Betaglycan is required for the establishment of nephron endowment in the mouse.
Betaglycan is required for the establishment of nephron endowment in the mouse.
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DOI：
10.1371/journal.pone.0018723
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发表时间：
2011-04-18
期刊：
影响因子：
3.7
通讯作者：
Stenvers KL
中科院分区：
文献类型：
--
作者：
Walker KA;Sims-Lucas S;Caruana G;Cullen-McEwen L;Li J;Sarraj MA;Bertram JF;Stenvers KL
β聚糖是转化生长因子-β（TGFβ）超家族的辅助受体，其中许多成员在肾脏发育中起关键作用。本研究的目的是确定这种辅助受体对胎鼠肾脏发育的作用。体视学检查胚胎和成人β聚糖杂合肾显示增加肾单位数量相对于同窝对照。胎儿杂合子肾脏表现出加速输尿管分支，这与增强肾单位发育在胚胎天（e）15.5。相反，β聚糖缺失的肾脏从e13.5开始表现出肾发育不全，在e15.5时肾单位数量减少。e11.5-e14.5肾脏的定量实时PCR分析表明，杂合子肾脏在e11.5时表现出Bmp 4表达的短暂降低，以及随后控制后肾发育的基因调控网络的级联变化，包括Pax 2、Eya 1、Gdnf、Ret、Wnt 4和Wt 1表达的显著增加。相反，基因表达在空肾是正常的，直到e13.5，当检测到Bmp 4以及其他关键的后肾调节基因的表达显着减少。在e13.5和e14.5，Tgfb 1和Tgfb 2 mRNA表达在无效和杂合子中均下调。β聚糖杂合子和无效突变体中相反的形态学和分子表型证明β聚糖的水平必须严格调节以获得最佳的肾脏发育。
Betaglycan is an accessory receptor for the transforming growth factor-β (TGFβ) superfamily, many members of which play key roles in kidney development. The purpose of this study was to define the role of this co-receptor on fetal murine kidney development. Stereological examination of embryonic and adult betaglycan heterozygous kidneys revealed augmented nephron number relative to littermate controls. Fetal heterozygous kidneys exhibited accelerated ureteric branching, which correlated with augmented nephron development at embryonic day (e) 15.5. In contrast, betaglycan null kidneys exhibited renal hypoplasia from e13.5 and reduced nephron number at e15.5. Quantitative real-time PCR analysis of e11.5–e14.5 kidneys demonstrated that heterozygous kidneys exhibited a transient decrease in Bmp4 expression at e11.5 and a subsequent cascade of changes in the gene regulatory network that governs metanephric development, including significant increases in Pax2, Eya1, Gdnf, Ret, Wnt4, and Wt1 expression. Conversely, gene expression in null kidneys was normal until e13.5, when significant reductions were detected in the expression of Bmp4 as well as other key metanephric regulatory genes. Tgfb1 and Tgfb2 mRNA expression was down-regulated in both nulls and heterozygotes at e13.5 and e14.5. The opposing morphological and molecular phenotypes in betaglycan heterozygote and null mutants demonstrate that the levels of betaglycan must be tightly regulated for optimal kidney development.
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