PIF2024 - The Limb Dorsoventral Axis: Investigating Lmx1b role in Development, Evolution, and Regeneration (PID2023-147771NB-I00)

Our project aspires to make substantial breakthroughs in our understanding of how the genome encodes morphology and organ shape. Limb development and patterning has been intensely studied resulting in a ample body of knowledge that sets the basis to assess changes in gene function with distinct phenotypic outcomes. Recent studies have identified changes in chromosome structure that impact gene regulatory dynamics as causes of limb disorders in patients as well as a potential source of the limb variations observed in nature. The evolution of the limb from an ancestral fin structure, the fin-to-limb transition, is a well-studied morphological transition in vertebrate evolution. Moreover, the limb provides a unique system to unravel the mechanisms that govern tissue regrowth and repair. Thus, the limb is a robust model for exploring in detail how gene regulation impacts on morphology and how modifications to gene regulatory logic can result in innovative forms and functions. Building upon our previous findings highlighting the complexity of the Lmx1b regulatory locus in DV limb polarity, here we propose a multidisciplinary strategy that integrates genomic analyses and functional genetics to explore how the regulatory hardwiring of the Lmx1b locus impact development and regeneration potential. The overarching goal is to unravel how the regulatory logic of cis-regulatory cassettes provides the context for morphological shape and developmental potential as observed in regeneration