Crossref journal-article
The Company of Biologists
Development (237)
Abstract

ABSTRACT Fibroblast growth factor (FGF) signaling has been implicated in the patterning of mesoderm and neural lineages during early vertebrate development. In the mouse, FGF receptor-1 (FGFR1) is expressed in an appropriate spatial and temporal manner to be orchestrating these functions. Mouse embryos homozygous for a mutated Fgfr1 allele (fgfr1Δtmk) die early in development, show abnormal growth and aberrant mesodermal patterning. We have performed a chimeric analysis to further study FGFR1 function in the morphogenesis and patterning of the mesodermal germ layer at gastrulation. At E9.5, fgfr1Δtmk/fgfr1Δtmk cells showed a marked deficiency in their ability to contribute to the extra-embryonic, cephalic, heart, axial and paraxial mesoderm, and to the endoderm of chimeric embryos. Analysis at earlier stages of development revealed that fgfr1Δtmk/fgfr1Δtmk cells accumulated within the primitive streak of chimeric embryos, and consequently failed to populate the anterior mesoderm and endodermal lineages at their inception. We suggest that the primary defect associated with the fgfr1Δtmk mutation is a deficiency in the ability of epiblast cells to traverse the primitive streak. fgfr1Δtmk/fgfr1Δtmk cells that accumulated within the primitive streak of chimeric embryos tended to form secondary neural tubes. These secondary neural tubes were entirely fgfr1Δtmk/fgfr1Δtmk cell derived. The adoption of ectopic neural fate suggests that normal morphogenetic movement through the streak is essential not only for proper mesodermal patterning but also for correct determination of mesodermal/neurectodermal cell fates.

Bibliography

Ciruna, B. G., Schwartz, L., Harpal, K., Yamaguchi, T. P., & Rossant, J. (1997). Chimeric analysis of fibroblast growth factor receptor-1 (Fgfr1) function: a role for FGFR1 in morphogenetic movement through the primitive streak. Development, 124(14), 2829–2841.

Authors 5
  1. Brian G. Ciruna (first)
  2. Lois Schwartz (additional)
  3. Kendraprasad Harpal (additional)
  4. Terry P. Yamaguchi (additional)
  5. Janet Rossant (additional)
References 63 Referenced 275
  1. 10.1016/0092-8674(91)90616-7 / Cell / Expression of a dominant negative mutant of the FGF receptor disrupts mesoderm formation in Xenopus embryos by Amaya (1991)
  2. 10.1242/dev.118.2.477 / Development / FGF signalling in the early specification of mesoderm in Xenopus by Amaya (1993)
  3. {'key': '2025021404084223700_DEVELOP_124_14_2829C3', 'first-page': '61', 'article-title': 'Use of chimeras to study gene function in mesodermal tissues during gastrulation and early organogenesis', 'volume': '165', 'author': 'Beddington', 'year': '1992', 'journal-title': 'Ciba Found. Symp'} / Ciba Found. Symp / Use of chimeras to study gene function in mesodermal tissues during gastrulation and early organogenesis by Beddington (1992)
  4. 10.1242/dev.120.3.613 / Development / Induction of a second neural axis by the mouse node by Beddington (1994)
  5. 10.1101/gad.10.23.2993 / Genes Dev / Heartless, a Drosophila FGF receptor homolog, is essential for cell migration and establishment of several mesodermal lineages by Beiman (1996)
  6. 10.1016/0014-4827(92)90283-E / Exp. Cell Res / E-cadherin expression during the acidic FGF-induced dispersion of a rat bladder carcinoma cell line by Boyer (1992)
  7. 10.1242/dev.118.3.829 / Development / The role of Ecadherin and integrins in mesoderm differentiation and migration at the mammalian primitive streak by Burdsal (1993)
