title: Synergistic interactions between bFGF and a TGF-beta family member may mediate myogenic signals from the neural tube.
abstract: Development of the myotome within somites depends on unknown signals from the neural tube. The present study tested the ability of basic fibroblast growth factor (bFGF), transforming growth factor-beta1 (TGF-beta1) and dorsalin-1 (dsl-1) to promote myogenesis in stage 10-14 chick paraxial mesoderm utilizing 72 hour explant cultures. Each of these factors alone and the combination of bFGF with dsl-1 had limited to no myogenic-promoting activity, but the combination of bFGF with TGF-beta1 demonstrated a potent dose-dependent effect. In addition, bFGF enhanced the survival/proliferation of somite cells. 98% of stage 10-11 caudal segmental plate explants treated with bFGF plus TGF-beta1, exhibited myosin heavy chain (MHC)-positive cells (avg.=60 per explant), whereas only 15% of similarly treated somites responded with an average of 5 MHC-positive cells. Thus at stage 10-11, there are rostrocaudal differences in myogenic responsiveness with the caudal (more 'immature') paraxial mesoderm being more myogenically responsive to these factors than are somites. It was also discovered that 17% of stage 10-11 caudal segmental plate explants exhibited several MHC-positive cells even when cultured without added growth factors, further demonstrating a different myogenic potential of the caudal paraxial mesoderm. Stage 13-14 paraxial mesoderm also exhibited a myogenic response to bFGF/TGF-beta1 but, unlike stage 10-11 embryos, both somites and segmental plate exhibited a strong response. A two-step mechanism for the bFGF/TGF-beta1 effect is suggested by the finding that only TGF-beta1 was required during the first 12 hours of culture, whereas bFGF plus a TGF-beta-like factor were required for the remainder of the culture. The biological relevance of the findings with bFGF is underscored by the observation that a monoclonal antibody to bFGF inhibited myogenic signaling from the dorsal neural tube. However, a monoclonal antibody that can neutralize the three factors TGF-beta1, TGF-beta2 and TGF-beta3 did not block myogenic signals from the neural tube, raising the possibility that another TGF-beta family member may be involved in vivo.
authors.affiliation: University of Washington, Department of Biochemistry, Seattle, 98195, USA.
authors.forename: H M
authors.initials: HM
authors.lastname: Stern
authors.forename: J
authors.initials: J
authors.lastname: Lin-Jones
authors.forename: S D
authors.initials: SD
authors.lastname: Hauschka
mesh_terms: D000818:Animals; D000906:Antibodies; D002490:Central Nervous System / Q000196:embryology* / Q000378:metabolism; D002642:Chick Embryo; D018920:Coculture Techniques; D046508:Culture Techniques; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D016222:Fibroblast Growth Factor 2 / Q000276:immunology / Q000494:pharmacology* / Q000502:physiology; D008648:Mesoderm / Q000166:cytology / Q000187:drug effects; D009132:Muscles / Q000196:embryology*; D018995:Myosin Heavy Chains / Q000032:analysis; D015398:Signal Transduction; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000276:immunology / Q000494:pharmacology* / Q000502:physiology; D015291:Transforming Growth Factors / Q000494:pharmacology
chemical_list: D000906:Antibodies; D016212:Transforming Growth Factor beta; C081351:dorsalin 1 protein, Gallus gallus; D016222:Fibroblast Growth Factor 2; D015291:Transforming Growth Factors; D018995:Myosin Heavy Chains