A Secreted BMP Antagonist, Cer1, Fine Tunes the Spatial Organization of the Ureteric Bud Tree during Mouse Kidney Development

被引：31

作者：

Chi, Lijun ^{[1
]}

Saarela, Ulla ^{[1
]}

Railo, Antti ^{[1
]}

Prunskaite-Hyyrylainen, Renata ^{[1
]}

Skovorodkin, Ilya ^{[1
]}

Anthony, Shelagh ^{[2
]}

Katsu, Kenjiro ^{[3
]}

Liu, Yu ^{[4
]}

Shan, Jingdong ^{[1
]}

Salgueiro, Ana Marisa ^{[5
,6
]}

Belo, Jose Antonio ^{[5
,6
]}

Davies, Jamie ^{[2
]}

Yokouchi, Yuji ^{[3
]}

Vainio, Seppo J. ^{[1
]}

机构：

[1] Univ Oulu, Bioctr Oulu, Ctr Cell Matrix Res,Inst Biomed Oulu, Lab Dev Biol,Dept Med Biochem & Mol Biol, Oulu, Finland

[2] Univ Edinburgh, Ctr Integrat Physiol, Edinburgh, Midlothian, Scotland

[3] Kumamoto Univ, Div Pattern Format, Dept Organogenesis, Inst Mol Embryol & Genet, Kumamoto, Japan

[4] Texas A&M Hlth Sci Ctr, Ctr Dev & Dis, Inst Biosci & Technol, Houston, TX USA

[5] Univ Algarve, Dept Ciencias Biomed & Med, Regenerat Med Program, Algarve, Portugal

[6] Univ Algarve, IBB, Ctr Biomed Mol & Estrutural, Faro, Portugal

来源：

PLOS ONE | 2011年 / 6卷 / 11期

基金：

芬兰科学院; 英国医学研究理事会;

关键词：

BONE MORPHOGENETIC PROTEIN; RENAL BRANCHING MORPHOGENESIS; METANEPHRIC MESENCHYME; EPITHELIAL TRANSFORMATION; CERBERUS-LIKE; EXPRESSION; GENE; SIGNALS; REGULATOR; PATHWAYS;

D O I：

10.1371/journal.pone.0027676

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

The epithelial ureteric bud is critical for mammalian kidney development as it generates the ureter and the collecting duct system that induces nephrogenesis in dicrete locations in the kidney mesenchyme during its emergence. We show that a secreted Bmp antagonist Cerberus homologue (Cer1) fine tunes the organization of the ureteric tree during organogenesis in the mouse embryo. Both enhanced ureteric expression of Cer1 and Cer1 knock out enlarge kidney size, and these changes are associated with an altered three-dimensional structure of the ureteric tree as revealed by optical projection tomography. Enhanced Cer1 expression changes the ureteric bud branching programme so that more trifid and lateral branches rather than bifid ones develop, as seen in time-lapse organ culture. These changes may be the reasons for the modified spatial arrangement of the ureteric tree in the kidneys of Cer1+ embryos. Cer1 gain of function is associated with moderately elevated expression of Gdnf and Wnt11, which is also induced in the case of Cer1 deficiency, where Bmp4 expression is reduced, indicating the dependence of Bmp expression on Cer1. Cer1 binds at least Bmp2/4 and antagonizes Bmp signalling in cell culture. In line with this, supplementation of Bmp4 restored the ureteric bud tip number, which was reduced by Cer1+ to bring it closer to the normal, consistent with models suggesting that Bmp signalling inhibits ureteric bud development. Genetic reduction of Wnt11 inhibited the Cer1-stimulated kidney development, but Cer1 did not influence Wnt11 signalling in cell culture, although it did inhibit the Wnt3a-induced canonical Top Flash reporter to some extent. We conclude that Cer1 fine tunes the spatial organization of the ureteric tree by coordinating the activities of the growth-promoting ureteric bud signals Gndf and Wnt11 via Bmp-mediated antagonism and to some degree via the canonical Wnt signalling involved in branching.

引用

页数：16

共 85 条

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