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American Heart Association

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Final ID: We080

Mapping the effect of Hedgehog signaling on cardiac differentiation and migration in space and time

Abstract Body: Background
Organ morphogenesis requires precise control of organ-specific progenitor cell migration and differentiation. Hedgehog signaling is a major signaling pathway during animal development and is essential for proper cardiac development. Previous work demonstrated that Hedgehog signaling can regulate migration and the timing of differentiation of cardiac progenitors. However, how Hedgehog signaling integrates control of differentiation timing and migration in space to enable proper organ formation during development remains unclear.

Hypothesis
We hypothesize that Hedgehog signaling explicitly controls cardiac morphogenesis by coordinating cellular migration and differentiation of cardiac progenitors to determining where and when they turn into cardiomyocytes.

Methods
We combine mouse genetics, in-vivo lineage tracing, whole mouse embryo light-sheet imaging, and metanalysis of publicly available spatial transcriptomics datasets to address the hypothesis.

Results
We identified the sites of active Hedgehog signaling by studying a reporter for Hedgehog signaling (GBS-GFP). Next, we determined the necessity of Hedgehog signaling for differentiation of cardiomyocytes at the right place and time by tracing the cardiac progenitors over developmental time in mutants in controls compared to Hedgehog signaling mutants.

Conclusion and future directions
This work will establish the dual role of Hedgehog signaling in differentiation timing and migration control as a novel paradigm that may be generalizable to other organ systems dependent on Hedgehog signaling (e.g., neural cord and limb patterning).
  • Tarampoulous, Isaak  ( The University of Chicago , Chicago , Illinois , United States )
  • Leo Justin, Avryn  ( The University of Chicago , Chicago , Illinois , United States )
  • Ponnuswamy, Kirthi  ( The University of Chicago , Chicago , Illinois , United States )
  • Lariviere, Patrick  ( The University of Chicago , Chicago , Illinois , United States )
  • Moskowitz, Ivan  ( The University of Chicago , Chicago , Illinois , United States )
  • Author Disclosures:
    Isaak Tarampoulous: DO NOT have relevant financial relationships | Avryn Leo Justin: No Answer | Kirthi Ponnuswamy: No Answer | Patrick LaRiviere: No Answer | Ivan Moskowitz: No Answer
Meeting Info:

Basic Cardiovascular Sciences

2024

Chicago, Illinois

Session Info:

Poster Session and Reception 3

Wednesday, 07/24/2024 , 04:30PM - 07:00PM

Poster Session and Reception

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