c-ret regulates cholinergic properties in mouse sympathetic neurons: evidence from mutant mice
c-ret regulates cholinergic properties in mouse sympathetic neurons: evidence from mutant mice
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DOI：
10.1111/j.1460-9568.2004.03500.x
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发表时间：
2004-07-01
影响因子：
3.4
通讯作者：
Ernsberger, U
中科院分区：
文献类型：
--
作者：
Burau, K;Stenull, I;Ernsberger, U
寻找调节去甲肾上腺素能和胆碱能交感神经元发育的信号系统是发育神经科学的经典问题。虽然骨形态发生蛋白诱导去甲肾上腺素能特性的重要作用是牢固确立的，但体内胆碱能特性的发展所涉及的因素仍然是谜。先前的研究表明，c-ret受体和胆碱能特性在鸡交感神经元中共表达。使用原位杂交，我们现在表明，小鼠c-ret受体的功能丧失突变显着减少了细胞的数量呈阳性的胆碱乙酰转移酶（ChAT）和囊泡乙酰胆碱转运蛋白（VAChT）在星状神经节的纯合子新生动物。酪氨酸羟化酶（TH）mRNA，去甲肾上腺素合成的限速酶，阳性神经元的数量减少到一个较小的程度，表达水平没有可检测的改变。在胚胎第16天（E16），ChAT和VAChT阳性细胞已经受到c-ret突变的影响。然而，在E14，ChAT和VAChT mRNA在低水平下可检测到，并且在野生型和突变小鼠之间没有观察到差异。我们的数据表明，c-ret信号是必要的胆碱能交感神经元的成熟，但从头诱导ChAT和VAChT的表达。
The search for signalling systems regulating development of noradrenergic and cholinergic sympathetic neurons is a classical problem of developmental neuroscience. While an essential role of bone morphogenetic proteins for induction of noradrenergic properties is firmly established, factors involved in the development of cholinergic traits in vivo are still enigmatic. Previous studies have shown that the c-ret receptor and cholinergic properties are coexpressed in chick sympathetic neurons. Using in situ hybridization we show now that a loss-of-function mutation of the c-ret receptor in mice dramatically reduces numbers of cells positive for choline acetyltransferase (ChAT) and the vesicular acetylcholine transporter (VAChT) in stellate ganglia of homozygous newborn animals. The number of neurons positive for tyrosine hydroxylase (TH) mRNA, the rate-limiting enzyme of noradrenaline synthesis, is reduced to a smaller degree and expression levels are not detectably altered. Already at embryonic day 16 (El 6), ChAT and VAChT-positive cells are affected by the c-ret mutation. At E14, however, ChAT and VAChT mRNAs are detectable at low levels and no difference is observed between wildtype and mutant mice. Our data suggest that c-ret signalling is necessary for the maturation of cholinergic sympathetic neurons but dispensable for de novo induction of ChAT and VAChT expression.