  8. 10.1242/dev.116.4.1123 / Development / Mox-1 and Mox-2 define a novel homeobox gene subfamily and are differentially expressed during early mesodermal patterning in mouse embryos by Candia (1992)
  9. 10.1002/tera.1420340314 / Teratology / Diplomyelia: caudal duplication of the neural tube in mice by Cogliatti (1986)
  10. 10.1242/dev.122.2.509 / Development / A comparison of the properties of Sox-3 with Sry and two related genes, Sox-1 and Sox-2 by Collignon (1996)
  11. 10.1242/dev.116.2.357 / Development / Exogenous retinoic acid rapidly induces anterior ectopic expression of murine Hox-2 genes in vivo by Conlon (1992)
  12. 10.1242/dev.121.12.4349 / Development / Caudalization of neural fate by tissue recombination and bFGF by Cox (1995)
  13. 10.1016/0012-1606(86)90056-4 / Dev. Biol / Developmentally regulated expression of the cell-cell adhesion glycoprotein cell-CAM 120/80 in peri-implantation mouse embryos and extraembryonic membranes by Damjanov (1986)
  14. 10.1101/gad.8.24.3045 / Genes Dev / Murine FGFR-1 is required for early postimplantation growth and axial organization by Deng (1994)
  15. 10.1016/0092-8674(95)90101-9 / Cell / An FGF receptor signaling pathway is required for the normal cell migrations of the sex myoblasts in C. elegans hermaphrodites by DeVore (1995)
  16. 10.1016/0092-8674(93)90627-3 / Cell / Sonic hedgehog, a member of a family of putative signaling molecules, is implicated in the regulation of CNS polarity by Echelard (1993)
  17. 10.1126/science.7809630 / Science / Requirement of FGF-4 for postimplantation mouse development by Feldman (1995)
  18. 10.1101/gad.5.9.1513 / Genes Dev / Promoter traps in embryonic stem cells: a genetic screen to identify and mutate developmental genes in mice by Friedrich (1991)
  19. {'key': '2025021404084223700_DEVELOP_124_14_2829C19', 'first-page': '1989', 'article-title': 'Mesodermal defect in late phase of gastrulation by a targeted mutation of focal adhesion kinase, FAK', 'volume': '11', 'author': 'Furuta', 'year': '1995', 'journal-title': 'Oncogene'} / Oncogene / Mesodermal defect in late phase of gastrulation by a targeted mutation of focal adhesion kinase, FAK by Furuta (1995)
  20. 10.1242/dev.119.4.1079 / Development / Defects in mesoderm, neural tube and vascular development in mouse embryos lacking fibronectin by George (1993)
  21. 10.1101/gad.10.23.3003 / Genes Dev / heartless encodes a fibroblast growth factor receptor (DFR1/DFGF-R2) involved in the directional migration of early mesodermal cells in the Drosophila embryo by Gisselbrecht (1996)
  22. 10.1096/fasebj.6.15.1464370 / Faseb J / Complexity of FGF receptors: genetic basis for structural diversity and functional specificity by Givol (1992)
  23. 10.1002/j.1460-2075.1991.tb08054.x / EMBO J / Pax-3, a novel murine DNA binding protein expressed during early neurogenesis by Goulding (1991)
  24. 10.1101/gad.10.3.313 / Genes Dev / Analysis of the vestigial tail mutation demonstrates that Wnt-3a gene dosage regulates mouse axial development by Greco (1996)
  25. 10.1002/bies.950180807 / BioEssays / Promiscuity of fibroblast growth factor receptors by Green (1996)
  26. {'key': '2025021404084223700_DEVELOP_124_14_2829C26', 'first-page': '207', 'article-title': 'A re-examination of two skeletal mutants of the mouse, vestigial-tail (vt) and congenital hydrocephalus (ch)', 'volume': '31', 'author': 'Gruneberg', 'year': '1974', 'journal-title': 'J. Embryol. Exp. Morphol'} / J. Embryol. Exp. Morphol / A re-examination of two skeletal mutants of the mouse, vestigial-tail (vt) and congenital hydrocephalus (ch) by Gruneberg (1974)
