Department of Anatomy and Developmental Biology, Monash University, Clayton, Victoria, Australia.
PLoS One. 2011 Apr 18;6(4):e18723. doi: 10.1371/journal.pone.0018723.
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.
β 聚糖是转化生长因子-β（TGFβ）超家族的辅助受体，该超家族的许多成员在肾脏发育中发挥关键作用。本研究旨在确定该共受体在胎鼠肾脏发育中的作用。对胚胎期和成年期β 聚糖杂合子肾脏的体视学检查显示，相对于同窝对照，肾小球数量增加。胎儿杂合子肾脏的输尿管分支加速，这与胚胎期 15.5 天（e）时肾小球发育增加有关。相比之下，β 聚糖缺失肾脏从 e13.5 开始出现肾发育不全，并且在 e15.5 时肾小球数量减少。对 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 Bmp4 表达短暂下降，随后是调控后肾发育的基因调控网络的级联变化，包括 Pax2、Eya1、Gdnf、Ret、Wnt4 和 Wt1 表达的显著增加。相反，缺失肾脏的基因表达在 e13.5 之前是正常的，此时 Bmp4 以及其他关键后肾调控基因的表达明显减少。Tgfb1 和 Tgfb2mRNA 表达在 e13.5 和 e14.5 时在缺失体和杂合体中均下调。β 聚糖杂合子和缺失突变体在形态和分子表型上的相反表现表明，β 聚糖的水平必须严格调控以实现最佳的肾脏发育。
