Pachnis V, Mankoo B, Costantini F
Department of Genetics and Development, Columbia University, New York, NY 10032.
Development. 1993 Dec;119(4):1005-17. doi: 10.1242/dev.119.4.1005.
The c-ret proto-oncogene encodes a receptor tyrosine kinase whose normal function has yet to be determined. To begin to investigate the potential role of this gene in vertebrate development, we have isolated cDNA clones representing the murine c-ret gene, and have analyzed the pattern of expression during mouse embryogenesis, using northern blotting, in situ hybridization to histological sections and whole-mount hybridization histochemistry. c-ret transcripts were detected beginning at day 8.5 of embryogenesis, and were observed in a number of cell lineages in the developing peripheral and central nervous systems, as well as in the excretory system. In the cranial region at day 8.5-9.5, c-ret mRNA was restricted to a population of neural crest cells migrating from rhombomere 4 and forming the anlage of the facioacoustic ganglion, as well as to a closely associated domain of surface ectoderm and pharyngeal endoderm. At later stages (10.5-14.5 days), c-ret mRNA was observed in all cranial ganglia. In the peripheral nervous system of the trunk, c-ret was expressed in the autonomic ganglia and in subsets of cells in the dorsal root ganglia. In the enteric nervous system, c-ret was expressed in the presumptive enteric neuroblasts of the vagal crest (day 9.0-11.5), and in the myenteric ganglia of the gut (day 13.5-14.5). c-ret mRNA was observed in several regions of the central nervous system, including the undifferentiated neuroepithelial cells of the ventral neural tube (8.5 days), the motor neurons in the spinal cord and the hindbrain (10.5-14.5 days), the embryonic neuroretina (day 13.5) and the layers of the postnatal retina containing ganglion, amacrine and horizontal cells. Outside the nervous system, c-ret was expressed in the nephric (Wolffian) duct at day 8.5-10.5, the ureteric bud epithelium (but not the surrounding metanephric mesenchyme) at day 11.0-11.5, and the growing tips of the renal collecting ducts (but not the previously formed, subcortical portions of the collecting ducts, or the mesenchyme-derived renal vesicles) at day 13.5-17.5. Our results suggest that the c-ret gene may encode the receptor for a factor involved in the proliferation, migration, differentiation or survival of a variety of neuronal cell lineages, as well as in inductive interactions during organogenesis of the kidney.
原癌基因c-ret编码一种受体酪氨酸激酶，其正常功能尚未确定。为了开始研究该基因在脊椎动物发育中的潜在作用，我们分离了代表小鼠c-ret基因的cDNA克隆，并使用Northern印迹、组织切片原位杂交和全胚胎杂交组织化学分析了小鼠胚胎发育过程中的表达模式。在胚胎发育第8.5天开始检测到c-ret转录本，并在发育中的外周和中枢神经系统以及排泄系统的许多细胞谱系中观察到。在第8.5 - 9.5天的颅区，c-ret mRNA局限于从菱脑节4迁移并形成面听神经节原基的一群神经嵴细胞，以及与之紧密相连的表面外胚层和咽内胚层区域。在后期阶段（10.5 - 14.5天），在所有颅神经节中都观察到c-ret mRNA。在躯干的外周神经系统中，c-ret在自主神经节和背根神经节的部分细胞中表达。在肠神经系统中，c-ret在迷走神经嵴的假定肠神经母细胞（第9.0 - 11.5天）和肠道的肌间神经节（第13.5 - 14.5天）中表达。在中枢神经系统的几个区域观察到c-ret mRNA，包括腹侧神经管的未分化神经上皮细胞（第8.5天）、脊髓和后脑的运动神经元（第10.5 - 14.5天）、胚胎神经视网膜（第13.5天）以及出生后视网膜中含有神经节、无长突和水平细胞的层。在神经系统之外，c-ret在第8.5 - 10.5天的中肾（沃尔夫管）、第11.0 - 11.5天的输尿管芽上皮（但不包括周围的后肾间充质）以及第13.5 - 17.5天的肾集合管生长尖端（但不包括先前形成的皮质下集合管部分或间充质来源的肾小泡）中表达。我们的结果表明，c-ret基因可能编码一种因子的受体，该因子参与多种神经元细胞谱系的增殖迁移、分化或存活，以及肾脏器官发生过程中的诱导相互作用。
