De novo lumen formation and elongation in the developing nephron: a central role for afadin in apical polarity

Author:

Yang Zhufeng1,Zimmerman Susan1,Brakeman Paul R.2,Beaudoin Gerard M.34,Reichardt Louis F.3,Marciano Denise K.1

Affiliation:

1. Department of Medicine, Division of Nephrology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.

2. Departments of Pediatrics, University of California, San Francisco, CA 94158, USA.

3. Physiology, University of California, San Francisco, CA 94158, USA.

4. Institute of Neuroscience, University of Texas at San Antonio, San Antonio, TX 78249, USA.

Abstract

A fundamental process in biology is the de novo formation and morphogenesis of polarized tubules. Although these processes are essential for the formation of multiple metazoan organ systems, little is known about the molecular mechanisms that regulate them. In this study, we have characterized several steps in tubule formation and morphogenesis using the mouse kidney as a model system. We report that kidney mesenchymal cells contain discrete Par3-expressing membrane microdomains that become restricted to an apical domain, coinciding with lumen formation. Once lumen formation has been initiated, elongation occurs by simultaneous extension and additional de novo lumen generation. We demonstrate that lumen formation and elongation require afadin, a nectin adaptor protein implicated in adherens junction formation. Mice that lack afadin in nephron precursors show evidence of Par3-expressing membrane microdomains, but fail to develop normal apical-basal polarity and generate a continuous lumen. Absence of afadin led to delayed and diminished integration of nectin complexes and failure to recruit R-cadherin. Furthermore, we demonstrate that afadin is required for Par complex formation. Together, these results suggest that afadin acts upstream of the Par complex to regulate the integration and/or coalescence of membrane microdomains, thereby establishing apical-basal polarity and lumen formation/elongation during kidney tubulogenesis.

Publisher

The Company of Biologists

Subject

Developmental Biology,Molecular Biology

Reference57 articles.

1. Afadin, a Ras/Rap effector that controls cadherin function, promotes spine and excitatory synapse density in the hippocampus;Beaudoin;J. Neurosci.,2012

2. Control of cell adhesion dynamics by Rap1 signaling;Boettner;Curr. Opin. Cell Biol.,2009

3. Nectin proteins are expressed at early stages of nephrogenesis and play a role in renal epithelial cell morphogenesis;Brakeman;Am. J. Physiol.,2009

4. Atlas of gene expression in the developing kidney at microanatomic resolution;Brunskill;Dev. Cell,2008

5. A molecular network for de novo generation of the apical surface and lumen;Bryant;Nat. Cell Biol.,2010

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3