Lee King-Yiu, Samy Eileen Teresa, Sham Mai-Har, Tam Paul Kwong-Hang, Lui Vincent Chi-Hang
Department of Surgery, the University of Hong Kong, Pokfulam Road, Pokfulam, SAR, Hong Kong, China.
Biochim Biophys Acta. 2003 May 13;1627(1):26-38. doi: 10.1016/s0167-4781(03)00068-x.
The RET protooncogene encodes for a transmembrane receptor tyrosine kinase and plays a crucial role in nephrogenesis and the enteric nervous system (ENS) development. Alternative splicing at the 3' end of the RET gene generates 3' splicing variants that encode RET 9, RET 51 and RET 43 isoforms. It has been hypothesized that these isoforms perform distinct functions and that their expressions are differentially regulated during mammalian development. To gain an insight into the expression patterns of various ret isoforms during embryogenesis, we investigate the temporal and spatial expressions of ret gene in mouse embryos and in adult mice. We characterized the 3' end of the mouse ret gene and localized the alternatively spliced exons. Using 3' rapid amplification of cDNA ends (3' RACE) and reverse transcription-polymerase chain reaction (RT-PCR), ret 9 and ret 51 transcripts were identified in both mouse embryos and adult mouse tissues. However, the ret 43 transcript was not. Using in situ hybridization, we showed that ret 9 was the dominant ret encoding transcript in mouse embryos. Transcripts of ret 9 were detected in all cranial ganglia; in the sensory and autonomic ganglia of the trunk; in a subset of neurons of the dorsal root ganglion (DRG); in the motor neurons of the spinal cord; in the developing lung and excretory systems; in the enteric neuroblasts of the ENS; and in the thyroid lobes. In contrast, ret 51 expression was weak and restricted to the motor column of the spinal cord, the DRG, the enteric neuroblasts, the lung bud and the kidney. In adult mice, ret 9 expression was relatively widespread in many organs while that of ret 51 was rather restricted. Our data indicated that ret isoforms are temporally and spatially regulated in mouse embryos and adult mouse.
RET原癌基因编码一种跨膜受体酪氨酸激酶，在肾发生和肠神经系统（ENS）发育中起关键作用。RET基因3'端的可变剪接产生3'剪接变体，其编码RET 9、RET 51和RET 43异构体。据推测，这些异构体具有不同的功能，并且它们的表达在哺乳动物发育过程中受到差异调节。为了深入了解胚胎发育过程中各种ret异构体的表达模式，我们研究了ret基因在小鼠胚胎和成年小鼠中的时空表达。我们对小鼠ret基因的3'端进行了表征，并定位了可变剪接外显子。使用3' cDNA末端快速扩增（3' RACE）和逆转录-聚合酶链反应（RT-PCR），在小鼠胚胎和成年小鼠组织中均鉴定出ret 9和ret 51转录本。然而，未检测到ret 43转录本。通过原位杂交，我们发现ret 9是小鼠胚胎中主要的ret编码转录本。在所有颅神经节中均检测到ret 九转录本；在躯干的感觉和自主神经节中；在背根神经节（DRG）的一部分神经元中；在脊髓的运动神经元中；在发育中的肺和排泄系统中；在ENS的肠神经母细胞中；以及在甲状腺叶中。相比之下，ret 51的表达较弱，仅限于脊髓的运动柱、DRG、肠神经母细胞、肺芽和肾脏。在成年小鼠中，ret 9的表达在许多器官中相对广泛，而ret 51的表达则相当局限。我们的数据表明，ret异构体在小鼠胚胎和成年小鼠中受到时空调节。
