Expression of the c-ret proto-oncogene during mouse embryogenesis.
Expression of the c-ret proto-oncogene during mouse embryogenesis.
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DOI：
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发表时间：
1993-12
期刊：
影响因子：
4.6
通讯作者：
V. Pachnis;B. Mankoo;F. Costantini
中科院分区：
文献类型：
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作者：
V. Pachnis;B. Mankoo;F. Costantini
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，并利用Northern杂交、组织切片原位杂交和整体杂交组织化学方法分析了小鼠胚胎发育过程中的表达模式。C-ret转录本在胚胎发育第8.5天开始被检测到，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系中观察到。在第8.5-9.5天的颅区，c-ret mRNA仅限于一群从菱形4迁移而来的形成面听神经节原基的神经脊细胞，以及与面听神经节的表面外胚层和咽内胚层密切相关的区域。发育后期(10.5~14.5天)，c-ret基因在所有脑神经节均有表达。在躯干周围神经系统，c-ret在自主神经节和背根神经节的细胞亚群中有表达。在肠道神经系统中，c-ret主要表达于迷走神经脊部的肠神经母细胞(9.0-11.5天)和肠道的肌间神经节(13.5-14.5天)。在中枢神经系统的几个区域，包括腹神经管的未分化神经上皮细胞(8.5天)、脊髓和后脑的运动神经元(10.5-14.5天)、胚胎神经视网膜(13.5天)以及出生后视网膜的神经节、无长突细胞和水平细胞的各层均可观察到c-ret基因的表达。在神经系统外，c-ret在8.5-10.5天的肾(Wolffian)管、11.0-11.5天的输尿管芽上皮(而不是周围的后肾间充质)和13.5-17.5天的肾集合管的生长端(但不包括先前形成的集合管的皮质下部分或间充质来源的小泡)有表达。我们的结果表明，c-ret基因可能编码一种因子的受体，该因子参与了多种神经细胞系的增殖、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。
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.