Ivanchuk S M, Eng C, Cavenee W K, Mulligan L M
Department of Pathology, Queen's University, Kingston, ON, Canada.
Oncogene. 1997 Apr 17;14(15):1811-8. doi: 10.1038/sj.onc.1201016.
A series of inductive events between two different cell groups, the ureteric bud epithelium and metanephric mesenchyme, gives rise to the functional mammalian kidney. These reciprocal inductive interactions involve a number of molecules, one of which is the RET receptor tyrosine kinase. The phenotype of mice lacking functional RET includes kidney agenesis or severe dysgenesis, indicating a requirement for RET in kidney organogenesis. To investigate RET expression in human kidney development, we used a semi-quantitative RT-PCR-based strategy to examine a panel of kidney RNA samples ranging from 8-24 weeks gestational age. We found RET expression was highest earlier in development (14 weeks) with expression decreasing through to 24 weeks gestation. While three alternative RET transcripts generated by exon skipping at the 5' end of the gene were all detected throughout kidney development, expression of one transcript, RET2/6, where exon 2 was spliced to exon 6, varied relative to full length RET during this period. Levels of RET2/6 were highest at the earliest age of fetal kidney examined (8 weeks) and decreased relative to all other RET transcripts to low adult levels. The period of high expression coincides with a period of rapid bud bifurcation. Thus, it is possible that RET2/6 has a role in the early growth and differentiation of the human kidney.
在两个不同的细胞群，即输尿管芽上皮和后肾间充质之间发生的一系列诱导事件，导致了功能性哺乳动物肾脏的形成。这些相互的诱导性相互作用涉及多种分子，其中之一是RET受体酪氨酸激酶。缺乏功能性RET的小鼠的表型包括肾缺如或严重发育异常，这表明肾脏器官发生过程中需要RET。为了研究RET在人类肾脏发育中的表达情况，我们采用了基于半定量逆转录聚合酶链反应（RT-PCR）的策略，检测了一组孕龄在8至24周之间的肾脏RNA样本。我们发现RET的表达在发育早期（14周）最高，随后在整个孕期逐渐下降，直至24周。虽然在整个肾脏发育过程中都检测到了由该基因5'端外显子跳跃产生的三种RET可变转录本，但其中一种转录本RET2/6（外显子2剪接到外显子6）的表达在此期间相对于全长RET有所变化。RET2/6的水平在检测的最早胎肾年龄（8周）时最高，相对于所有其他RET转录本而言，其水平下降至成人的低水平。高表达期与快速的芽分支期相吻合。因此，RET2/6有可能在人类肾脏的早期生长和分化中发挥作用。
