecdysteroid-response gene, cabut, and an ubiquitin-specific protease gene, fat facets, with known functions in neuronal development. Several additional genes, including three micro-RNA loci and two factors related to signaling by Myb-like proto-oncogenes, have not previously been implicated in steroid signaling or neuronal remodeling.

Bibliography

Zhao, T., Gu, T., Rice, H. C., McAdams, K. L., Roark, K. M., Lawson, K., Gauthier, S. A., Reagan, K. L., & Hewes, R. S. (2008). A Drosophila Gain-of-Function Screen for Candidate Genes Involved in Steroid-Dependent Neuroendocrine Cell Remodeling. Genetics, 178(2), 883â901.

Authors 9

Tao Zhao (first)
Tingting Gu (additional)
Heather C Rice (additional)
Kathleen L McAdams (additional)
Kimberly M Roark (additional)
Kaylan Lawson (additional)
Sebastien A Gauthier (additional)
Kathleen L Reagan (additional)
Randall S Hewes (additional)

References 112 Referenced 37

10.1093/genetics/155.2.733 / Genetics (2000)
10.1016/S0092-8674(03)00204-6 / Cell (2003)
10.1016/j.conb.2007.03.013 / Curr. Opin. Neurobiol. (2007)
10.1016/S1534-5807(03)00228-4 / Dev. Cell (2003)
{'key': '2022110405475187800_BIB5', 'first-page': '57', 'volume': '66', 'year': '1981', 'journal-title': 'J. Embryol. Exp. Morphol.'} / J. Embryol. Exp. Morphol. (1981)
10.1242/jeb.205.17.2555 / J. Exp. Biol. (2002)
10.1128/MCB.20.24.9317-9330.2000 / Mol. Cell. Biol. (2000)
10.1186/1471-2202-5-48 / BMC Neurosci. (2004)
10.1038/nature01228 / Nature (2002)
10.1186/gb-2005-6-12-r99 / Genome Biol. (2005)
10.1534/genetics.104.026427 / Genetics (2004)
10.1038/ng1794 / Nat. Genet. (2006)
10.1074/jbc.M702634200 / J. Biol. Chem. (2007)
10.1016/S0092-8674(03)00231-9 / Cell (2003)
10.1242/dev.02191 / Development (2006)
10.1038/sj.cdd.4401861 / Cell Death Differ. (2006)
10.1016/S0959-4388(00)00211-7 / Curr. Opin. Neurobiol. (2001)
10.1152/physrev.2001.81.3.1197 / Physiol. Rev. (2001)
{'key': '2022110405475187800_BIB19', 'first-page': '103', 'volume': '5', 'year': '1985', 'journal-title': 'Dev. Genet.'} / Dev. Genet. (1985)
10.1016/S0960-9822(00)00625-4 / Curr. Biol. (2000)
10.1242/dev.00205 / Development (2003)
10.1242/dev.02376 / Development (2006)
10.1242/dev.122.3.937 / Development (1996)
10.1523/JNEUROSCI.4938-03.2004 / J. Neurosci. (2004)
{'key': '2022110405475187800_BIB25', 'year': '1994'} (1994)
10.1016/j.cub.2004.06.051 / Curr. Biol. (2004)
10.1038/35086595 / Nature (2001)
10.1016/S0960-9822(98)70441-5 / Curr. Biol. (1998)
10.1080/10409230600914344 / Crit. Rev. Biochem. Mol. Biol. (2006)
10.1002/(SICI)1097-4695(199903)38:4<455::AID-NEU2>3.0.CO;2-F / J. Neurobiol. (1999)
10.1186/gb-2003-5-1-r1 / Genome Biol. (2003)
{'key': '2022110405475187800_BIB32', 'year': '2002'} (2002)
10.1242/jeb.200.5.869 / J. Exp. Biol. (1997)
10.1016/0022-1910(65)90137-X / J. Insect Physiol. (1965)
10.1083/jcb.200303026 / J. Cell Biol. (2003)
10.1093/nar/gkj068 / Nucleic Acids Res. (2006)
10.1371/journal.pcbi.0010013 / PLoS Comput. Biol. (2005)
{'key': '2022110405475187800_BIB38', 'first-page': '256', 'volume': '50', 'year': '1943', 'journal-title': 'Rev. Suisse Zool.'} / Rev. Suisse Zool. (1943)
10.1016/j.pneurobio.2004.05.005 / Prog. Neurobiol. (2004)
{'key': '2022110405475187800_BIB40', 'first-page': '697', 'volume': '168', 'year': '1991', 'journal-title': 'J. Comp. Physiol. A'} / J. Comp. Physiol. A (1991)
10.1093/genetics/155.4.1711 / Genetics (2000)
10.1242/dev.00404 / Development (2003)
10.1523/JNEUROSCI.1759-06.2006 / J. Neurosci. (2006)
