PUBLICATION
osr1 Maintains Renal Progenitors and Regulates Podocyte Development by Promoting wnt2ba via the Antagonism of hand2
- Authors
- Drummond, B.E., Chambers, B.E., Wesselman, H.M., Gibson, S., Arceri, L., Ulrich, M.N., Gerlach, G.F., Kroeger, P.T., Leshchiner, I., Goessling, W., Wingert, R.A.
- ID
- ZDB-PUB-221115-26
- Date
- 2022
- Source
- Biomedicines 10(11): (Journal)
- Registered Authors
- Chambers, Brooke, Drummond, Bridgette, Gerlach, Gary F., Goessling, Wolfram, Kroeger, Paul, Ulrich, Marisa, Wingert, Rebecca
- Keywords
- development, hand2, kidney, nephron, osr1, podocyte, wnt2ba, zebrafish
- MeSH Terms
- none
- PubMed
- 36359386 Full text @ Biomedicines
Citation
Drummond, B.E., Chambers, B.E., Wesselman, H.M., Gibson, S., Arceri, L., Ulrich, M.N., Gerlach, G.F., Kroeger, P.T., Leshchiner, I., Goessling, W., Wingert, R.A. (2022) osr1 Maintains Renal Progenitors and Regulates Podocyte Development by Promoting wnt2ba via the Antagonism of hand2. Biomedicines. 10(11):.
Abstract
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 osr1 lesion in the novel oceanside (ocn) mutant. The characterization of the mutant revealed that osr1 is needed to specify not renal progenitors but rather their maintenance. Additionally, osr1 promotes the expression of wnt2ba in the intermediate mesoderm (IM) and later the podocyte lineage. wnt2ba deficiency reduced podocytes, where overexpression of wnt2ba was sufficient to rescue podocytes and osr1 deficiency. Antagonism between osr1 and hand2 mediates podocyte development specifically by controlling wnt2ba expression. These studies reveal new insights about the roles of Osr1 in promoting renal progenitor survival and lineage choice.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping