Brorin is required for neurogenesis, gliogenesis, and commissural axon guidance in the zebrafish forebrain

<div><p>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 <i>brorin</i> in order to elucidate its <i>in vivo</i> actions. Zebrafish <i>brorin</i> was predominantly expressed in developing neural tissues. The overexpression of <i>brorin</i> led to the inactivation of Bmp signaling. On the other hand, the knockdown of <i>brorin</i> resulted in the activation of Bmp signaling and <i>brorin</i> morphants exhibited defective development of the ventral domain in the forebrain. Furthermore, the knockdown of <i>brorin</i> inhibited the generation of γ–aminobutyric acid (GABA)ergic interneurons and oligodendrocytes and promoted the generation of astrocytes in the forebrain. In addition, <i>brorin</i> 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.</p></div>