The Department of Biomedicine

BBB webinar: Lionel Christiaen

An extended central dogma for developmental cellular systems

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Lionel Christiaen
Sars International Centre for Marine Molecular Biology, University of Bergen, and Department of Biology, New York University, NY, USA

During animal development, generations of cells progressively acquire successive identities, typically transitioning from pluripotent stem cells, to multipotent progenitors, fate-restricted precursors and terminally differentiated cells. At every stage, these fate decisions are coupled with defined cellular behaviors that underlie tissue morphogenesis and eventually organogenesis. These notions imply that shared regulatory mechanisms couple cell fate decisions and cellular behaviors, at the cellular systems level. We thus propose to formalize these concepts into "an extended central dogma for developmental cellular systems".

To study regulatory mechanisms coupling cell fate decisions and cellular behaviors, we have been focusing on the cardiopharyngeal lineage, which produces both first and second heart lineages, and pharyngeal muscles (aka branchiomeric head muscles) from common multipotent progenitors. Circumventing the complexity of early vertebrate embryos, we leveraged the unique features of their closest relatives, the tunicate Ciona, a powerful marine model with simple and tractable embryos. In Ciona, the cardiopharyngeal lineage consists of two pairs of multipotent progenitors that migrate collectively on either side of the embryo, before dividing twice in a stereotyped oriented and asymmetric manner to produce first and second heart lineages, and pharyngeal muscle precursors. Using this simple model, we uncovered general principles governing a variety of regulatory mechanisms and cellular processes ranging from chromatin accessibility and gene expression dynamics, to cell-cell signaling, cell matrix adhesion and the biophysics of cell shape and movements.

Here, I will present (1) a single cell genomics approach leveraging transgene barcoding to characterize gene expression dynamics in migratory cells at high (pseudo-)temporal resolution in a multiplexed assay, (2) an integrative approach combining mathematical modeling and experimental perturbations to uncover biophysical features of migrating cardiopharyngeal progenitors; to finish, I will present (3) ongoing work coupling systematic CRISPR/Cas9-mediated loss-of-function assays with high-content quantitative image analysis, and data science techniques, to generate provisional models of the biochemical network underlying cellular behavior. We argue that this integrated multipronged approach permits in-depth analysis of the various components of cardiopharyngeal lineage development.

Chairperson: Nils Halberg, Department of Biomedicine