Seed funding - Convergent Cell Fate Decisions and Skeletal Patterning at Evolutionary, Embryonic and Single Cell Resolution

The concept of 'cell fate', central to both developmental biology and regenerative medicine, has seen dramatic shifts in recent years. Thanks to emerging single-cell technologies and cellular (re-)programming, we are now able to address questions resulting therefrom at unprecedented detail. While many studies have focused on the emergence of cellular diversity from a single precursor type, there are instances where distinct embryonic progenitor pools converge to give rise to functionally analogous cell types. What is the gene regulatory logic underlying such cell fate convergence? And how amenable are these transcriptional networks to evolutionary change, to result in distinct, species-specific morphologies? Here, I propose an integrative approach to elucidate this question using vertebrate skeletogenesis as a model system, over developmental and evolutionary timescales, at lineage- and single-cell resolution, during cell fate convergence and embryonic pattern formation. Building on my expertise in comparative transcriptomics and developmental biology, we will (1) study the gene regulatory logic of analogous cell fate specification from three distinct embryonic progenitor pools; (2) delineate the essential core regulatory nodes through a deep sampling of the vertebrate phylogeny and functionally test them via targeted in vitro specifications; and, ultimately, (3) integrate these insights to investigate species- specific and patterning-relevant in vivo cell fate decisions using single-cell RNA-sequencing and mathematical modeling. Collectively, our work will define core regulatory networks that specify a given skeletal cell fate across developmental and evolutionary levels, during cell fate convergence and embryonic patterning. As such, it will help to define novel paradigms of developmental cell fate decision control, for the skeletal system and beyond, and open new avenues for regenerative medicine.