Haigo Saori L, Hildebrand Jeffrey D, Harland Richard M, Wallingford John B
Department of Molecular and Cell Biology, 16 Barker Hall, University of California-Berkeley, Berkeley, CA 94720, USA.
Curr Biol. 2003 Dec 16;13(24):2125-37. doi: 10.1016/j.cub.2003.11.054.
The morphogenetic events of early vertebrate development generally involve the combined actions of several populations of cells, each engaged in a distinct behavior. Neural tube closure, for instance, involves apicobasal cell heightening, apical constriction at hingepoints, convergent extension of the midline, and pushing by the epidermis. Although a large number of genes are known to be required for neural tube closure, in only a very few cases has the affected cell behavior been identified. For example, neural tube closure requires the actin binding protein Shroom, but the cellular basis of Shroom function and how it influences neural tube closure remain to be elucidated.
We show here that expression of Shroom is sufficient to organize apical constriction in transcriptionally quiescent, naive epithelial cells but not in non-polarized cells. Shroom-induced apical constriction was associated with enrichment of apically localized actin filaments and required the small GTPase Rap1 but not Rho. Endogenous Xenopus shroom was found to be expressed in cells engaged in apical constriction. Consistent with a role for Shroom in organizing apical constriction, disrupting Shroom function resulted in a specific failure of hingepoint formation, defective neuroepithelial sheet-bending, and failure of neural tube closure.
These data demonstrate that Shroom is an essential regulator of apical constriction during neurulation. The finding that a single protein can initiate this process in epithelial cells establishes that bending of epithelial sheets may be patterned during development by the regulation of expression of single genes.
早期脊椎动物发育的形态发生事件通常涉及多个细胞群体的联合作用，每个群体都参与一种独特的行为。例如，神经管闭合涉及细胞顶基高度增加、铰链点处的顶端收缩、中线的汇聚延伸以及表皮的推动。尽管已知大量基因是神经管闭合所必需的，但只有极少数情况下受影响的细胞行为得到了明确。例如，神经管闭合需要肌动蛋白结合蛋白Shroom，但Shroom功能的细胞基础及其如何影响神经管闭合仍有待阐明。
我们在此表明，Shroom的表达足以在转录静止的原始上皮细胞中组织顶端收缩，但在非极化细胞中则不然。Shroom诱导的顶端收缩与顶端定位的肌动蛋白丝的富集相关，并且需要小GTP酶Rap1而不是Rho。发现内源性非洲爪蟾Shroom在参与顶端收缩的细胞中表达。与Shroom在组织顶端收缩中的作用一致，破坏Shroom功能导致铰链点形成的特定失败、神经上皮片弯曲缺陷以及神经管闭合失败。
这些数据表明，Shroom是神经胚形成过程中顶端收缩的重要调节因子。单一蛋白质能够在上皮细胞中启动这一过程的发现表明，上皮片的弯曲可能在发育过程中通过单一基因表达的调控而形成模式。
