My work concerns a critical question: How did the cellular mechanisms underpinning animal morphogenesis first evolve? While the first multicellular ancestors of modern animals have left limited fossil traces, insights can be gained by studying their closest living relatives: the choanoflagellates. These microeukaryotes have several features of unique relevance to animal origins, including temporal cell differentiation, facultative multicellularity, and a metazoan-like ‘developmental gene toolkit’. Moreover, they have become amenable to functional genetics in the past few years. We will study the molecular and cellular mechanisms of three morphogenetic transitions in choanoflagellates: (1) the formation of the “collar complex”, a ring of microvilli surrounding the flagellum, which represents an example of complex single-cell morphogenesis and plays a central role in hypotheses on early animal evolution; (2) the molecular control of the transdifferentiation of choanoflagellates into amoeboid cells under confinement, which I recently discovered and whose mechanisms remain unknown; (3) the cellular basis of adhesion and inversion in sheet colonies of the multicellular species Choanoeca flexa, which I co-discovered. These 3 processes will be characterized by omic approaches (transcriptomics, proteomics, phosphoproteomics and lipidomics) which will allow unbiased comparisons with the growing dataset of molecular atlases for animal cell types. We will perform knockout, chemical inhibition, and fluorescent tagging of defined candidate genes identified by omics and/or known to play important roles in animals – including both structural genes (such as cytoskeletal and adhesion molecules) and signalling molecules. This project has the potential to illuminate long-standing questions on the pre-metazoan function of developmental genes and to inform the mechanistic basis of the transition from cells to organisms in both development and evolution.
