The PDGFα receptor is required for neural crest cell development and for normal patterning of the somites

Development (Cambridge) - Tập 124 Số 14 - Trang 2691-2700 - 1997
Philippe Soriano1
1Division of Basic Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Seattle, WA 98109 USA

Tóm tắt

ABSTRACT Platelet-derived growth factors (PDGFs) have been implicated in the control of cell proliferation, survival and migration. Patch mutant mice harbor a deletion including the PDGFα receptor gene and exhibit defects of neural crest origin which affect pigmentation in heterozygotes and cranial bones in homozygotes. To verify the role of the PDGFαR gene during development, mice carrying a targeted null mutation were generated. No pigmentation phenotype was observed in heterozygotes. Homozygotes die during embryonic development and exhibit incomplete cephalic closure similar to that observed in a subset of Patch mutants. In addition, increased apoptosis was observed on pathways followed by migrating neural crest cells. However, alterations in mutant vertebrae, ribs and sternum were also observed, which appear to stem from a deficiency in myotome formation. These results indicate that PDGFs may exert their functions during early embryogenesis by affecting cell survival and patterning.

Từ khóa


Tài liệu tham khảo

Ataliotis, 1995, PDGF signalling is required for gastrulation of Xenopus laevis, Development, 121, 3099, 10.1242/dev.121.9.3099

Baldwin, 1994, Platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31): alternatively spliced, functionally distinct isoforms expressed during mammalian cardiovascular development, Development, 120, 2539, 10.1242/dev.120.9.2539

Balling, 1988, Undulated, a mutation affecting the development of the mouse skeleton, has a point mutation in the paired box of Pax1, Cell, 55, 531, 10.1016/0092-8674(88)90039-6

Barres, 1992, Cell death and control of cell survival in the oligodendrocyte lineage, Cell, 70, 31, 10.1016/0092-8674(92)90531-G

Boström, 1996, PDGF-A signaling is a critical event in lung alveolar myofibroblast development and alveogenesis, Cell, 85, 863, 10.1016/S0092-8674(00)81270-2

Braun, 1992, Targeted inactivation of the muscle gene Myf-5 results in abnormal rib development and perinatal death, Cell, 71, 369, 10.1016/0092-8674(92)90507-9

Bronner-Fraser, 1995, Origins and developmental potential of the neural crest, Exp. Cell Res, 218, 405, 10.1006/excr.1995.1173

Brunkow, 1995, A 1.8Mb YAC contig spanning three members of the receptor tyrosine kinase gene family (Pdgfra, Kit, and Flk1) on mouse chromosome 5, Genomics, 25, 421432, 10.1016/0888-7543(95)80042-K

Candia, 1992, Mox-1 and Mox-2 define a novel homeobox gene subfamily and are differentially expressed during early mesodermal patterning in mouse embryos, Development, 116, 1123, 10.1242/dev.116.4.1123

Chabot, 1988, The proto-oncogene c-kit encoding a transmembrane tyrosine kinase receptor maps to the mouse W locus, Nature, 335, 88, 10.1038/335088a0

Claesson-Welsh, 1994, Platelet-derived growth factor receptor signals, J. Biol. Chem, 269, 32023, 10.1016/S0021-9258(18)31591-6

Conlon, 1995, Notch1 is required for the coordinate segmentation of somites, Development, 121, 1533, 10.1242/dev.121.5.1533

Dickinson, 1995, Dorsalization of the neural tube by the non-neural ectoderm, Development, 121, 2099, 10.1242/dev.121.7.2099

Duttlinger, 1995, The Wsh and Ph mutations affect the c-kit expression profile: c-kit misexpression in embryogenesis impairs melanogenesis in Wsh and Ph mutant mice, Proc. Natl. Acad. Sci. USA, 92, 3754, 10.1073/pnas.92.9.3754

Fan, 1994, Patterning of mammalian somites by surface ectoderm and notochord: evidence for sclerotome induction by a hedgehog homolog, Cell, 79, 1175, 10.1016/0092-8674(94)90009-4

Geissler, 1988, The dominantWhite Spotting (W) locus of the mouse encodes the c-kit proto-oncogene, Cell, 55, 185, 10.1016/0092-8674(88)90020-7

Grass, 1996, Alterations in somite patterning of myf-5 deficient mice: a possible role for FGF-4 and FGF-6, Development, 122, 141, 10.1242/dev.122.1.141

Grüneberg, 1963, The Pathology of Development

Grüneberg, 1960, Two closely linked genes in the mouse, Genet. Res, 1, 69, 10.1017/S0016672300000094

Helwig, 1995, Interaction between undulated and Patch leads to an extreme form of spina bifida in double-mutant mice, Nature Gen, 11, 60, 10.1038/ng0995-60

Hogan, 1994, Manipulating the Mouse Embryo: a Laboratory Manual

Imamoto, 1993, Disruption of the csk gene, encoding a negative regulator of Src family tyrosine kinases, leads to neural tube defects and embryonic lethality in mice, Cell, 73, 1117, 10.1016/0092-8674(93)90641-3

Jeffs, 1992, Cell death in cranial neural crest development, Anat. Embryol, 185, 583, 10.1007/BF00185617

Jeffs, 1992, A segmented pattern of cell death during development of the chick embryo, Anat. Embryol, 185, 589, 10.1007/BF00185618