10.1002/neu.20126 / J. Neurobiol. (2005)
10.1016/j.neuron.2006.05.013 / Neuron (2006)
10.1016/j.neuron.2006.11.001 / Neuron (2006)
10.1093/nar/gkg129 / Nucleic Acids Res. (2003)
10.1016/j.cub.2006.06.027 / Curr. Biol. (2006)
10.1002/cne.10563 / J. Comp. Neurol. (2003)
10.1016/j.devcel.2006.09.009 / Dev. Cell (2006)
10.1016/0092-8674(91)90572-G / Cell (1991)
10.1016/S0960-9822(01)00124-5 / Curr. Biol. (2001)
10.1242/dev.127.7.1517 / Development (2000)
10.1016/j.cell.2005.04.016 / Cell (2005)
10.1016/S0896-6273(00)80701-1 / Neuron (1999)
10.1016/S0896-6273(00)00155-0 / Neuron (2000)
10.1038/299250a0 / Nature (1982)
10.1101/gad.1255204 / Genes Dev. (2004)
10.1016/j.cell.2005.10.040 / Cell (2005)
10.1016/S0896-6273(01)00495-0 / Neuron (2001)
10.1523/JNEUROSCI.1821-04.2004 / J. Neurosci. (2004)
10.1523/JNEUROSCI.3916-05.2006 / J. Neurosci. (2006)
10.1073/pnas.0409916102 / Proc. Natl. Acad. Sci. USA (2005)
10.1038/sj.emboj.7601484 / EMBO J. (2007)
10.1038/nature04691 / Nature (2006)
10.1016/S0925-4773(03)00159-X / Mech. Dev. (2003)
10.1126/science.1089035 / Science (2003)
{'key': '2022110405475187800_BIB68', 'year': '2004'} (2004)
10.1016/S0896-6273(00)80963-0 / Neuron (1997)
10.1534/genetics.105.044453 / Genetics (2005)
10.1016/j.ydbio.2005.08.048 / Dev. Biol. (2005)
10.1016/j.pneurobio.2007.06.005 / Prog. Neurobiol. (2007)
{'key': '2022110405475187800_BIB73', 'year': '1994'} (1994)
10.1242/jeb.201.2.193 / J. Exp. Biol. (1998)
10.1242/dev.00503 / Development (2003)
10.1093/genetics/160.3.1035 / Genetics (2002)
10.1016/j.ydbio.2003.12.003 / Dev. Biol. (2004)
10.1242/jeb.78.1.77 / J. Exp. Biol. (1979)
10.1002/neu.480250707 / J. Neurobiol. (1994)
10.1242/dev.119.4.1251 / Development (1993)
10.1196/annals.1376.022 / Ann. NY Acad. Sci. (2006)
10.1073/pnas.93.22.12418 / Proc. Natl. Acad. Sci. USA (1996)
10.1242/dev.125.6.1049 / Development (1998)
10.4161/cc.6.7.4064 / Cell Cycle (2007)
10.1007/s00441-006-0211-7 / Cell Tissue Res. (2006)
10.1242/dev.125.11.2053 / Development (1998)
10.1016/S0012-1606(03)00208-2 / Dev. Biol. (2003)
10.1371/journal.pbio.0020429 / PLoS Biol. (2004)
10.1523/JNEUROSCI.0455-06.2006 / J. Neurosci. (2006)
{'key': '2022110405475187800_BIB90', 'year': '2003'} (2003)
10.1242/jeb.98.1.385 / J. Exp. Biol. (1982)
10.1523/JNEUROSCI.21-17-06673.2001 / J. Neurosci. (2001)
10.1016/0092-8674(93)90359-X / Cell (1993)
10.1016/j.devcel.2005.07.004 / Dev. Cell (2005)
10.1101/gad.374406 / Genes Dev. (2006)
10.1038/ng1314 / Nat. Genet. (2004)
10.1016/S0739-7240(02)00148-0 / Domest. Anim. Endocrinol. (2002)
10.1038/362471a0 / Nature (1993)
10.1186/gb-2007-8-7-r145 / Genome Biol. (2007)
10.2144/000112476 / Biotechniques (2007)
{'key': '2022110405475187800_BIB101', 'first-page': '805', 'volume': '57', 'year': '1973', 'journal-title': 'J. Exp. Biol.'} / J. Exp. Biol. (1973)
10.1002/neu.480231005 / J. Neurobiol. (1992)
10.1159/000111398 / Dev. Neurosci. (1996)
10.1242/dev.120.1.219 / Development (1994)
10.1093/genetics/162.1.229 / Genetics (2002)
10.1046/j.1365-2826.2002.00798.x / J. Neuroendocrinol. (2002)
10.1016/S0896-6273(03)00295-2 / Neuron (2003)
10.1016/S0301-0082(03)00102-3 / Prog. Neurobiol. (2003)
10.1242/dev.01928 / Development (2005)
10.1016/0092-8674(92)90266-F / Cell (1992)
10.1038/366476a0 / Nature (1993)
10.1242/jeb.204.20.3483 / J. Exp. Biol. (2001)

Dates

Type	When
Created	17 years, 6 months ago (Feb. 1, 2008, 9:07 p.m.)
Deposited	2 years, 9 months ago (Nov. 4, 2022, 1:56 a.m.)
Indexed	1 month, 1 week ago (July 19, 2025, 11:30 p.m.)
