Renal agenesis and hypodysplasia in ret-k- mutant mice result from defects in ureteric bud development.
Renal agenesis and hypodysplasia in ret-k- mutant mice result from defects in ureteric bud development.
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发表时间：
1996-06
期刊：
影响因子：
4.6
通讯作者：
A. Schuchardt;V. D’Agati;V. Pachnis;F. Costantini
中科院分区：
文献类型：
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作者：
A. Schuchardt;V. D’Agati;V. Pachnis;F. Costantini
c-ret基因编码一种受体酪氨酸激酶，在发育中的排泄系统的沃尔夫管和输尿管芽中表达。新生小鼠c-ret突变纯合子显示肾发育不全或严重发育不全，这表明该基因在后肾发育中的关键作用。为了研究这些缺陷的胚胎学基础，我们表征了突变纯合子排泄系统的早期发育，并观察到输尿管芽形成、生长和分支的一系列缺陷，这些缺陷解释了出生时所见的肾缺陷谱。离体输尿管芽和后肾间充质的共培养表明，原发性缺陷是输尿管芽固有的。虽然突变芽未能响应野生型间充质的诱导，突变间充质有能力诱导野生型芽的生长和分支。此外，当与胚胎脊髓共培养时，突变后肾间充质显示出正常的分化为肾小管的能力。这些研究结果表明，c-ret编码受体的模型（尚未确定）的后肾间充质，介导该组织的诱导作用后，输尿管芽产生的因素。该因子似乎刺激输尿管芽从沃尔夫管的初始外翻，以及其随后的生长和分支。
The c-ret gene encodes a receptor tyrosine kinase that is expressed in the Wolffian duct and ureteric bud of the developing excretory system. Newborn mice homozygous for a mutation in c-ret displayed renal agenesis or severe hypodysplasia, suggesting a critical role for this gene in metanephric kidney development. To investigate the embryological basis of these defects, we characterized the early development of the excretory system in mutant homozygotes, and observed a range of defects in the formation, growth and branching of the ureteric bud, which account for the spectrum of renal defects seen at birth. Co-culture of isolated ureteric buds and metanephric mesenchyme show that the primary defect is intrinsic to the ureteric bud. While the mutant bud failed to respond to induction by wild-type mesenchyme, mutant mesenchyme was competent to induce the growth and branching of the wild-type bud. Furthermore, the mutant metanephric mesenchyme displayed a normal capacity to differentiate into nephric tubules when co-cultured with embryonic spinal cord. These findings suggest a model in which c-ret encodes the receptor for a (yet to be identified) factor produced by the metanephric mesenchyme, which mediates the inductive effects of this tissue upon the ureteric bud. This factor appears to stimulate the initial evagination of the ureteric bud from the Wolffian duct, as well as its subsequent growth and branching.