OriCellDiff · Deciphering the origins of cell differentiation and developmental gene regulation in animals

During animal development the process of cell differentiation gives rise to terminally differentiated cell types with cell-type-specific gene expression programs. In the most closely related group to animals, the choanoflagellates, cell differentiation occurs but cells do not commit irreversibly to specific fates. Instead, they transition through cell identities as they progress through their life cycle, known as temporal cell differentiation. Animal cell differentiation is thought to have evolved from temporal differentiation, but the mechanisms are largely unknown due to a lack of information on the molecular processes underpinning temporal differentiation.This proposal will test the hypothesis that chromatin-based transcriptional regulation underlies temporal cell differentiation in choanoflagellates. Utilizing S. rosetta as a model, I will compare transcription and chromatin across cell types using genome-wide omics techniques. This will allow me to assess the role of different histone modifications in cell-fate transitions and discover whether various aspects of animal developmental gene regulation, e.g., the use of repressive histone modifications in cell-type-specific gene regulation, are also utilised in choanoflagellates. I will also examine the cis-regulatory landscape in S. rosetta and use both molecular and functional assays to examine the types of cis-regulatory elements present, and particularly if enhancer elements are used to regulate gene expression. Finally, I will test the role of selected chromatin regulators in temporal cell differentiation and cell-type-specific gene expression. This ground-breaking work will be the first to study these processes in choanoflagellates, thus pioneering the comparison between definitive cell differentiation, seen in animals, and choanoflagellate temporal differentiation. In a broader context, this will deliver fundamental new insights into the evolution of animal gene-regulation during development.