  27. 10.1242/dev.112.2.397 / Development / Expression of the fibroblast growth factor5 gene in the mouse embryo by Haub (1991)
  28. 10.1242/dev.112.2.407 / Development / mRNA localization studies suggest that murine FGF-5 plays a role in gastrulation by Hebert (1991)
  29. 10.1016/0092-8674(94)90276-3 / Cell / FGF5 as a regulator of the hair growth cycle: evidence from targeted and spontaneous mutations by Hebert (1994)
  30. 10.1016/S0092-8674(00)81853-X / Cell / Vertebrate embryonic cells will become nerve cells unless told otherwise by Hemmati-Brivanlou (1997)
  31. 10.1242/dev.113.3.913 / Development / Expression pattern of the Brachyury gene in wholemount TWis/TWis mutant embryos by Herrmann (1991)
  32. {'key': '2025021404084223700_DEVELOP_124_14_2829C32', 'volume-title': 'Manipulating the Mouse Embryo. A Laboratory Manual', 'author': 'Hogan', 'year': '1994', 'edition': 'Second'} / Manipulating the Mouse Embryo. A Laboratory Manual by Hogan (1994)
  33. 10.1002/j.1460-2075.1994.tb06769.x / EMBO J / eFGF regulates Xbra expression during Xenopus gastrulation by Isaacs (1994)
  34. 10.1242/dev.121.9.3121 / Development / bFGF as a possible morphogen for the anteroposterior axis of the central nervous system in Xenopus by Kengaku (1995)
  35. 10.1016/0092-8674(87)90110-3 / Cell / Synergistic induction of mesoderm by FGF and TGF-beta and the identification of an mRNA coding for FGF in the early Xenopus embryo by Kimelman (1987)
  36. 10.1242/dev.122.10.3173 / Development / Transgenic Xenopus embryos from sperm nuclear transplantations reveal FGF signaling requirements during gastrulation by Kroll (1996)
  37. 10.1242/dev.121.11.3627 / Development / Fibroblast growth factor is a direct neural inducer, which combined with noggin generates anterior-posterior neural pattern by Lamb (1995)
  38. 10.1242/dev.113.3.891 / Development / Clonal analysis of epiblast fate during germ layer formation in the mouse embryo by Lawson (1991)
  39. 10.1242/dev.117.1.13 / Development / Mice homozygous for a targeted disruption of the proto-oncogene int-2 have developmental defects in the tail and inner ear by Mansour (1993)
  40. 10.1038/ng1096-223 / Nat. Genet / Selective ablation of differentiated cells permits isolation of embryonic stem cell lines from murine embryos with a nonpermissive genetic background by McWhir (1996)
  41. 10.1073/pnas.90.18.8424 / Proc. Natl. Acad. Sci. USA / Derivation of completely cell culture-derived mice from earlypassage embryonic stem cells by Nagy (1993)
  42. 10.1242/dev.122.9.2933 / Development / Evidence in the mouse for self-renewing stem cells in the formation of a segmented longitudinal structure, the myotome by Nicolas (1996)
  43. 10.1242/dev.114.3.755 / Development / Fgf-4 expression during gastrulation, myogenesis, limb and tooth development in the mouse by Niswander (1992)
  44. 10.1074/jbc.271.25.15292 / J. Biol. Chem / Receptor specificity of the fibroblast growth factor family by Ornitz (1996)
  45. 10.1242/dev.113.4.1419 / Development / Developmental expression of two murine fibroblast growth factor receptors, flg and bek by Orr-Urtreger (1991)
  46. 10.1002/dvg.1020170104 / Dev. Genet / Regionalisation of cell fate and morphogenetic movement of the mesoderm during mouse gastrulation by Parameswaran (1995)
  47. 10.1242/dev.106.1.79 / Development / Mesoderm-inducing properties of INT-2 and kFGF: two oncogeneencoded growth factors related to FGF by Paterno (1989)
