Related Experiment Video

Updated: Aug 22, 2025

Guided Differentiation of Mature Kidney Podocytes from Human Induced Pluripotent Stem Cells Under Chemically Defined Conditions
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osr1 Maintains Renal Progenitors and Regulates Podocyte Development by Promoting wnt2ba via the Antagonism of hand2

Bridgette E Drummond1, Brooke E Chambers1, Hannah M Wesselman1

  • 1Department of Biological Sciences, Center for Stem Cells and Regenerative Medicine, Center for Zebrafish Research, University of Notre Dame, Notre Dame, IN 46556, USA.

Biomedicines
|November 11, 2022
PubMed

Insights

The Osr1 gene maintains kidney progenitor cells and promotes Wnt2ba expression, crucial for podocyte development. This Osr1 and Hand2 antagonism offers new insights into congenital kidney malformations.

Area of Science:

  • Developmental Biology
  • Genetics
  • Nephrology

Background:

  • Congenital kidney malformations stem from disrupted nephron development.
  • Transcription factors Osr1 and Hand2 balance kidney specification through antagonistic actions.

Purpose of the Study:

  • Identify novel regulators of nephrogenesis using forward genetics.
  • Elucidate the specific roles of Osr1 in kidney development and its interaction with Hand2.

Main Methods:

  • Forward genetic screen in a zebrafish model.
  • Whole genome sequencing to identify genetic mutations.
  • Analysis of gene expression (Osr1, Hand2, wnt2ba) and cell lineage tracing.

Main Results:

  • A novel mutant, oceanside (ocn), revealed an osr1 lesion essential for renal progenitor maintenance, not initial specification.
  • Osr1 promotes wnt2ba expression in intermediate mesoderm and the podocyte lineage.
  • Wnt2ba deficiency reduced podocytes; its overexpression rescued podocyte defects and osr1 deficiency.

Conclusions:

  • Osr1 is critical for maintaining renal progenitor cells and promoting podocyte development.
  • The antagonism between Osr1 and Hand2 regulates podocyte development via Wnt2ba.
  • These findings provide new understanding of Osr1's role in renal progenitor survival and lineage determination.
Keywords:
developmenthand2kidneynephronosr1podocytewnt2bazebrafish

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