Issued	17 years, 7 months ago (Feb. 1, 2008)
Published	17 years, 7 months ago (Feb. 1, 2008)
Published Online	17 years, 7 months ago (Feb. 1, 2008)
Published Print	17 years, 7 months ago (Feb. 1, 2008)

Funders 0

None

BibTeX

@article{Zhao_2008, title={A Drosophila Gain-of-Function Screen for Candidate Genes Involved in Steroid-Dependent Neuroendocrine Cell Remodeling}, volume={178}, ISSN={1943-2631}, url={http://dx.doi.org/10.1534/genetics.107.082487}, DOI={10.1534/genetics.107.082487}, number={2}, journal={Genetics}, publisher={Oxford University Press (OUP)}, author={Zhao, Tao and Gu, Tingting and Rice, Heather C and McAdams, Kathleen L and Roark, Kimberly M and Lawson, Kaylan and Gauthier, Sebastien A and Reagan, Kathleen L and Hewes, Randall S}, year={2008}, month=feb, pages={883–901} }

JSON

{
  "indexed": {
    "date-parts": [
      [
        2025,
        7,
        20
      ]
    ],
    "date-time": "2025-07-20T03:30:03Z",
    "timestamp": 1752982203960
  },
  "reference-count": 112,
  "publisher": "Oxford University Press (OUP)",
  "issue": "2",
  "license": [
    {
      "start": {
        "date-parts": [
          [
            2008,
            2,
            1
          ]
        ],
        "date-time": "2008-02-01T00:00:00Z",
        "timestamp": 1201824000000
      },
      "content-version": "vor",
      "delay-in-days": 0,
      "URL": "https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model"
    }
  ],
  "content-domain": {
    "domain": [],
    "crossmark-restriction": false
  },
  "published-print": {
    "date-parts": [
      [
        2008,
        2,
        1
      ]
    ]
  },
  "abstract": "<jats:title>Abstract</jats:title>\n               <jats:p>The normal functioning of neuroendocrine systems requires that many neuropeptidergic cells change, to alter transmitter identity and concentration, electrical properties, and cellular morphology in response to hormonal cues. During insect metamorphosis, a pulse of circulating steroids, ecdysteroids, governs the dramatic remodeling of larval neurons to serve adult-specific functions. To identify molecular mechanisms underlying metamorphic remodeling, we conducted a neuropeptidergic cell-targeted, gain-of-function genetic screen. We screened 6097 lines. Each line permitted Gal4-regulated transcription of flanking genes. A total of 58 lines, representing 51 loci, showed defects in neuropeptide-mediated developmental transitions (ecdysis or wing expansion) when crossed to the panneuropeptidergic Gal4 driver, 386Y-Gal4. In a secondary screen, we found 29 loci that produced wing expansion defects when crossed to a crustacean cardioactive peptide (CCAP)/bursicon neuron-specific Gal4 driver. At least 14 loci disrupted the formation or maintenance of adult-specific CCAP/bursicon cell projections during metamorphosis. These include components of the insulin and epidermal growth factor signaling pathways, an ecdysteroid-response gene, cabut, and an ubiquitin-specific protease gene, fat facets, with known functions in neuronal development. Several additional genes, including three micro-RNA loci and two factors related to signaling by Myb-like proto-oncogenes, have not previously been implicated in steroid signaling or neuronal remodeling.</jats:p>",
  "DOI": "10.1534/genetics.107.082487",
  "type": "journal-article",
  "created": {
    "date-parts": [
      [
        2008,
        2,
        2
      ]
    ],
    "date-time": "2008-02-02T02:07:40Z",
    "timestamp": 1201918060000
  },
  "page": "883-901",
  "source": "Crossref",
  "is-referenced-by-count": 37,
  "title": "A Drosophila Gain-of-Function Screen for Candidate Genes Involved in Steroid-Dependent Neuroendocrine Cell Remodeling",
  "prefix": "10.1093",
  "volume": "178",
  "author": [
    {
      "given": "Tao",
      "family": "Zhao",
      "sequence": "first",
      "affiliation": [
        {
          "name": "Department of Zoology , University of Oklahoma, Norman, Oklahoma 73019 and"
        }
      ]
    },
    {
      "given": "Tingting",
      "family": "Gu",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Department of Zoology , University of Oklahoma, Norman, Oklahoma 73019 and"
        }
      ]
    },
    {
      "given": "Heather C",
      "family": "Rice",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Department of Zoology , University of Oklahoma, Norman, Oklahoma 73019 and"
        }
      ]
    },
    {
      "given": "Kathleen L",
      "family": "McAdams",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Department of Zoology , University of Oklahoma, Norman, Oklahoma 73019 and"
        }
      ]
    },
    {
      "given": "Kimberly M",
      "family": "Roark",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Department of Zoology , University of Oklahoma, Norman, Oklahoma 73019 and"
        }
      ]
    },
    {
      "given": "Kaylan",
      "family": "Lawson",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Department of Zoology , University of Oklahoma, Norman, Oklahoma 73019 and"
        }
      ]
    },
    {
      "given": "Sebastien A",
      "family": "Gauthier",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Department of Zoology , University of Oklahoma, Norman, Oklahoma 73019 and"
        }
      ]
    },
    {
      "given": "Kathleen L",
      "family": "Reagan",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Department of Zoology , University of Oklahoma, Norman, Oklahoma 73019 and"
        }
      ]
    },
    {
      "given": "Randall S",
      "family": "Hewes",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Department of Zoology , University of Oklahoma, Norman, Oklahoma 73019 and"
        },
        {
          "name": "Department of Cell Biology , University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104"
        }
      ]
    }
  ],
  "member": "286",
  "published-online": {
    "date-parts": [
      [
        2008,
        2,
        1
      ]
    ]
  },
  "reference": [
    {
      "key": "2022110405475187800_BIB1",
      "doi-asserted-by": "crossref",
      "first-page": "733",
      "DOI": "10.1093/genetics/155.2.733",
      "volume": "155",
      "year": "2000",
      "journal-title": "Genetics"
    },
    {
      "key": "2022110405475187800_BIB2",
      "doi-asserted-by": "crossref",
      "first-page": "73",
      "DOI": "10.1016/S0092-8674(03)00204-6",
      "volume": "113",
      "year": "2003",
      "journal-title": "Cell"
    },
    {
      "key": "2022110405475187800_BIB3",
      "doi-asserted-by": "crossref",
      "first-page": "325",
      "DOI": "10.1016/j.conb.2007.03.013",
      "volume": "17",
      "year": "2007",
      "journal-title": "Curr. Opin. Neurobiol."
    },
    {
      "key": "2022110405475187800_BIB4",
      "doi-asserted-by": "crossref",
      "first-page": "337",
      "DOI": "10.1016/S1534-5807(03)00228-4",
      "volume": "5",
      "year": "2003",
      "journal-title": "Dev. Cell"
    },
    {
      "key": "2022110405475187800_BIB5",
      "first-page": "57",
      "volume": "66",
      "year": "1981",
      "journal-title": "J. Embryol. Exp. Morphol."
    },
    {
      "key": "2022110405475187800_BIB6",
      "doi-asserted-by": "crossref",
      "first-page": "2555",
      "DOI": "10.1242/jeb.205.17.2555",
      "volume": "205",
      "year": "2002",
      "journal-title": "J. Exp. Biol."
    },
    {
      "key": "2022110405475187800_BIB7",
      "doi-asserted-by": "crossref",
      "first-page": "9317",
      "DOI": "10.1128/MCB.20.24.9317-9330.2000",
      "volume": "20",
      "year": "2000",
      "journal-title": "Mol. Cell. Biol."
