PMID- 8681797 OWN - NLM STAT- MEDLINE DCOM- 19960822 LR - 20220318 IS - 0950-1991 (Print) IS - 0950-1991 (Linking) VI - 122 IP - 7 DP - 1996 Jul TI - Expression of the met receptor tyrosine kinase in muscle progenitor cells in somites and limbs is absent in Splotch mice. PG - 2163-71 AB - Hepatocyte growth factor/scatter factor (HGF/SF) stimulates proliferation, dissociation, migration and morphogenesis of cells in culture. To investigate a possible role for HGF/SF and its receptor, the Met tyrosine kinase, in embryonic development, we have analyzed their expression in mouse embryos from day 7.5 of gestation by whole-mount in situ hybridization. Met expression is first detected in the ventral portion of somites at day 9.25 of gestation (22 somite embryo) at the level of fore limb buds. As somites mature, met expression is detected in caudal somites, and is confined to the lateral and media] tips of the dermomyotome and dermomyotome/myotome respectively. In contrast, HGF/SF is expressed exclusively in the mesodermal core of the limb bud. As the dermomyotome elongates ventrolaterally, the met-expressing cells at the lateral tip appear to detach from the somite, invade the limb bud and localize at the dorsal and ventral limb sides in close proximity to HGF/SF-expressing cells. At later stages, both met- and HGF/SF-expressing cells appear to migrate distally and localize to the digit forming area of the developing hand plate. Met expression in the lateral dermomyotome and limb bud coincides with expression of Pax-3, a marker for migrating muscle precursor cells in the somite and limb. Splotch-2H and Splotch-delayed mice, which harbor mutations in Pax-3, show major disruptions in early limb muscle development. Significantly, no met-expressing cells were observed in the limbs of homozygous Splotch-2H and Splotch-delayed animals, whereas HGF/SF expression was not affected. The restricted expression of met to a sub-population of Pax-3-expressing cells in the lateral tip of the dermomyotome, demonstrates that met represents a unique molecular marker for this migratory cell population. From these observations, together with the biological activities of HGF/SF, we propose that in homozygous Splotch embryos the failure of muscle precursors to migrate into and populate the limb bud results from a loss of met expression in the cells at the ventrolateral edge of the somitic dermomyotome. FAU - Yang, X M AU - Yang XM AD - Molecular Oncology Group, Royal Victoria Hospital, Montreal, Quebec, Canada. FAU - Vogan, K AU - Vogan K FAU - Gros, P AU - Gros P FAU - Park, M AU - Park M LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Development JT - Development (Cambridge, England) JID - 8701744 RN - 0 (DNA-Binding Proteins) RN - 0 (PAX3 Transcription Factor) RN - 0 (Paired Box Transcription Factors) RN - 0 (RNA, Complementary) RN - 0 (Transcription Factors) RN - 138016-91-8 (Pax3 protein, mouse) RN - 63231-63-0 (RNA) RN - 67256-21-7 (Hepatocyte Growth Factor) RN - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases) RN - EC 2.7.7.49 (RNA-Directed DNA Polymerase) SB - IM MH - Animals MH - Base Sequence MH - DNA-Binding Proteins/analysis MH - Female MH - Forelimb/metabolism MH - Gene Expression Regulation, Developmental MH - Hepatocyte Growth Factor/*analysis/physiology MH - Hindlimb/metabolism MH - In Situ Hybridization MH - Limb Buds/cytology/*metabolism MH - Mesoderm/*metabolism MH - Mice MH - Mice, Neurologic Mutants MH - Molecular Sequence Data MH - Muscles/cytology/*embryology MH - PAX3 Transcription Factor MH - Paired Box Transcription Factors MH - Polymerase Chain Reaction MH - Pregnancy MH - RNA/isolation & purification MH - RNA, Complementary MH - RNA-Directed DNA Polymerase MH - Receptor Protein-Tyrosine Kinases/*analysis/physiology MH - Stem Cells/*metabolism MH - *Transcription Factors EDAT- 1996/07/01 00:00 MHDA- 1996/07/01 00:01 CRDT- 1996/07/01 00:00 PHST- 1996/07/01 00:00 [pubmed] PHST- 1996/07/01 00:01 [medline] PHST- 1996/07/01 00:00 [entrez] AID - 10.1242/dev.122.7.2163 [doi] PST - ppublish SO - Development. 1996 Jul;122(7):2163-71. doi: 10.1242/dev.122.7.2163.