Apoptosis in mouse embryos: Elevated levels in pregastrulae and in the distal anterior region of gastrulae of normal and mutant mice

The pattern of apoptotic cell death has been surveyed in prestreak and primitive streak embryos of four strains of mice and in three mutants affecting gastrulation. In C57BL/ 6 embryos, a high level of cell death occurs in the early egg cylinder stage at embryonic day 5 (E5) to E5.5. In all strains, cell death is elevated shortly before gastrulation, but the level varies four‐ to fivefold among strains. During gastrulation, cell death declines but is relatively more abundant in the distal and distal anterior regions. Early streak embryos cultured in media with reduced levels of growth factors show increased cell death mainly in the distal region. In three mutants with disturbed function of the proximal visceral endoderm and/ or primitive streak, cell death is increased, and the regional pattern seen in normal embryos is intensified. The results strongly suggest that the proximal visceral endoderm and primitive streak region are the principal sites of synthesis of growth factors promoting cell survival. We conclude that localized growth factor supply has an important role in regulating the size of the embryo and of embryonic regions. Dev. Dyn. 1998;213:293–308. © 1998 Wiley‐Liss, Inc.

[1]  K. Manova,et al.  The amn gene product is required in extraembryonic tissues for the generation of middle primitive streak derivatives. , 1998, Developmental biology.

[2]  M. Stoffel,et al.  The maturity-onset diabetes of the young (MODY1) transcription factor HNF4alpha regulates expression of genes required for glucose transport and metabolism. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[3]  T. Bouwmeester,et al.  Cerberus-like is a secreted factor with neuralizing activity expressed in the anterior primitive endoderm of the mouse gastrula , 1997, Mechanisms of Development.

[4]  R. Behringer,et al.  Mouse gastrulation: the formation of a mammalian body plan , 1997, Mechanisms of Development.

[5]  M. Raff,et al.  Programmed Cell Death in Animal Development , 1997, Cell.

[6]  A. S. French,et al.  Patterns of cell death during gastrulation in chick and mouse embryos , 1997, Anatomy and Embryology.

[7]  A. Nagy,et al.  Murine gastrulation requires HNF-4 regulated gene expression in the visceral endoderm: tetraploid rescue of Hnf-4(-/-) embryos. , 1997, Development.

[8]  D. Gilbert,et al.  A candidate gene for the amnionless gastrulation stage mouse mutation encodes a TRAF-related protein. , 1996, Developmental biology.

[9]  R. Behringer,et al.  Bmpr encodes a type I bone morphogenetic protein receptor that is essential for gastrulation during mouse embryogenesis. , 1995, Genes & development.

[10]  E. Coucouvanis,et al.  Signals for death and survival: A two-step mechanism for cavitation in the vertebrate embryo , 1995, Cell.

[11]  Virginia E. Papaioannou,et al.  Increased apoptosis and early embryonic lethality in mice nullizygous for the Huntington's disease gene homologue , 1995, Nature Genetics.

[12]  G. Martin,et al.  The mouse Fgf8 gene encodes a family of polypeptides and is expressed in regions that direct outgrowth and patterning in the developing embryo. , 1995, Development.

[13]  J. Darnell,et al.  Disruption of the HNF-4 gene, expressed in visceral endoderm, leads to cell death in embryonic ectoderm and impaired gastrulation of mouse embryos. , 1994, Genes & development.

[14]  Thomas M. Jessell,et al.  The winged-helix transcription factor HNF-3β is required for notochord development in the mouse embryo , 1994, Cell.

[15]  J. Rossant,et al.  HNF-3β is essential for node and notochord formation in mouse development , 1994, Cell.

[16]  J. Darnell,et al.  Expression of transcription factor HNF-4 in the extraembryonic endoderm, gut, and nephrogenic tissue of the developing mouse embryo: HNF-4 is a marker for primary endoderm in the implanting blastocyst. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[17]  F. Conlon,et al.  A primary requirement for nodal in the formation and maintenance of the primitive streak in the mouse. , 1994, Development.