    },
    {
      "key": "2022110405475187800_BIB8",
      "doi-asserted-by": "crossref",
      "first-page": "48",
      "DOI": "10.1186/1471-2202-5-48",
      "volume": "5",
      "year": "2004",
      "journal-title": "BMC Neurosci."
    },
    {
      "key": "2022110405475187800_BIB9",
      "doi-asserted-by": "crossref",
      "first-page": "833",
      "DOI": "10.1038/nature01228",
      "volume": "420",
      "year": "2002",
      "journal-title": "Nature"
    },
    {
      "key": "2022110405475187800_BIB10",
      "doi-asserted-by": "crossref",
      "first-page": "R99",
      "DOI": "10.1186/gb-2005-6-12-r99",
      "volume": "6",
      "year": "2005",
      "journal-title": "Genome Biol."
    },
    {
      "key": "2022110405475187800_BIB11",
      "doi-asserted-by": "crossref",
      "first-page": "761",
      "DOI": "10.1534/genetics.104.026427",
      "volume": "167",
      "year": "2004",
      "journal-title": "Genetics"
    },
    {
      "key": "2022110405475187800_BIB12",
      "doi-asserted-by": "crossref",
      "first-page": "S2",
      "DOI": "10.1038/ng1794",
      "volume": "38",
      "year": "2006",
      "journal-title": "Nat. Genet."
    },
    {
      "key": "2022110405475187800_BIB13",
      "doi-asserted-by": "crossref",
      "first-page": "29368",
      "DOI": "10.1074/jbc.M702634200",
      "volume": "282",
      "year": "2007",
      "journal-title": "J. Biol. Chem."
    },
    {
      "key": "2022110405475187800_BIB14",
      "doi-asserted-by": "crossref",
      "first-page": "25",
      "DOI": "10.1016/S0092-8674(03)00231-9",
      "volume": "113",
      "year": "2003",
      "journal-title": "Cell"
    },
    {
      "key": "2022110405475187800_BIB15",
      "doi-asserted-by": "crossref",
      "first-page": "275",
      "DOI": "10.1242/dev.02191",
      "volume": "133",
      "year": "2006",
      "journal-title": "Development"
    },
    {
      "key": "2022110405475187800_BIB16",
      "doi-asserted-by": "crossref",
      "first-page": "1752",
      "DOI": "10.1038/sj.cdd.4401861",
      "volume": "13",
      "year": "2006",
      "journal-title": "Cell Death Differ."
    },
    {
      "key": "2022110405475187800_BIB17",
      "doi-asserted-by": "crossref",
      "first-page": "297",
      "DOI": "10.1016/S0959-4388(00)00211-7",
      "volume": "11",
      "year": "2001",
      "journal-title": "Curr. Opin. Neurobiol."
    },
    {
      "key": "2022110405475187800_BIB18",
      "doi-asserted-by": "crossref",
      "first-page": "1197",
      "DOI": "10.1152/physrev.2001.81.3.1197",
      "volume": "81",
      "year": "2001",
      "journal-title": "Physiol. Rev."
    },
    {
      "key": "2022110405475187800_BIB19",
      "first-page": "103",
      "volume": "5",
      "year": "1985",
      "journal-title": "Dev. Genet."
    },
    {
      "key": "2022110405475187800_BIB20",
      "doi-asserted-by": "crossref",
      "first-page": "943",
      "DOI": "10.1016/S0960-9822(00)00625-4",
      "volume": "10",
      "year": "2000",
      "journal-title": "Curr. Biol."
    },
    {
      "key": "2022110405475187800_BIB21",
      "doi-asserted-by": "crossref",
      "first-page": "271",
      "DOI": "10.1242/dev.00205",
      "volume": "130",
      "year": "2003",
      "journal-title": "Development"
    },
    {
      "key": "2022110405475187800_BIB22",
      "doi-asserted-by": "crossref",
      "first-page": "2223",
      "DOI": "10.1242/dev.02376",
      "volume": "133",
      "year": "2006",
      "journal-title": "Development"
    },
    {
      "key": "2022110405475187800_BIB23",
      "doi-asserted-by": "crossref",
      "first-page": "937",
      "DOI": "10.1242/dev.122.3.937",
      "volume": "122",
      "year": "1996",
      "journal-title": "Development"
    },
    {
      "key": "2022110405475187800_BIB24",
      "doi-asserted-by": "crossref",
      "first-page": "4283",
      "DOI": "10.1523/JNEUROSCI.4938-03.2004",
      "volume": "24",
      "year": "2004",
      "journal-title": "J. Neurosci."
    },
    {
      "key": "2022110405475187800_BIB25",
      "year": "1994"
    },
    {
      "key": "2022110405475187800_BIB26",
      "doi-asserted-by": "crossref",
      "first-page": "1208",
      "DOI": "10.1016/j.cub.2004.06.051",
      "volume": "14",
      "year": "2004",
      "journal-title": "Curr. Biol."
    },
    {
      "key": "2022110405475187800_BIB27",
      "doi-asserted-by": "crossref",
      "first-page": "449",
      "DOI": "10.1038/35086595",
      "volume": "412",
      "year": "2001",
      "journal-title": "Nature"
    },
    {
      "key": "2022110405475187800_BIB28",
      "doi-asserted-by": "crossref",
      "first-page": "1039",
      "DOI": "10.1016/S0960-9822(98)70441-5",
      "volume": "8",
      "year": "1998",
      "journal-title": "Curr. Biol."
    },
    {
      "key": "2022110405475187800_BIB29",
      "doi-asserted-by": "crossref",
      "first-page": "339",
      "DOI": "10.1080/10409230600914344",
      "volume": "41",
      "year": "2006",
      "journal-title": "Crit. Rev. Biochem. Mol. Biol."
