Conserved and species-specific chromatin remodeling and regulatory dynamics during mouse and chicken limb bud development

The vertebrate limb bud is a paradigm to uncover the fundamental mechanisms that govern embryogenesis and evolutionary diversification. Here the authors compare mouse and chicken limb bud development to study the impact of genome evolution on conserved and divergent gene regulatory interactions. Chromatin remodeling and genomic alterations impact spatio-temporal regulation of gene expression, which is central to embryonic development. The analysis of mouse and chicken limb development provides important insights into the morphoregulatory mechanisms, however little is known about the regulatory differences underlying their morphological divergence. Here, we identify the underlying shared and species-specific epigenomic and genomic variations. In mouse forelimb buds, we observe striking synchrony between the temporal dynamics of chromatin accessibility and gene expression, while their divergence in chicken wing buds uncovers species-specific regulatory heterochrony. In silico mapping of transcription factor binding sites and computational footprinting establishes the developmental time-restricted transcription factor-DNA interactions. Finally, the construction of target gene networks for HAND2 and GLI3 transcriptional regulators reveals both conserved and species-specific interactions. Our analysis reveals the impact of genome evolution on the regulatory interactions orchestrating vertebrate limb bud morphogenesis and provides a molecular framework for comparative Evo-Devo studies.

Automated summary

This study compared mouse and chicken limb bud development to investigate the impact of genome evolution on gene regulatory interactions, revealing the importance of spatio-temporal regulation of gene expression in embryonic development. The authors identified shared and species-specific epigenomic and genomic variations, and observed synchrony in chromatin accessibility and gene expression dynamics in mouse forelimb buds, while uncovering species-specific regulatory heterochrony in chicken wing buds. Mapping of transcription factor binding sites and construction of target gene networks revealed both conserved and species-specific interactions, providing a molecular framework for comparative Evo-Devo studies.