Isl2b regulates anterior second heart field development in zebrafish

Hagen R Witzel,Rui Gao,Didier Y R Stainier,Gergana D Dobreva,Sirisha Cheedipudi

doi:10.1038/srep41043

Abstract

After initial formation, the heart tube grows by addition of second heart field progenitor cells to its poles. The transcription factor Isl1 is expressed in the entire second heart field in mouse, and Isl1-deficient mouse embryos show defects in arterial and venous pole development. The expression of Isl1 is conserved in zebrafish cardiac progenitors; however, Isl1 is required for cardiomyocyte differentiation only at the venous pole. Here we show that Isl1 homologues are expressed in specific patterns in the developing zebrafish heart and play distinct roles during cardiac morphogenesis. In zebrafish, isl2a mutants show defects in cardiac looping, whereas isl2b is required for arterial pole development. Moreover, Isl2b controls the expression of key cardiac transcription factors including mef2ca, mef2cb, hand2 and tbx20. The specific roles of individual Islet family members in the development of distinct regions of the zebrafish heart renders this system particularly well-suited for dissecting Islet-dependent gene regulatory networks controlling the behavior and function of second heart field progenitors in distinct steps of cardiac development.

Highlights

The heart is generated by distinct progenitor cell populations, which have specific regional contributions to the developing heart
Islet family members are expressed in distinct patterns in the developing zebrafish heart
To characterize whether other Islet family members may play a role in arterial pole development during zebrafish cardiogenesis, we performed immunostaining of Tg(myl7:EGFP-HsHRAS)s883 embryos, that expresses membrane-bound GFP under the control of the myl[7] promoter in all differentiated cardiomyocytes, and isl1−/−Tg(myl7:EGFP-HsHRAS)s883 embryos, using an antibody recognizing both Isl[1] and Isl[2] proteins[18,20,21] (Fig. 1)

Summary

Introduction

The heart is generated by distinct progenitor cell populations, which have specific regional contributions to the developing heart. We still detected residual Isl1/2-positive cells at the arterial pole of the heart and the inner curvature of the ventricle (Fig. 1c).

Results

Conclusion