    },
    {
      "key": "2022110405475187800_BIB30",
      "doi-asserted-by": "crossref",
      "first-page": "455",
      "DOI": "10.1002/(SICI)1097-4695(199903)38:4<455::AID-NEU2>3.0.CO;2-F",
      "volume": "38",
      "year": "1999",
      "journal-title": "J. Neurobiol."
    },
    {
      "key": "2022110405475187800_BIB31",
      "doi-asserted-by": "crossref",
      "first-page": "R1",
      "DOI": "10.1186/gb-2003-5-1-r1",
      "volume": "5",
      "year": "2003",
      "journal-title": "Genome Biol."
    },
    {
      "key": "2022110405475187800_BIB32",
      "year": "2002"
    },
    {
      "key": "2022110405475187800_BIB33",
      "doi-asserted-by": "crossref",
      "first-page": "869",
      "DOI": "10.1242/jeb.200.5.869",
      "volume": "200",
      "year": "1997",
      "journal-title": "J. Exp. Biol."
    },
    {
      "key": "2022110405475187800_BIB34",
      "doi-asserted-by": "crossref",
      "first-page": "513",
      "DOI": "10.1016/0022-1910(65)90137-X",
      "volume": "11",
      "year": "1965",
      "journal-title": "J. Insect Physiol."
    },
    {
      "key": "2022110405475187800_BIB35",
      "doi-asserted-by": "crossref",
      "first-page": "613",
      "DOI": "10.1083/jcb.200303026",
      "volume": "162",
      "year": "2003",
      "journal-title": "J. Cell Biol."
    },
    {
      "key": "2022110405475187800_BIB36",
      "doi-asserted-by": "crossref",
      "first-page": "D484",
      "DOI": "10.1093/nar/gkj068",
      "volume": "34",
      "year": "2006",
      "journal-title": "Nucleic Acids Res."
    },
    {
      "key": "2022110405475187800_BIB37",
      "doi-asserted-by": "crossref",
      "first-page": "e13",
      "DOI": "10.1371/journal.pcbi.0010013",
      "volume": "1",
      "year": "2005",
      "journal-title": "PLoS Comput. Biol."
    },
    {
      "key": "2022110405475187800_BIB38",
      "first-page": "256",
      "volume": "50",
      "year": "1943",
      "journal-title": "Rev. Suisse Zool."
    },
    {
      "key": "2022110405475187800_BIB39",
      "doi-asserted-by": "crossref",
      "first-page": "311",
      "DOI": "10.1016/j.pneurobio.2004.05.005",
      "volume": "73",
      "year": "2004",
      "journal-title": "Prog. Neurobiol."
    },
    {
      "key": "2022110405475187800_BIB40",
      "first-page": "697",
      "volume": "168",
      "year": "1991",
      "journal-title": "J. Comp. Physiol. A"
    },
    {
      "key": "2022110405475187800_BIB41",
      "doi-asserted-by": "crossref",
      "first-page": "1711",
      "DOI": "10.1093/genetics/155.4.1711",
      "volume": "155",
      "year": "2000",
      "journal-title": "Genetics"
    },
    {
      "key": "2022110405475187800_BIB42",
      "doi-asserted-by": "crossref",
      "first-page": "1771",
      "DOI": "10.1242/dev.00404",
      "volume": "130",
      "year": "2003",
      "journal-title": "Development"
    },
    {
      "key": "2022110405475187800_BIB43",
      "doi-asserted-by": "crossref",
      "first-page": "7860",
      "DOI": "10.1523/JNEUROSCI.1759-06.2006",
      "volume": "26",
      "year": "2006",
      "journal-title": "J. Neurosci."
    },
    {
      "key": "2022110405475187800_BIB44",
      "doi-asserted-by": "crossref",
      "first-page": "235",
      "DOI": "10.1002/neu.20126",
      "volume": "63",
      "year": "2005",
      "journal-title": "J. Neurobiol."
    },
    {
      "key": "2022110405475187800_BIB45",
      "doi-asserted-by": "crossref",
      "first-page": "883",
      "DOI": "10.1016/j.neuron.2006.05.013",
      "volume": "50",
      "year": "2006",
      "journal-title": "Neuron"
    },
    {
      "key": "2022110405475187800_BIB46",
      "doi-asserted-by": "crossref",
      "first-page": "577",
      "DOI": "10.1016/j.neuron.2006.11.001",
      "volume": "52",
      "year": "2006",
      "journal-title": "Neuron"
    },
    {
      "key": "2022110405475187800_BIB47",
      "doi-asserted-by": "crossref",
      "first-page": "51",
      "DOI": "10.1093/nar/gkg129",
      "volume": "31",
      "year": "2003",
      "journal-title": "Nucleic Acids Res."
    },
    {
      "key": "2022110405475187800_BIB48",
      "doi-asserted-by": "crossref",
      "first-page": "1395",
      "DOI": "10.1016/j.cub.2006.06.027",
      "volume": "16",
      "year": "2006",
      "journal-title": "Curr. Biol."
    },
    {
      "key": "2022110405475187800_BIB49",
      "doi-asserted-by": "crossref",
      "first-page": "384",
      "DOI": "10.1002/cne.10563",
      "volume": "457",
      "year": "2003",
      "journal-title": "J. Comp. Neurol."
    },
    {
      "key": "2022110405475187800_BIB50",
      "doi-asserted-by": "crossref",
      "first-page": "441",
      "DOI": "10.1016/j.devcel.2006.09.009",
      "volume": "11",
      "year": "2006",
      "journal-title": "Dev. Cell"
    },
    {
      "key": "2022110405475187800_BIB51",
      "doi-asserted-by": "crossref",
      "first-page": "59",
      "DOI": "10.1016/0092-8674(91)90572-G",
      "volume": "67",
      "year": "1991",
      "journal-title": "Cell"
    },
    {
      "key": "2022110405475187800_BIB52",
      "doi-asserted-by": "crossref",
      "first-page": "417",
      "DOI": "10.1016/S0960-9822(01)00124-5",
      "volume": "11",
      "year": "2001",
      "journal-title": "Curr. Biol."
