Maelys Besomi

Investigating the cellular processes underlying digit morphogenesis during normal development and in congenital malformations

 

The mouse limb bud is a fantastic model for investigating organogenesis and gene regulatory networks. It enables the study of both congenital malformations and the evolutionary diversification of tetrapod limbs, which shifted from ancestral polydactyly to dominant pentadactyly. Spatial variation in key genes, such as Grem1, contributes to both evolutionary differences and developmental disorders. Signaling pathways including BMP, SHH, and FGF form regulatory networks essential for proper limb patterning, and disruption of these pathways can cause severe malformations, as seen with Grem1 deletion–induced oligodactyly.

Digit specification occurs by embryonic day 9.5 (E9.5) and the target populations are Limb bud Mesenchymal Progenitors (LMPs), which will give rise to osteochondrogenic lineages.

My project aims to bridge the gap between LMP specification and their progenitor differentiation and I am currently addressing the question by analysing LMP descendants using lineage tracing in wild-type and mutant mice.