Gutzman Jennifer H, Graeden Ellie, Brachmann Isabel, Yamazoe Sayumi, Chen James K, Sive Hazel
Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Biol Open. 2018 Nov 13;7(11):bio034520. doi: 10.1242/bio.034520.
Basal constriction occurs at the zebrafish midbrain-hindbrain boundary constriction (MHBC) and is likely a widespread morphogenetic mechanism. 3D reconstruction demonstrates that MHBC cells are wedge-shaped, and initially constrict basally, with subsequent apical expansion. is expressed in the MHB and is required for basal constriction. Consistent with a requirement for this pathway, expression of dominant negative Gsk3β overcomes knockdown. Immunostaining identifies focal adhesion kinase (Fak) as active in the MHB region, and knockdown demonstrates Fak is a regulator of basal constriction. Tissue specific knockdown further indicates that Fak functions cell autonomously within the MHBC. Fak acts downstream of , suggesting that Wnt5b signals locally as an early step in basal constriction and acts together with more widespread Fak activation. This study delineates signaling pathways that regulate basal constriction during brain morphogenesis.
基底收缩发生在斑马鱼中脑-后脑边界收缩处(MHBC),并且可能是一种广泛存在的形态发生机制。三维重建显示,MHBC细胞呈楔形,最初从基底开始收缩,随后顶端扩张。[具体基因名称]在中脑-后脑边界(MHB)表达,是基底收缩所必需的。与该信号通路的需求一致,显性负性Gsk3β的表达克服了[具体基因名称]的敲低。免疫染色确定粘着斑激酶(Fak)在MHB区域有活性,敲低实验表明Fak是基底收缩的调节因子。组织特异性敲低进一步表明Fak在MHBC内自主发挥作用。Fak在[具体基因名称]下游起作用,这表明Wnt5b作为基底收缩的早期步骤在局部发出信号,并与更广泛的Fak激活共同发挥作用。这项研究描绘了在脑形态发生过程中调节基底收缩的信号通路。