    },
    {
      "key": "2022110405475187800_BIB53",
      "doi-asserted-by": "crossref",
      "first-page": "1517",
      "DOI": "10.1242/dev.127.7.1517",
      "volume": "127",
      "year": "2000",
      "journal-title": "Development"
    },
    {
      "key": "2022110405475187800_BIB54",
      "doi-asserted-by": "crossref",
      "first-page": "1097",
      "DOI": "10.1016/j.cell.2005.04.016",
      "volume": "121",
      "year": "2005",
      "journal-title": "Cell"
    },
    {
      "key": "2022110405475187800_BIB55",
      "doi-asserted-by": "crossref",
      "first-page": "451",
      "DOI": "10.1016/S0896-6273(00)80701-1",
      "volume": "22",
      "year": "1999",
      "journal-title": "Neuron"
    },
    {
      "key": "2022110405475187800_BIB56",
      "doi-asserted-by": "crossref",
      "first-page": "807",
      "DOI": "10.1016/S0896-6273(00)00155-0",
      "volume": "28",
      "year": "2000",
      "journal-title": "Neuron"
    },
    {
      "key": "2022110405475187800_BIB57",
      "doi-asserted-by": "crossref",
      "first-page": "250",
      "DOI": "10.1038/299250a0",
      "volume": "299",
      "year": "1982",
      "journal-title": "Nature"
    },
    {
      "key": "2022110405475187800_BIB58",
      "doi-asserted-by": "crossref",
      "first-page": "2929",
      "DOI": "10.1101/gad.1255204",
      "volume": "18",
      "year": "2004",
      "journal-title": "Genes Dev."
    },
    {
      "key": "2022110405475187800_BIB59",
      "doi-asserted-by": "crossref",
      "first-page": "1267",
      "DOI": "10.1016/j.cell.2005.10.040",
      "volume": "123",
      "year": "2005",
      "journal-title": "Cell"
    },
    {
      "key": "2022110405475187800_BIB60",
      "doi-asserted-by": "crossref",
      "first-page": "425",
      "DOI": "10.1016/S0896-6273(01)00495-0",
      "volume": "32",
      "year": "2001",
      "journal-title": "Neuron"
    },
    {
      "key": "2022110405475187800_BIB61",
      "doi-asserted-by": "crossref",
      "first-page": "8720",
      "DOI": "10.1523/JNEUROSCI.1821-04.2004",
      "volume": "24",
      "year": "2004",
      "journal-title": "J. Neurosci."
    },
    {
      "key": "2022110405475187800_BIB62",
      "doi-asserted-by": "crossref",
      "first-page": "573",
      "DOI": "10.1523/JNEUROSCI.3916-05.2006",
      "volume": "26",
      "year": "2006",
      "journal-title": "J. Neurosci."
    },
    {
      "key": "2022110405475187800_BIB63",
      "doi-asserted-by": "crossref",
      "first-page": "2820",
      "DOI": "10.1073/pnas.0409916102",
      "volume": "102",
      "year": "2005",
      "journal-title": "Proc. Natl. Acad. Sci. USA"
    },
    {
      "key": "2022110405475187800_BIB64",
      "doi-asserted-by": "crossref",
      "first-page": "380",
      "DOI": "10.1038/sj.emboj.7601484",
      "volume": "26",
      "year": "2007",
      "journal-title": "EMBO J."
    },
    {
      "key": "2022110405475187800_BIB65",
      "doi-asserted-by": "crossref",
      "first-page": "750",
      "DOI": "10.1038/nature04691",
      "volume": "441",
      "year": "2006",
      "journal-title": "Nature"
    },
    {
      "key": "2022110405475187800_BIB66",
      "doi-asserted-by": "crossref",
      "first-page": "1193",
      "DOI": "10.1016/S0925-4773(03)00159-X",
      "volume": "120",
      "year": "2003",
      "journal-title": "Mech. Dev."
    },
    {
      "key": "2022110405475187800_BIB67",
      "doi-asserted-by": "crossref",
      "first-page": "1765",
      "DOI": "10.1126/science.1089035",
      "volume": "302",
      "year": "2003",
      "journal-title": "Science"
    },
    {
      "key": "2022110405475187800_BIB68",
      "year": "2004"
    },
    {
      "key": "2022110405475187800_BIB69",
      "doi-asserted-by": "crossref",
      "first-page": "813",
      "DOI": "10.1016/S0896-6273(00)80963-0",
      "volume": "19",
      "year": "1997",
      "journal-title": "Neuron"
    },
    {
      "key": "2022110405475187800_BIB70",
      "doi-asserted-by": "crossref",
      "first-page": "1137",
      "DOI": "10.1534/genetics.105.044453",
      "volume": "171",
      "year": "2005",
      "journal-title": "Genetics"
    },
    {
      "key": "2022110405475187800_BIB71",
      "doi-asserted-by": "crossref",
      "first-page": "168",
      "DOI": "10.1016/j.ydbio.2005.08.048",
      "volume": "287",
      "year": "2005",
      "journal-title": "Dev. Biol."
    },
    {
      "key": "2022110405475187800_BIB72",
      "doi-asserted-by": "crossref",
      "first-page": "163",
      "DOI": "10.1016/j.pneurobio.2007.06.005",
      "volume": "82",
      "year": "2007",
      "journal-title": "Prog. Neurobiol."
    },
    {
      "key": "2022110405475187800_BIB73",
      "year": "1994"
    },
    {
      "key": "2022110405475187800_BIB74",
      "doi-asserted-by": "crossref",
      "first-page": "193",
      "DOI": "10.1242/jeb.201.2.193",
      "volume": "201",
      "year": "1998",
      "journal-title": "J. Exp. Biol."
