Signaling via the transcriptionally regulated activin receptor 2B is a novel mediator of neuronal cell death during chicken ciliary ganglion development
Signaling via the transcriptionally regulated activin receptor 2B is a novel mediator of neuronal cell death during chicken ciliary ganglion development
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DOI：
10.1016/j.ijdevneu.2015.01.006
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发表时间：
2015-04-01
影响因子：
1.8
通讯作者：
Krieglstein, K.
中科院分区：
文献类型：
--
作者：
Koszinowski, S.;Buss, K.;Krieglstein, K.
TGF-β配体超家族成员激活素A和BMP控制胚胎神经元发育和分化的重要方面。已知两者均结合激活素受体亚型IIA（ActRIIA）和IIB，而在禽睫状神经节（CG）中，迄今为止仅描述了ActRIIA表达。我们表明，ACVR 2B的表达，编码ActRIIB，在CG发展过程中受到严格的调控，ACVR 2B表达的敲低导致神经元凋亡的执行中的失调，因此影响体内个体发育的程序性细胞死亡。虽然脉络膜神经元的分化在敲低中受阻，指向激活素A介导的神经分化信号传导的减少，但CG中自然发生的神经元细胞死亡并没有被卵泡抑素治疗阻止。另一方面，全身注射BMP拮抗剂noggin减少了凋亡神经元的数量，其程度与ACVR 2B敲低相似。因此，我们提出了一种新的途径，在CG神经元个体发育的程序性细胞死亡的调节，这可能是由BMP和信号通过ActRIIB介导的。(C)2015作者爱思唯尔有限公司出版
The TGF-beta ligand superfamily members activin A and BMP control important aspects of embryonic neuronal development and differentiation. Both are known to bind to activin receptor subtypes IIA (ActRIIA) and IIB, while in the avian ciliary ganglion (CG), so far only ActRIIA-expression has been described. We show that the expression of ACVR2B, coding for the ActRIIB, is tightly regulated during CG development and the knockdown of ACVR2B expression leads to a deregulation in the execution of neuronal apoptosis and therefore affects ontogenetic programmed cell death in vivo. While the differentiation of choroid neurons was impeded in the knockdown, pointing toward a reduction in activin A-mediated neural differentiation signaling, naturally occurring neuronal cell death in the CG was not prevented by follistatin treatment. Systemic injections of the BMP antagonist noggin, on the other hand, reduced the number of apoptotic neurons to a similar extent as ACVR2B knockdown. We therefore propose a novel pathway in the regulation of CG neuron ontogenetic programmed cell death, which could be mediated by BMP and signals via the ActRIIB. (C) 2015 The Authors. Published by Elsevier Ltd.