Brorin is required for neurogenesis, gliogenesis, and commissural axon guidance in the zebrafish forebrain.
Brorin is required for neurogenesis, gliogenesis, and commissural axon guidance in the zebrafish forebrain.
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DOI：
10.1371/journal.pone.0176036
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Itoh N
中科院分区：
文献类型：
--
作者：
Miyake A;Mekata Y;Fujibayashi H;Nakanishi K;Konishi M;Itoh N
bmp通过它们的调节器调节许多神经功能。我们之前在人类、小鼠和斑马鱼中发现了一种Bmp信号的神经特异性分泌拮抗剂broin。小鼠Brorin有两个富含半胱氨酸的结构域，在其核心区域含有10个半胱氨酸残基，它们位于与Chordin家族成员的富含半胱氨酸结构域相似的位置，Chordin家族成员是分泌Bmp拮抗剂。斑马鱼的broin有两个富含半胱氨酸的结构域，与小鼠的broin结构域具有较高的相似性。我们在此检查斑马鱼的broin，以阐明其在体内的作用。斑马鱼主要在发育中的神经组织中表达broin。broin的过表达导致Bmp信号的失活。另一方面，敲低broin导致Bmp信号的激活，并且broin变形体表现出前脑腹侧区域发育缺陷。此外，敲低broin可抑制γ -氨基丁酸（GABA）能间神经元和少突胶质细胞的生成，促进前脑星形胶质细胞的生成。此外，前脑的轴突引导也需要溴化蛋白。目前的研究结果表明，broin是一种分泌的Bmp拮抗剂，主要在发育中的神经组织中表达，并在斑马鱼前脑的发育中发挥多种作用。
Bmps regulate numerous neural functions with their regulators. We previously identified Brorin, a neural-specific secreted antagonist of Bmp signaling, in humans, mice, and zebrafish. Mouse Brorin has two cysteine-rich domains containing 10 cysteine residues in its core region, and these are located in similar positions to those in the cysteine-rich domains of Chordin family members, which are secreted Bmp antagonists. Zebrafish Brorin had two cysteine-rich domains with high similarity to those of mouse Brorin. We herein examined zebrafish brorin in order to elucidate its in vivo actions. Zebrafish brorin was predominantly expressed in developing neural tissues. The overexpression of brorin led to the inactivation of Bmp signaling. On the other hand, the knockdown of brorin resulted in the activation of Bmp signaling and brorin morphants exhibited defective development of the ventral domain in the forebrain. Furthermore, the knockdown of brorin inhibited the generation of γ–aminobutyric acid (GABA)ergic interneurons and oligodendrocytes and promoted the generation of astrocytes in the forebrain. In addition, brorin was required for axon guidance in the forebrain. The present results suggest that Brorin is a secreted Bmp antagonist predominantly expressed in developing neural tissues and that it plays multiple roles in the development of the zebrafish forebrain.