Marcos-Gutiérrez C V, Wilson S W, Holder N, Pachnis V
Division of Developmental Neurobiology, National Institute for Medical Research, The Ridgeway, London, UK.
Oncogene. 1997 Feb 27;14(8):879-89. doi: 10.1038/sj.onc.1201048.
The c-ret proto-oncogene, a member of the receptor tyrosine kinase gene superfamily, plays a critical role in the development of the excretory system and the enteric and autonomic nervous systems of mammalian embryos. To study the potential function of the c-ret locus in lower vertebrates, we have isolated its zebrafish homologue, ret1 and established its expression pattern during embryogenesis. Ret1 mRNA first appears during early somitogenesis in the presumptive brain, spinal cord and excretory system. Within the CNS, expression of ret1 is detected in primary motor and sensory (Rohon-Beard) neurons. Ret1 transcripts are also expressed in subsets of neural crest cells and cranial ganglia as well as in the enteric nervous system. In the excretory system, expression is detected in the developing nephric duct and the pronephros. Our findings reveal a remarkable similarity in the expression pattern of c-ret between higher and lower vertebrates, suggesting that the function of this locus has been conserved throughout vertebrate evolution. Furthermore, the conservation of ret1 expression in cell types which remain unaffected by the mammalian c-ret mutations, such as motor and sensory neurons, suggests a function of this receptor in these cell lineages.
c-ret原癌基因是受体酪氨酸激酶基因超家族的成员，在哺乳动物胚胎的排泄系统以及肠和自主神经系统的发育中起关键作用。为了研究c-ret基因座在低等脊椎动物中的潜在功能，我们分离了其斑马鱼同源物ret1，并确定了其在胚胎发育过程中的表达模式。Ret1 mRNA最早在体节形成早期出现在推定的脑、脊髓和排泄系统中。在中枢神经系统内，在初级运动和感觉（罗霍恩-比尔）神经元中检测到ret1的表达。Ret1转录本也在神经嵴细胞和颅神经节的亚群以及肠神经系统中表达。在排泄系统中，在发育中的肾管和前肾中检测到表达。我们的发现揭示了高等和低等脊椎动物之间c-ret表达模式的显著相似性，表明该基因座的功能在整个脊椎动物进化过程中得以保留。此外，ret1在不受哺乳动物c-ret突变影响的细胞类型（如运动和感觉神经元）中的表达保守性，表明该受体在这些细胞谱系中具有功能。