    },
    {
      "key": "2022110405475187800_BIB75",
      "doi-asserted-by": "crossref",
      "first-page": "2645",
      "DOI": "10.1242/dev.00503",
      "volume": "130",
      "year": "2003",
      "journal-title": "Development"
    },
    {
      "key": "2022110405475187800_BIB76",
      "doi-asserted-by": "crossref",
      "first-page": "1035",
      "DOI": "10.1093/genetics/160.3.1035",
      "volume": "160",
      "year": "2002",
      "journal-title": "Genetics"
    },
    {
      "key": "2022110405475187800_BIB77",
      "doi-asserted-by": "crossref",
      "first-page": "529",
      "DOI": "10.1016/j.ydbio.2003.12.003",
      "volume": "267",
      "year": "2004",
      "journal-title": "Dev. Biol."
    },
    {
      "key": "2022110405475187800_BIB78",
      "doi-asserted-by": "crossref",
      "first-page": "77",
      "DOI": "10.1242/jeb.78.1.77",
      "volume": "78",
      "year": "1979",
      "journal-title": "J. Exp. Biol."
    },
    {
      "key": "2022110405475187800_BIB79",
      "doi-asserted-by": "crossref",
      "first-page": "819",
      "DOI": "10.1002/neu.480250707",
      "volume": "25",
      "year": "1994",
      "journal-title": "J. Neurobiol."
    },
    {
      "key": "2022110405475187800_BIB80",
      "doi-asserted-by": "crossref",
      "first-page": "1251",
      "DOI": "10.1242/dev.119.4.1251",
      "volume": "119",
      "year": "1993",
      "journal-title": "Development"
    },
    {
      "key": "2022110405475187800_BIB81",
      "doi-asserted-by": "crossref",
      "first-page": "202",
      "DOI": "10.1196/annals.1376.022",
      "volume": "1094",
      "year": "2006",
      "journal-title": "Ann. NY Acad. Sci."
    },
    {
      "key": "2022110405475187800_BIB82",
      "doi-asserted-by": "crossref",
      "first-page": "12418",
      "DOI": "10.1073/pnas.93.22.12418",
      "volume": "93",
      "year": "1996",
      "journal-title": "Proc. Natl. Acad. Sci. USA"
    },
    {
      "key": "2022110405475187800_BIB83",
      "doi-asserted-by": "crossref",
      "first-page": "1049",
      "DOI": "10.1242/dev.125.6.1049",
      "volume": "125",
      "year": "1998",
      "journal-title": "Development"
    },
    {
      "key": "2022110405475187800_BIB84",
      "doi-asserted-by": "crossref",
      "first-page": "830",
      "DOI": "10.4161/cc.6.7.4064",
      "volume": "6",
      "year": "2007",
      "journal-title": "Cell Cycle"
    },
    {
      "key": "2022110405475187800_BIB85",
      "doi-asserted-by": "crossref",
      "first-page": "187",
      "DOI": "10.1007/s00441-006-0211-7",
      "volume": "326",
      "year": "2006",
      "journal-title": "Cell Tissue Res."
    },
    {
      "key": "2022110405475187800_BIB86",
      "doi-asserted-by": "crossref",
      "first-page": "2053",
      "DOI": "10.1242/dev.125.11.2053",
      "volume": "125",
      "year": "1998",
      "journal-title": "Development"
    },
    {
      "key": "2022110405475187800_BIB87",
      "doi-asserted-by": "crossref",
      "first-page": "9",
      "DOI": "10.1016/S0012-1606(03)00208-2",
      "volume": "259",
      "year": "2003",
      "journal-title": "Dev. Biol."
    },
    {
      "key": "2022110405475187800_BIB88",
      "doi-asserted-by": "crossref",
      "first-page": "e429",
      "DOI": "10.1371/journal.pbio.0020429",
      "volume": "2",
      "year": "2004",
      "journal-title": "PLoS Biol."
    },
    {
      "key": "2022110405475187800_BIB89",
      "doi-asserted-by": "crossref",
      "first-page": "4509",
      "DOI": "10.1523/JNEUROSCI.0455-06.2006",
      "volume": "26",
      "year": "2006",
      "journal-title": "J. Neurosci."
    },
    {
      "key": "2022110405475187800_BIB90",
      "year": "2003"
    },
    {
      "key": "2022110405475187800_BIB91",
      "doi-asserted-by": "crossref",
      "first-page": "385",
      "DOI": "10.1242/jeb.98.1.385",
      "volume": "98",
      "year": "1982",
      "journal-title": "J. Exp. Biol."
    },
    {
      "key": "2022110405475187800_BIB92",
      "doi-asserted-by": "crossref",
      "first-page": "6673",
      "DOI": "10.1523/JNEUROSCI.21-17-06673.2001",
      "volume": "21",
      "year": "2001",
      "journal-title": "J. Neurosci."
    },
    {
      "key": "2022110405475187800_BIB93",
      "doi-asserted-by": "crossref",
      "first-page": "1323",
      "DOI": "10.1016/0092-8674(93)90359-X",
      "volume": "73",
      "year": "1993",
      "journal-title": "Cell"
    },
    {
      "key": "2022110405475187800_BIB94",
      "doi-asserted-by": "crossref",
      "first-page": "271",
      "DOI": "10.1016/j.devcel.2005.07.004",
      "volume": "9",
      "year": "2005",
      "journal-title": "Dev. Cell"
    },
    {
      "key": "2022110405475187800_BIB95",
      "doi-asserted-by": "crossref",
      "first-page": "417",
      "DOI": "10.1101/gad.374406",
      "volume": "20",
      "year": "2006",
      "journal-title": "Genes Dev."
    },
    {
      "key": "2022110405475187800_BIB96",
      "doi-asserted-by": "crossref",
      "first-page": "283",
      "DOI": "10.1038/ng1314",
      "volume": "36",
      "year": "2004",
      "journal-title": "Nat. Genet."
