Widelitz R B, Jiang T X, Noveen A, Chen C W, Chuong C M
Department of Pathology, University of Southern California, Los Angeles 90033, USA.
J Invest Dermatol. 1996 Dec;107(6):797-803. doi: 10.1111/1523-1747.ep12330553.
Induction of skin appendages involves a cascade of molecular events. The fibroblast growth factor (FGF) family of peptide growth factors is involved in cell proliferation and morphogenesis. We explored the role of the FGFs during skin appendage induction using developing chicken feather buds as a model. FGF-1, FGF-2, or FGF-4 was added directly to the culture medium or was released from pre-soaked Affigel blue beads. Near the midline, FGFs led to fusion of developing feather buds, representing FGFs' ability to expand feather bud domains in developing skin. In lateral regions of the explant where feather placodes have not formed, FGF treatment produces a zone of condensation and a region with an increased number of feather buds. In ventral epidermis that is normally apteric (without feathers), FGFs can also induce new feather buds. Like normal feather buds, the newly induced buds express Shh. The expression of Grb, Ras, Raf, and Erk, intracellular signaling molecules known to be downstream to tyrosine kinase receptors such as the FGF receptor, was enriched in feather bud domains. Genistein, an inhibitor of tyrosine kinase, suppressed feather bud formation and the effect of FGF. These results indicate that there are varied responses to FGFs depending on epithelial competence. All the phenotypic responses, however, show that FGFs facilitate the formation of skin appendage domains.
皮肤附属器的诱导涉及一系列分子事件。肽生长因子的成纤维细胞生长因子(FGF)家族参与细胞增殖和形态发生。我们以发育中的鸡羽毛芽为模型,探索了FGFs在皮肤附属器诱导过程中的作用。FGF-1、FGF-2或FGF-4被直接添加到培养基中,或从预先浸泡的Affigel蓝珠中释放出来。在中线附近,FGFs导致发育中的羽毛芽融合,这代表了FGFs在发育中的皮肤中扩展羽毛芽区域的能力。在植块的外侧区域,即尚未形成羽毛基板的地方,FGF处理会产生一个凝聚区和一个羽毛芽数量增加的区域。在通常无羽(无毛)的腹侧表皮中,FGFs也能诱导新的羽毛芽。与正常羽毛芽一样,新诱导的芽表达Shh。Grb、Ras、Raf和Erk这些已知为酪氨酸激酶受体(如FGF受体)下游的细胞内信号分子的表达,在羽毛芽区域富集。酪氨酸激酶抑制剂染料木黄酮抑制了羽毛芽的形成以及FGF的作用。这些结果表明,根据上皮细胞的反应能力,对FGFs存在不同的反应。然而,所有的表型反应都表明,FGFs促进了皮肤附属器区域的形成。