[18]  J. Rossant,et al.  The formation and maintenance of the definitive endoderm lineage in the mouse: involvement of HNF3/forkhead proteins. , 1993, Development.

[19]  J. Darnell,et al.  Sequential expression of HNF-3β and HNF-3α by embryonic organizing centers: the dorsal lip/node, notochord and floor plate , 1993, Mechanisms of Development.

[20]  K. Kaestner,et al.  Postimplantation expression patterns indicate a role for the mouse forkhead/HNF-3 alpha, beta and gamma genes in determination of the definitive endoderm, chordamesoderm and neuroectoderm. , 1993, Development.

[21]  T. Davies,et al.  Staging of gastrulating mouse embryos by morphological landmarks in the dissecting microscope. , 1993, Development.

[22]  M. Raff,et al.  Large-scale normal cell death in the developing rat kidney and its reduction by epidermal growth factor. , 1993, Development.

[23]  B. Hogan,et al.  Differential expression of multiple fork head related genes during gastrulation and axial pattern formation in the mouse embryo. , 1993, Development.

[24]  Z. Werb,et al.  Characterization of the unusually rapid cell cycles during rat gastrulation. , 1993, Development.

[25]  S. Ben‐Sasson,et al.  Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation , 1992, The Journal of cell biology.

[26]  G. Martin,et al.  Fgf-4 expression during gastrulation, myogenesis, limb and tooth development in the mouse. , 1992, Development.

[27]  R. Pedersen,et al.  Clonal analysis of epiblast fate during germ layer formation in the mouse embryo. , 1991, Development.

[28]  W. Jollie Development, morphology, and function of the yolk-sac placenta of laboratory rodents. , 1990, Teratology.

[29]  P. Tam Regionalisation of the mouse embryonic ectoderm: allocation of prospective ectodermal tissues during gastrulation. , 1989, Development.

[30]  J. Heath,et al.  Serum‐free culture of PC13 murine embryonal carcinoma cells , 1983, Journal of cellular physiology.

[31]  M. Snow Autonomous development of parts isolated from primitive-streak-stage mouse embryos. Is development clonal? , 1981, Journal of embryology and experimental morphology.

[32]  R. Poelmann Differential mitosis and degeneration patterns in relation to the alterations in the shape of the embryonic ectoderm of early post-implantation mouse embryos. , 1980, Journal of embryology and experimental morphology.

[33]  J. Haar,et al.  Fine structural differentiation of germ layers in the mouse at the time of mesoderm formation , 1979, The Anatomical record.

[34]  D. Bennett,et al.  Gastrulation in the mouse: assessment of cell populations in the epiblast of tw18/tw18 embryos. , 1978, Journal of embryology and experimental morphology.

[35]  E. Adamson,et al.  Localization and synthesis of alphafoetoprotein in post-implantation mouse embryos. , 1978, Journal of embryology and experimental morphology.

[36]  M. Snow Gastrulation in the mouse: Growth and regionalization of the epiblast , 1977 .

[37]  M. Abercrombie Estimation of nuclear population from microtome sections , 1946, The Anatomical record.

[38]  J. Rossant,et al.  The tumor suppressor gene Smad4/Dpc4 is required for gastrulation and later for anterior development of the mouse embryo. , 1998, Genes & development.

[39]  K. Kaestner,et al.  Postimplantation expression patterns indicate a role for the mouse forkhead /HNF-3 , and genes in determination of the definitive endoderm, chordamesoderm and neuroectoderm , 1996 .

[40]  P. Tam,et al.  Neuroectodermal fate of epiblast cells in the distal region of the mouse egg cylinder: implication for body plan organization during early embryogenesis. , 1995, Development.

[41]  J. Smith,et al.  Control of vertebrate gastrulation: inducing signals and responding genes. , 1993, Current opinion in genetics & development.

[42]  P. Tam,et al.  Isolation and culture of whole postimplantation embryos and germ layer derivatives. , 1993, Methods in enzymology.