    },
    {
      "key": "2022110405475187800_BIB97",
      "doi-asserted-by": "crossref",
      "first-page": "87",
      "DOI": "10.1016/S0739-7240(02)00148-0",
      "volume": "23",
      "year": "2002",
      "journal-title": "Domest. Anim. Endocrinol."
    },
    {
      "key": "2022110405475187800_BIB98",
      "doi-asserted-by": "crossref",
      "first-page": "471",
      "DOI": "10.1038/362471a0",
      "volume": "362",
      "year": "1993",
      "journal-title": "Nature"
    },
    {
      "key": "2022110405475187800_BIB99",
      "doi-asserted-by": "crossref",
      "first-page": "R145",
      "DOI": "10.1186/gb-2007-8-7-r145",
      "volume": "8",
      "year": "2007",
      "journal-title": "Genome Biol."
    },
    {
      "key": "2022110405475187800_BIB100",
      "doi-asserted-by": "crossref",
      "first-page": "756",
      "DOI": "10.2144/000112476",
      "volume": "42",
      "year": "2007",
      "journal-title": "Biotechniques"
    },
    {
      "key": "2022110405475187800_BIB101",
      "first-page": "805",
      "volume": "57",
      "year": "1973",
      "journal-title": "J. Exp. Biol."
    },
    {
      "key": "2022110405475187800_BIB102",
      "doi-asserted-by": "crossref",
      "first-page": "1404",
      "DOI": "10.1002/neu.480231005",
      "volume": "23",
      "year": "1992",
      "journal-title": "J. Neurobiol."
    },
    {
      "key": "2022110405475187800_BIB103",
      "doi-asserted-by": "crossref",
      "first-page": "87",
      "DOI": "10.1159/000111398",
      "volume": "18",
      "year": "1996",
      "journal-title": "Dev. Neurosci."
    },
    {
      "key": "2022110405475187800_BIB104",
      "doi-asserted-by": "crossref",
      "first-page": "219",
      "DOI": "10.1242/dev.120.1.219",
      "volume": "120",
      "year": "1994",
      "journal-title": "Development"
    },
    {
      "key": "2022110405475187800_BIB105",
      "doi-asserted-by": "crossref",
      "first-page": "229",
      "DOI": "10.1093/genetics/162.1.229",
      "volume": "162",
      "year": "2002",
      "journal-title": "Genetics"
    },
    {
      "key": "2022110405475187800_BIB106",
      "doi-asserted-by": "crossref",
      "first-page": "506",
      "DOI": "10.1046/j.1365-2826.2002.00798.x",
      "volume": "14",
      "year": "2002",
      "journal-title": "J. Neuroendocrinol."
    },
    {
      "key": "2022110405475187800_BIB107",
      "doi-asserted-by": "crossref",
      "first-page": "871",
      "DOI": "10.1016/S0896-6273(03)00295-2",
      "volume": "38",
      "year": "2003",
      "journal-title": "Neuron"
    },
    {
      "key": "2022110405475187800_BIB108",
      "doi-asserted-by": "crossref",
      "first-page": "421",
      "DOI": "10.1016/S0301-0082(03)00102-3",
      "volume": "70",
      "year": "2003",
      "journal-title": "Prog. Neurobiol."
    },
    {
      "key": "2022110405475187800_BIB109",
      "doi-asserted-by": "crossref",
      "first-page": "3631",
      "DOI": "10.1242/dev.01928",
      "volume": "132",
      "year": "2005",
      "journal-title": "Development"
    },
    {
      "key": "2022110405475187800_BIB110",
      "doi-asserted-by": "crossref",
      "first-page": "63",
      "DOI": "10.1016/0092-8674(92)90266-F",
      "volume": "71",
      "year": "1992",
      "journal-title": "Cell"
    },
    {
      "key": "2022110405475187800_BIB111",
      "doi-asserted-by": "crossref",
      "first-page": "476",
      "DOI": "10.1038/366476a0",
      "volume": "366",
      "year": "1993",
      "journal-title": "Nature"
    },
    {
      "key": "2022110405475187800_BIB112",
      "doi-asserted-by": "crossref",
      "first-page": "3483",
      "DOI": "10.1242/jeb.204.20.3483",
      "volume": "204",
      "year": "2001",
      "journal-title": "J. Exp. Biol."
    }
  ],
  "container-title": "Genetics",
  "original-title": [],
  "language": "en",
  "link": [
    {
      "URL": "https://academic.oup.com/genetics/article-pdf/178/2/883/46784036/genetics0883.pdf",
      "content-type": "application/pdf",
      "content-version": "vor",
      "intended-application": "syndication"
    },
    {
      "URL": "https://academic.oup.com/genetics/article-pdf/178/2/883/46784036/genetics0883.pdf",
      "content-type": "unspecified",
      "content-version": "vor",
      "intended-application": "similarity-checking"
    }
  ],
  "deposited": {
    "date-parts": [
      [
        2022,
        11,
        4
      ]
    ],
    "date-time": "2022-11-04T05:56:59Z",
    "timestamp": 1667541419000
  },
  "score": 1,
  "resource": {
    "primary": {
      "URL": "https://academic.oup.com/genetics/article/178/2/883/6062156"
    }
  },
  "subtitle": [],
  "short-title": [],
  "issued": {
    "date-parts": [
      [
        2008,
        2,
        1
      ]
    ]
  },
  "references-count": 112,
  "journal-issue": {
    "issue": "2",
    "published-online": {
      "date-parts": [
        [
          2008,
          2,
          1
        ]
      ]
    },
    "published-print": {
      "date-parts": [
        [
          2008,
          2,
          1
        ]
      ]
    }
  },
  "URL": "http://dx.doi.org/10.1534/genetics.107.082487",
  "relation": {},
  "ISSN": [
    "1943-2631"
  ],
  "subject": [],
  "published-other": {
    "date-parts": [
      [
        2008,
        2,
        1
      ]
    ]
  },
  "published": {
    "date-parts": [
      [
        2008,
        2,
        1
      ]
    ]
  }
}