# Hedgehog and Bmp signaling pathways play opposing roles during establishment of the cardiac inflow tract in zebrafish

## TL;DR

Hedgehog and Bmp signaling pathways control the size of the cardiac inflow tract in zebrafish embryos by acting in opposing ways.

## Contribution

The study reveals that Hh and Bmp signaling have antagonistic roles in regulating IFT cardiomyocyte numbers before differentiation.

## Key findings

- Inhibiting Hh signaling increases the number of IFT cardiomyocytes, while Bmp inhibition reduces it.
- Hh and Bmp signaling act before myocardial differentiation to regulate IFT size.
- Bmp signaling promotes IFT formation via Wnt, while Hh signaling acts independently to restrict IFT size.

## Abstract

Cardiac pacemaking activity is controlled by specialized cardiomyocytes in the cardiac inflow tract (IFT), but the processes that determine IFT dimensions remain poorly understood. Here, we show that Hedgehog (Hh) signaling limits the number of IFT cardiomyocytes in the embryonic zebrafish heart. Inhibiting Hh signaling, either genetically or pharmacologically, results in an expanded IFT population. In contrast, reducing Bmp signaling decreases the number of IFT cardiomyocytes, while increasing Bmp signaling leads to an excess of IFT cardiomyocytes. Temporal inhibition of each pathway reveals that Hh and Bmp signaling act before myocardial differentiation to regulate IFT size. Simultaneous reduction of both Hh and Bmp signaling yields a relatively normal number of IFT cardiomyocytes, suggesting that these pathways function antagonistically during IFT development. Additionally, epistasis analysis suggests that Bmp signaling acts upstream of Wnt signaling to promote IFT formation, whereas Hh signaling limits IFT size in a Wnt-independent manner. Our results support a model in which Hh signaling restricts the establishment of the IFT progenitor pool, while Bmp signaling drives IFT progenitor specification prior to Wnt-directed IFT differentiation.

Summary: Hedgehog signaling acts prior to myocardial differentiation to restrict the number of inflow tract cardiomyocytes, while Bmp signaling acts during a similar timeframe to promote inflow tract cardiomyocyte formation.