Sahu Srishti U, Visetsouk Mike R, Garde Ryan J, Hennes Leah, Kwas Constance, Gutzman Jennifer H
Department of Biological Sciences, University of Wisconsin-Milwaukee, Milwaukee, WI 53201.
Department of Biological Sciences, University of Wisconsin-Milwaukee, Milwaukee, WI 53201
Mol Biol Cell. 2017 Apr 1;28(7):875-882. doi: 10.1091/mbc.E16-08-0561. Epub 2017 Feb 1.
One of the first morphogenetic events in the vertebrate brain is the formation of the highly conserved midbrain-hindbrain boundary (MHB). Specific cell shape changes occur at the point of deepest constriction of the MHB, the midbrain-hindbrain boundary constriction (MHBC), and are critical for proper MHB formation. These cell shape changes are controlled by nonmuscle myosin II (NMII) motor proteins, which are tightly regulated via the phosphorylation of their associated myosin regulatory light chains (MRLCs). However, the upstream signaling pathways that initiate the regulation of NMII to mediate cell shape changes during MHB morphogenesis are not known. We show that intracellular calcium signals are critical for the regulation of cell shortening during initial MHB formation. We demonstrate that the MHB region is poised to respond to calcium transients that occur in the MHB at the onset of MHB morphogenesis and that calcium mediates phosphorylation of MRLC specifically in MHB tissue. Our results indicate that (), expressed specifically in the MHB, and myosin light chain kinase together mediate MHBC cell length. Our data suggest that modulation of NMII activity by calcium is critical for proper regulation of cell length to determine embryonic brain shape during development.
脊椎动物大脑中最早的形态发生事件之一是高度保守的中脑-后脑边界（MHB）的形成。在MHB最深收缩点，即中脑-后脑边界收缩（MHBC）处会发生特定的细胞形态变化，这些变化对于MHB的正常形成至关重要。这些细胞形态变化由非肌肉肌球蛋白II（NMII）运动蛋白控制，该蛋白通过其相关的肌球蛋白调节轻链（MRLC）的磷酸化进行严格调控。然而，在MHB形态发生过程中启动对NMII的调节以介导细胞形态变化的上游信号通路尚不清楚。我们发现细胞内钙信号对于初始MHB形成过程中细胞缩短的调节至关重要。我们证明MHB区域准备好对MHB形态发生开始时在MHB发生的钙瞬变做出反应，并且钙特异性地介导MHB组织中MRLC的磷酸化。我们的结果表明，在MHB中特异性表达的（）与肌球蛋白轻链激酶共同介导MHBC细胞长度。我们的数据表明，钙对NMII活性的调节对于在发育过程中正确调节细胞长度以确定胚胎脑形态至关重要。
