Helms J A, Kim C H, Hu D, Minkoff R, Thaller C, Eichele G
Department of Orthopaedic Surgery, University of California at San Francisco, 94143, USA.
Dev Biol. 1997 Jul 1;187(1):25-35. doi: 10.1006/dbio.1997.8589.
The face is one of the most intricately patterned structures in human and yet little is known of the mechanisms by which the tissues are instructed to grow, fuse, and differentiate. We undertook a study to determine if the craniofacial primordia used the same molecular cues that mediate growth and patterning in other embryonic tissues such as the neural tube and the limb. Here we provide evidence for the presence of organizer-like tissues in the craniofacial primordia. These candidate organizers express the polarizing signal sonic hedghog (shh) and its putative receptor, patched, as well as fibroblast growth factor 8 and bone morphogeneic protein 2. Shh-expressing epithelial grafts functioned as organizing tissues in a limb bud assay system, where they evoked duplications of the digit pattern. High doses of retinoic acid, which are known to truncate the growth of the frontonasal and maxillary processes and thus produce bilateral clefting of the lip and palate, inhibited the expression of shh and patched but not fgf8, in the craniofacial primordia, and abolished polarizing activity of these tissues. From these studies we conclude that the embryonic face contains signaling centers in the epithelium that participate in craniofacial growth and patterning. In addition, we discuss a novel mechanism whereby retinoids can exert a teratogenic effect on craniofacial morphogenesis independent of its effects on Hox gene expression or neural crest cell migration.
面部是人体中结构模式最为复杂的部位之一，但对于指导组织生长、融合和分化的机制却知之甚少。我们开展了一项研究，以确定颅面原基是否利用了与介导其他胚胎组织（如神经管和四肢）生长及模式形成相同的分子信号。在此，我们提供证据表明颅面原基中存在类似组织者的组织。这些候选组织者表达极化信号音猬因子（shh）及其假定受体patched，以及成纤维细胞生长因子8和骨形态发生蛋白2。在肢芽检测系统中，表达Shh的上皮移植物发挥组织作用，引发指（趾）模式重复。高剂量视黄酸已知会截断额鼻突和上颌突的生长，从而导致唇腭裂，它抑制了颅面原基中shh和patched的表达，但不影响fgf8的表达，并消除了这些组织的极化活性。从这些研究中我们得出结论，胚胎面部上皮中含有参与颅面生长和模式形成的信号中心。此外，我们还讨论了一种新机制，即类维生素A可对颅面形态发生产生致畸作用，而与它对Hox基因表达或神经嵴细胞迁移的影响无关。
