Govindarajan V, Ramachandran R K, George J M, Shakes D C, Tomlinson C R
Department of Biology, University of Houston, Texas 77204-5513, USA.
Dev Biol. 1995 Dec;172(2):541-51. doi: 10.1006/dbio.1995.8059.
Growth factors and the extracellular matrix have been shown to fulfill vital developmental roles in many embryonic systems. Our hypothesis is that a developmental role played by the extracellular matrix in sea urchins may be the binding of a PDGF-like growth factor to promote signaling activity. We report here that anti-human PDGF-B antibodies and anti-human TGF-alpha antibodies immunoprecipitated specific proteins isolated from Lytechinus embryos. Addition of these antibodies to Lytechinus embryos inhibited gastrulation and spiculogenesis. The embryos are sensitive to the antibodies from the four-cell through the hatching blastula stages, which suggests that the TGF-alpha-like and PDGF-like ligands are required for the early differentiation of the gut and spicules. We present evidence that the PDGF-like growth factor depends on the extracellular matrix for signaling activity. Synthetic peptides representing the heparan sulfate proteoglycan binding sequence on human PDGF-B were added to Lytechinus embryo cultures to compete for binding sites with the endogenous PDGF-like growth factor. The experimental peptide inhibited gastrulation and caused radially arranged multiple spicules to form. Development was unaffected by a control peptide. These studies support our hypothesis and suggest that TGF-alpha-like and PDGF-like growth factors induce signaling events required for sea urchin gastrulation and spiculogenesis and suggest that an extracellular matrix-associated PDGF-like growth factor is involved in differentiation along the oral-aboral axis.
生长因子和细胞外基质已被证明在许多胚胎系统中发挥着至关重要的发育作用。我们的假设是,细胞外基质在海胆中所起的发育作用可能是通过结合一种血小板衍生生长因子(PDGF)样生长因子来促进信号传导活性。我们在此报告,抗人PDGF - B抗体和抗人转化生长因子α(TGF - α)抗体免疫沉淀了从长海胆胚胎中分离出的特定蛋白质。将这些抗体添加到长海胆胚胎中会抑制原肠胚形成和骨针形成。从四细胞期到孵化囊胚期,胚胎对这些抗体都很敏感,这表明TGF - α样和PDGF样配体是肠道和骨针早期分化所必需的。我们提供的证据表明,PDGF样生长因子的信号传导活性依赖于细胞外基质。将代表人类PDGF - B上硫酸乙酰肝素蛋白聚糖结合序列的合成肽添加到长海胆胚胎培养物中,以与内源性PDGF样生长因子竞争结合位点。实验肽抑制了原肠胚形成,并导致径向排列的多个骨针形成。对照肽对发育没有影响。这些研究支持了我们的假设,并表明TGF - α样和PDGF样生长因子诱导海胆原肠胚形成和骨针形成所需的信号事件,并表明一种与细胞外基质相关的PDGF样生长因子参与了沿口 - 反口轴的分化。