Cervino Ailen S, Collodel Mariano G, Lopez Ivan A, Hochbaum Daniel, Hukriede Neil A, Cirio M Cecilia
bioRxiv. 2023 Apr 16:2023.04.15.537039. doi: 10.1101/2023.04.15.537039.
The nephron, functional unit of the vertebrate kidney, is specialized in metabolic wastes excretion and body fluids osmoregulation. Given the high evolutionary conservation of gene expression and segmentation patterning between mammalian and amphibian nephrons, the pronephric kidney offers a simplified model for studying nephrogenesis. The Lhx1 transcription factor plays several roles during embryogenesis, regulating target genes expression by forming multiprotein complexes with LIM binding protein 1 (Ldb1). However, few Lhx1-Ldb1 cofactors have been identified for kidney organogenesis. By tandem-affinity purification from kidney-induced animal caps, we identified s ingle- s tranded DNA b inding p rotein 2 (Ssbp2) interacts with the Ldb1-Lhx1 complex. Ssbp2 is expressed in the pronephros, and knockdown prevents normal morphogenesis and differentiation of the glomus and the convoluted renal tubules. We demonstrate a role for a member of the Ssbp family in kidney organogenesis and provide evidence of a fundamental function for the Ldb1-Lhx1-Ssbp transcriptional complexes in embryonic development.
肾单位是脊椎动物肾脏的功能单位,专门负责代谢废物的排泄和体液的渗透压调节。鉴于哺乳动物和两栖动物肾单位之间基因表达和分段模式具有高度的进化保守性,前肾提供了一个研究肾发生的简化模型。Lhx1转录因子在胚胎发育过程中发挥多种作用,通过与LIM结合蛋白1(Ldb1)形成多蛋白复合物来调节靶基因的表达。然而,在肾脏器官发生过程中,很少有Lhx1-Ldb1辅因子被鉴定出来。通过从肾脏诱导的动物帽中进行串联亲和纯化,我们鉴定出单链DNA结合蛋白2(Ssbp2)与Ldb1-Lhx1复合物相互作用。Ssbp2在前肾中表达,敲低它会阻止肾小球和迂曲肾小管的正常形态发生和分化。我们证明了Ssbp家族的一个成员在肾脏器官发生中的作用,并为Ldb1-Lhx1-Ssbp转录复合物在胚胎发育中的基本功能提供了证据。