Mouse Limb Bud Skeletal Patterning Description and Modelling

Understanding how complex organs reliably form during development remains a key question in biology. In this talk, I discuss how gene regulatory networks may generate skeletal patterns in the vertebrate limb, using Sox9 expression as a proxy, as it marks the earliest stages of cartilage formation. To address this, I developed new computational tools for reconstructing spatiotemporal gene expression and built models ranging from machine learning approaches to mechanistic frameworks. These analyses reveal that limb patterning cannot be explained by a single universal mechanism. Instead, different regions of the limb appear to use distinct regulatory strategies, uncovering an unexpected qualitative modularity in skeletal development. Together, these findings lead to a new hypothesis in which other systems, such as the vasculature may actively shape skeletal spacing in specific limb regions.