Functional genomics and the evolutionary diversification of the artiodactyl limb

Resumen del póster presentado a la 14th International Limb Development and Regeneration Conference, celebrada en Edimburgo (UK) del 23 al 26 de julio de 2017.-- et al.Recent efforts in mapping the regulatory genome have uncovered that loci with essential functions in development typically contain complex cis‐regulatory landscapes. Such complexity is required to achieve precise spatio‐temporal control of gene expression, as developmental genes are frequently required in several tissues and time points. A general concept in the field is that alterations in the regulation of these pleiotropic and conserved developmental genes are a main mechanism underlying the evolution of morphology. Morphogenesis of the vertebrate limb is a genetically well‐understood process that can be used as a paradigm to gain insight into the mechanisms of transcriptional regulation during both developmental and evolutionary processes. The pig (Sus scrofa), a new arising model in biomedical research, is an artiodactyl (even‐toe ungulate) in which the extremities are specialized for cursorial locomotion, thanks to various modifications of the distal limb skeleton. The pig limb displays loss and reduction of digits, which are largely symmetrical, elongated and with hoofed phalanges. Here we report a detailed morphological and molecular analysis of pig limb development. In particular, we have analyzed the expression of several genes with essential functions in patterning and growth of the limb bud, such as 5'Hoxd genes and components of the SHH, BMP and FGF signaling pathways and their transcriptional targets. These studies have revealed that the pig limb bud displays a loss of anterior‐posterior polarity in the distal mesenchyme that contains the digit progenitor cells. In addition, we have combined transcriptomics in pig and mouse limb buds with the cataloging of regions with regulatory potential using ATAC‐seq, which identifies regions of open chromatin. The ultimate aim of our studies is to determine if evolutionary alterations in the cis‐regulatory networks that control limb development have contributed to the acquisition of specific morphological traits observed in the pig appendicular skeleton.Peer reviewe