期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2013
卷号：110
期号：42
页码：16892-16897
DOI：10.1073/pnas.1306282110
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：The posterior lateral line primordium in zebrafish provides an amenable model to study mechanisms of collective cell migration. The directed migration of the cell cluster along the path of Sdf1a chemokine requires two receptors, Cxcr4b and Cxcr7b, which are expressed in the leading and trailing part of the primordium, respectively. The polarized expression of receptors is regulated by Wnt signaling, but downstream players mediating this control remain to be found. Here, we show that the Hox homeobox gene Hoxb8a is a critical component that acts downstream of the Wnt pathway to coordinate the expression of both chemokine receptors. We find that Hoxb8a is expressed in the leading part of the primordium and is required for the correct speed and extent of migration. Hoxb8a expression is dependent upon Wnt activity and needed both for cxcr4b expression and to repress and thus restrict cxcr7b expression to the trailing zone of the primordium. In the absence of Wnt activity, overexpressed Hoxb8a is able to repress cxcr7b but not up-regulate cxcr4b expression. Together with results from expressing dominant activator and repressor constructs, these findings suggest that Hoxb8a is induced by and cooperates with Wnt signaling to up-regulate cxcr4b, and acts through multiple mechanisms to repress cxcr7b expression.
