确定初级纤毛控制中脑多巴胺能神经发生的关键时空窗口。
Definition of a critical spatiotemporal window within which primary cilia control midbrain dopaminergic neurogenesis.
作者信息
Gazea Mary, Tasouri Evangelia, Heigl Tobias, Bosch Viktoria, Tucker Kerry L, Blaess Sandra
机构信息
Institute of Reconstructive Neurobiology, University of Bonn , Bonn, Germany.
Interdisciplinary Center for Neurosciences, University of Heidelberg, Heidelberg, Germany; Institute of Anatomy and Cell Biology, University of Heidelberg, Heidelberg, Germany.
出版信息
Neurogenesis (Austin). 2016 Oct 20;3(1):e1248206. doi: 10.1080/23262133.2016.1248206. eCollection 2016.
Midbrain dopaminergic (mDA) neurons are generated in the ventral midbrain floor plate depending on Sonic Hedgehog (SHH) signaling for induction. Primary cilia transduce canonical SHH signals. Loss of intraflagellar transport protein IFT88, essential for ciliary function, disrupts SHH signaling in the ventral midbrain and results in the reduction in mDA progenitors and neurons. We investigate whether conditional inactivation of the kinesin motor protein KIF3A recapitulates phenotypes observed in conditional mutants. Conditional inactivation reduced the mDA progenitor domain size, but did not result in mDA neuron reduction most likely because of a delayed loss of cilia and delayed inactivation of SHH signaling. We thereby define a precise spatiotemporal window within which primary cilia-dependent SHH signaling determines mDA fate.
中脑多巴胺能（mDA）神经元在腹侧中脑底板生成，其诱导依赖于音猬因子（SHH）信号。初级纤毛转导典型的SHH信号。对于纤毛功能至关重要的鞭毛内运输蛋白IFT88的缺失，会破坏腹侧中脑的SHH信号，并导致mDA祖细胞和神经元数量减少。我们研究了驱动蛋白运动蛋白KIF3A的条件性失活是否会重现条件性突变体中观察到的表型。条件性失活减小了mDA祖细胞结构域的大小，但最有可能由于纤毛的延迟丧失和SHH信号的延迟失活，并未导致mDA神经元数量减少。由此，我们确定了一个精确的时空窗口，在此窗口内，依赖初级纤毛的SHH信号决定mDA命运。
Zotero 插件