Document Type
Article
Publication Date
11-1-2014
Publication Title
Journal of the American Society of Nephrology
Abstract
Odd-skipped related 1 (Osr1) encodes a zinc finger transcription factor required for kidney development. Osr1 deficiency in mice results in metanephric kidney agenesis, whereas knockdown or mutation studies in zebrafish revealed that pronephric nephrons require osr1 for proximal tubule and podocyte development. osr1-deficient pronephric podocyte progenitors express the Wilms' tumor suppressor wt1a but do not undergo glomerular morphogenesis or express the foot process junctional markers nephrin and podocin. The function of osr1 in podocyte differentiation remains unclear, however. Here, we found by double fluorescence in situ hybridization that podocyte progenitors coexpress osr1 and wt1a. Knockdown of wt1a disrupted podocyte differentiation and prevented expression of osr1. Blocking retinoic acid signaling, which regulates wt1a, also prevented osr1 expression in podocyte progenitors. Furthermore, unlike the osr1-deficient proximal tubule phenotype, which can be rescued by manipulation of endoderm development, podocyte differentiation was not affected by altered endoderm development, as assessed by nephrin and podocin expression in double osr1/sox32-deficient embryos. These results suggest a different, possibly cell-autonomous requirement for osr1 in podocyte differentiation downstream of wt1a. Indeed, osr1-deficient embryos did not exhibit podocyte progenitor expression of the transcription factor lhx1a, and forced expression of activated forms of the lhx1a gene product rescued nephrin expression in osr1-deficient podocytes. Our results place osr1 in a framework of transcriptional regulators that control the expression of podocin and nephrin and thereby mediate podocyte differentiation.
Volume
25
Issue
11
First Page
2539
Last Page
2545
DOI
10.1681/ASN.2013121327
ISSN
10466673
Rights
© 2014 by the American Society of Nephrology
Recommended Citation
Tomar, Ritu; Mudumana, Sudha P.; Pathak, Narendra; Hukriede, Neil A.; and Drummond, Iain A., "osr1 Is Required for Podocyte Development Downstream of wt1a" (2014). Neuroscience: Faculty Publications, Smith College, Northampton, MA.
https://scholarworks.smith.edu/nsc_facpubs/32
Comments
Archived as published. Open access article.