  48. 10.1242/dev.122.12.3881 / Development / eFGF, Xcad3 and Hox genes form a molecular pathway that establishes the anteroposterior axis in Xenopus by Pownall (1996)
  49. 10.1101/gad.8.4.428 / Genes Dev / Elucidation of the role of breathless, a Drosophila FGF receptor homolog, in tracheal cell migration by Reichman-Fried (1994)
  50. 10.1242/dev.107.Supplement.141 / Development / The role of fibroblast growth factor in early Xenopus development by Slack (1989)
  51. 10.1242/dev.116.4.1033 / Development / Isolation of Sna, a mouse gene homologous to the Drosophila genes snail and escargot: its expression pattern suggests multiple roles during postimplantation development by Smith (1992)
  52. 10.1101/gad.8.2.174 / Genes Dev / Wnt-3a regulates somite and tailbud formation in the mouse embryo by Takada (1994)
  53. 10.1242/dev.99.1.109 / Development / The formation of mesodermal tissues in the mouse embryo during gastrulation and early organogenesis by Tam (1987)
  54. 10.1242/dev.107.1.55 / Development / Regionalisation of the mouse embryonic ectoderm: allocation of prospective ectodermal tissues during gastrulation by Tam (1989)
  55. 10.1007/BF00707309 / Anat. Embryol / Development of rib-vertebrae: a new mutation in the house mouse with accessory caudal duplications by Theiler (1985)
  56. 10.1242/dev.113.4.1435 / Development / Pax-6, a murine paired box gene, is expressed in the developing CNS by Walther (1991)
  57. 10.1002/j.1460-2075.1988.tb02864.x / EMBO J / Expression of the FGF-related proto-oncogene int-2 during gastrulation and neurulation in the mouse by Wilkinson (1988)
  58. 10.1242/dev.117.4.1321 / Development / Chimeric analysis of T (Brachyury) gene function by Wilson (1993)
  59. 10.1242/dev.121.3.877 / Development / The T gene is necessary for normal mesodermal morphogenetic cell movements during gastrulation by Wilson (1995)
  60. 10.1016/0012-1606(91)90086-I / Dev. Biol / The M-twist gene of Mus is expressed in subsets of mesodermal cells and is closely related to the Xenopus X-twi and the Drosophila twist genes by Wolf (1991)
  61. 10.1016/0012-1606(92)90157-C / Dev. Biol / Expression of the fibroblast growth factor receptor FGFR-1/flg during gastrulation and segmentation in the mouse embryo by Yamaguchi (1992)
  62. 10.1101/gad.8.24.3032 / Genes Dev / fgfr1 is required for embryonic growth and mesodermal patterning during mouse gastrulation by Yamaguchi (1994)
  63. 10.1006/dbio.1997.8502 / Dev. Biol / Evidence that absence of Wnt-3a signaling promotes neuralization instead of paraxial mesoderm development in the mouse by Yoshikawa (1997)
Dates
Type When
Created 4 years, 4 months ago (April 23, 2021, 3:10 p.m.)
Deposited 6 months, 2 weeks ago (Feb. 13, 2025, 11:09 p.m.)
Indexed 3 months, 1 week ago (May 22, 2025, 2:23 p.m.)
Issued 28 years, 1 month ago (July 15, 1997)
Published 28 years, 1 month ago (July 15, 1997)
Published Online 28 years, 1 month ago (July 15, 1997)
Published Print 28 years, 1 month ago (July 15, 1997)
Funders 0

None

@article{Ciruna_1997, title={Chimeric analysis of fibroblast growth factor receptor-1 (Fgfr1) function: a role for FGFR1 in morphogenetic movement through the primitive streak}, volume={124}, ISSN={1477-9129}, url={http://dx.doi.org/10.1242/dev.124.14.2829}, DOI={10.1242/dev.124.14.2829}, number={14}, journal={Development}, publisher={The Company of Biologists}, author={Ciruna, Brian G. and Schwartz, Lois and Harpal, Kendraprasad and Yamaguchi, Terry P. and Rossant, Janet}, year={1997}, month=jul, pages={2829–2841} }