Kazlauskas, 1994, Receptor tyrosine kinases and their targets, Curr. Opin. Genet. Dev, 4, 5, 10.1016/0959-437X(94)90085-X

Koyama, 1992, Regulatory effects of platelet-derived growth factor AA homodimer on migration of vascular smooth muscle cells, J. Biol. Chem, 267, 22806, 10.1016/S0021-9258(18)50019-3

Le Douarin, 1993, Patterning of neural crest derivatives in the avian embryo: in vivo and in vitro studies, Dev. Biology, 159, 24, 10.1006/dbio.1993.1219

Levéen, 1994, Mice deficient for PDGF B show renal, cardiovascular, and hematological abnormalities, Genes Dev, 8, 1875, 10.1101/gad.8.16.1875

Liem, 1995, Dorsal differentiation of neural plate cells induced by BMP-mediated signals from epidermal ectoderm, Cell, 82, 969, 10.1016/0092-8674(95)90276-7

Morrison-Graham, 1992, A PDGF receptor mutation in the mouse (Patch) perturbs the development of a non-neuronal subset of neural crest-derived cells, Development, 115, 133, 10.1242/dev.115.1.133

Nagle, 1994, Structural analysis of chromosomal rearrangements associated with the developmental mutations Ph, W19H, and Rw on mouse chromosome 5, Proc. Natl. Acad. Sci. USA, 91, 7237, 10.1073/pnas.91.15.7237

Olson, 1996, Know your neighbors: three phenotypes in null mutants of the myogenic bHLH gene MRF4, Cell, 85, 1, 10.1016/S0092-8674(00)81073-9

Orr-Urtreger, 1992, Developmental expression of the α receptor for platelet-derived growth factor, which is deleted in the embryonic lethal Patch mutation, Development, 115, 289, 10.1242/dev.115.1.289

Orr-Urtreger, 1992, Platelet-derived growth factor-A and its receptor are expressed in separate, but adjacent cell layers of the mouse embryo, Development, 115, 1045, 10.1242/dev.115.4.1045

Payne, 1997, Spina bifida occulta in homozygous Patch mouse embryos, Developmental Dyn, 209, 105, 10.1002/(SICI)1097-0177(199705)209:1<105::AID-AJA10>3.0.CO;2-0

Raff, 1992, Social controls on cell survival and cell death, Nature, 356, 397, 10.1038/356397a0

Raff, 1993, Programmed cell death and the control of cell survival: lessons from the nervous system, Science, 262, 695, 10.1126/science.8235590

Ross, 1986, The biology of platelet-derived growth factor, Cell, 46, 155, 10.1016/0092-8674(86)90733-6

Schatteman, 1992, Regulation and role of PDGF receptor αsubunit expression during embryogenesis, Development, 115, 123, 10.1242/dev.115.1.123

Seifert, 1989, Two different subunits associate to create isoform-specific platelet-derived growth factor receptors, J. Biol. Chem, 264, 8771, 10.1016/S0021-9258(18)81860-9

Selleck, 1995, Origins of the avian neural crest: the role of neural plate-epidermal interactions, Development, 121, 525538, 10.1242/dev.121.2.525

Smith, 1991, Mouse platelet-derived growth factor receptor α gene is deleted in W19H and patch mutations on chromosome 5, Proc. Natl. Acad. Sci. USA, 88, 4811, 10.1073/pnas.88.11.4811

Soriano, 1994, Abnormal kidney development and hematological disorders in PDGF β-receptor mutant mice, Genes Dev, 8, 1888, 10.1101/gad.8.16.1888

Soriano, 1991, Targeted disruption of the c-src proto-oncogene leads to ospeopetrosis in mice, Cell, 64, 693, 10.1016/0092-8674(91)90499-O

Spence, 1996, The dorsal neural tube organizes the dermomyotome and induces axial myocytes in the avian embryo, Development, 122, 231, 10.1242/dev.122.1.231

Stephenson, 1991, Platelet-derived growth factor receptor α-subunit gene (Pdgfra) is deleted in the mouse patch (Ph) mutation, Proc. Natl. Acad. Sci. USA, 88, 6, 10.1073/pnas.88.1.6

Symes, 1996, Embryonic mesoderm cells spread in response to platelet-derived growth factor and signaling by phosphatidylinositol 3-kinase, Proc. Natl. Acad. Sci. USA, 93, 9641, 10.1073/pnas.93.18.9641

Truslove, 1977, A new allele at the patch locus in the mouse, Genet. Res, 29, 183, 10.1017/S0016672300017249

Wang, 1994, Platelet-derived growth factor α receptor gene expression: isolation and characterization of the promoter and upstream regulatory elements, Proc. Natl. Acad. Sci. USA, 91, 7061, 10.1073/pnas.91.15.7061

Wehrle-Haller, 1996, Ectopic c-kit expression affects the fate of melanocyte precursors in Patch mutant embryos, Dev. Biol, 177, 463, 10.1006/dbio.1996.0178

Yu, 1994, Structural coincidence of αPDGFR epitopes binding to plateletderived growth factor AA and a potent neutralizing monoclonal antibody, J. Biol. Chem, 269, 10668, 10.1016/S0021-9258(17)34111-X