Drummond Bridgette E, Chambers Brooke E, Wesselman Hannah M, Gibson Shannon, Arceri Liana, Ulrich Marisa N, Gerlach Gary F, Kroeger Paul T, Leshchiner Ignaty, Goessling Wolfram, Wingert Rebecca A
Department of Biological Sciences, Center for Stem Cells and Regenerative Medicine, Center for Zebrafish Research, University of Notre Dame, Notre Dame, IN 46556, USA.
Brigham and Women's Hospital, Genetics and Gastroenterology Division, Harvard Medical School, Harvard Stem Cell Institute, Boston, MA 02215, USA.
Biomedicines. 2022 Nov 9;10(11):2868. doi: 10.3390/biomedicines10112868.
Knowledge about the genetic pathways that control nephron development is essential for better understanding the basis of congenital malformations of the kidney. The transcription factors Osr1 and Hand2 are known to exert antagonistic influences to balance kidney specification. Here, we performed a forward genetic screen to identify nephrogenesis regulators, where whole genome sequencing identified an lesion in the novel () mutant. The characterization of the mutant revealed that is needed to specify not renal progenitors but rather their maintenance. Additionally, promotes the expression of in the intermediate mesoderm (IM) and later the podocyte lineage. deficiency reduced podocytes, where overexpression of was sufficient to rescue podocytes and deficiency. Antagonism between and mediates podocyte development specifically by controlling expression. These studies reveal new insights about the roles of Osr1 in promoting renal progenitor survival and lineage choice.
了解控制肾单位发育的遗传途径对于更好地理解先天性肾脏畸形的基础至关重要。已知转录因子Osr1和Hand2发挥拮抗作用以平衡肾脏特化。在此，我们进行了一项正向遗传筛选以鉴定肾发生调节因子，全基因组测序在新型（）突变体中鉴定出一个损伤。对该突变体的表征表明，（此处原文缺失关键基因名称）并非用于指定肾祖细胞，而是用于其维持。此外，（此处原文缺失关键基因名称）促进中间中胚层（IM）中（此处原文缺失关键基因名称）的表达，随后促进足细胞谱系中的表达。（此处原文缺失关键基因名称）缺陷减少了足细胞，而（此处原文缺失关键基因名称）的过表达足以挽救足细胞和（此处原文缺失关键基因名称）缺陷。（此处原文缺失关键基因名称）和（此处原文缺失关键基因名称）之间的拮抗作用通过控制（此处原文缺失关键基因名称）表达特异性地介导足细胞发育。这些研究揭示了关于Osr1在促进肾祖细胞存活和谱系选择中的作用的新见解。
