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Abstract: PO0618

OSR1 Couples Intermediate Mesoderm Cell Fate with Temporal Dynamics of Vessel Progenitor Cell Differentiation

Session Information

Category: Development, Stem Cells, and Regenerative Medicine

  • 500 Development, Stem Cells, and Regenerative Medicine

Authors

  • Perens, Elliot, University of California San Diego, La Jolla, California, United States
  • Diaz, Jessyka, University of California San Diego, La Jolla, California, United States
  • Yelon, Deborah, University of California San Diego, La Jolla, California, United States
Background

Transcriptional regulatory networks refine gene expression boundaries throughout embryonic development to define the precise dimensions of organ progenitor territories. Kidney progenitors originate within the intermediate mesoderm (IM), but the pathways that establish the boundary between the IM and its neighboring vessel progenitors are poorly understood.

Methods

We employ a combination of loss-of-function and gain-of-function genetics, RNA in situ hybridization, immunohistochemisty, and transgensis in the zebrafish model system.

Results

Here, we delineate new roles for the zinc finger transcription factor Osr1 in kidney and vessel progenitor development. Zebrafish osr1 mutants display decreased IM formation and premature emergence of neighboring lateral vessel progenitors (LVPs). These phenotypes contrast with the increased IM and absent LVPs observed with loss of the bHLH transcription factor Hand2, and loss of hand2 partially suppresses the osr1 mutant phenotypes. hand2 and osr1 are both expressed in the posterior lateral mesoderm, but osr1 expression decreases dramatically prior to LVP emergence. Induction of osr1 expression after gastrulation is sufficient for inhibiting LVP development and rescuing IM and pronephron formation.

Conclusion

Together, our data demonstrate that osr1 modulates both the extent of IM formation and the temporal dynamics of LVP development, suggesting that a balance between levels of osr1 and hand2 expression is essential to demarcate the dimensions of kidney and vessel progenitor territories.

Funding

  • NIDDK Support