Defective Nodal and Cerl2 expression in the Arl13b^hnn mutant node underlie its heterotaxia

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• 作者：Christine E. Larkins^a ; ^b ; Alyssa Bushey Long^a ; Tamara Caspary^a ; ^{tcaspar@emory.edu}
• 关键词：Nodal ; Cerl2 ; Arl13b ; Left&ndash ; right axis
• 刊名：Developmental Biology
• 出版年：2012
• 期刊代码：167_00121606
• 类别：bio
• 出版时间：1 July, 2012
• 卷：367
• 期：1
• 页码：15-24
• 文件大小：1399 K

摘要

Specification of the left-right axis during embryonic development is critical for the morphogenesis of asymmetric organs such as the heart, lungs, and stomach. The first known left-right asymmetry to occur in the mouse embryo is a leftward fluid flow in the node that is created by rotating cilia on the node surface. This flow is followed by asymmetric expression of <em>Nodalem> and its inhibitor <em>Cerl2em> in the node. Defects in cilia and/or fluid flow in the node lead to defective <em>Nodalem> and <em>Cerl2em> expression and therefore incorrect visceral organ situs. Here we show the cilia protein <em>Arl13bem> is required for left right axis specification as its absence results in heterotaxia. We find the defect originates in the node where <em>Cerl2em> is not downregulated and asymmetric expression of <em>Nodalem> is not maintained resulting in symmetric expression of both genes. Subsequently, <em>Nodalem> expression is delayed in the lateral plate mesoderm (LPM). Symmetric <em>Nodalem> and <em>Cerl2em> in the node could result from defects in either the generation and/ or the detection of <em>Nodalem> flow, which would account for the subsequent defects in the LPM and organ positioning.