University of Cambridge > > Morphogenesis Seminar Series > Holly Lovegrove: Mitosis in Motion: Cell division during collective cell migration; Leo Otsuki: Puzzling out tissue regeneration.

Holly Lovegrove: Mitosis in Motion: Cell division during collective cell migration; Leo Otsuki: Puzzling out tissue regeneration.

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Holly Lovegrove: Mitosis in Motion: Cell division during collective cell migration

The complexities of cell division have been extensively studied, as such there is a wealth of knowledge concerning the processes required to carry it out. However, the majority of this work has been carried out in simple, in vitro, single cell systems. While this knowledge is invaluable it does not consider how cell division is conducted in the more complex, dynamic and multicellular environments found in vivo.

In order to perform their specialised functions cells within tissues are arranged into specific architectures, to achieve them requires the careful manipulation of a range of cellular features (e.g. cell-cell adhesion, cell polarity, cell shape). Cell division however is highly dynamic, for example requiring dramatic rearrangements of the cytoskeleton. It therefore has the potential to be highly disruptive and poses a particular challenge to many crucial features of tissues during their generation and maintenance.

These challenges are particulary acute in tissues undergoing collective migration, as the highly dynamic and motile nature of these systems creates extra layers of complexity. Our work investigates these challenges and the mechanisms cells have developed to overcome them, primarily using high temporal and spatial live imaging of blood vessel development in zebrafish embryos.

Leo Otsuki: Puzzling out tissue regeneration

One goal of regeneration research is to engineer patterned tissues that function in vivo. Regenerative organisms, such as axolotls (Mexican salamanders), could inspire strategies to achieve this using endogenous cells. Axolotls regenerate tissues including limbs, nervous system and jaw despite possessing an anatomy and coding gene complement comparable to humans. One requirement for regenerating limb is that anterior and posterior progenitor cells are co-recruited from the stump to the injury site. Regeneration fails if either cell population is missing. Meanwhile, grafting posterior cells to the anterior side of a limb (or vice versa) under appropriate conditions is sufficient to grow out an extra (‘accessory’) limb without amputation. Thus, axolotl cells harbour positional values and, when compatible, combine like jigsaw pieces to generate functional tissue.

We discovered that the expression of HAND2 transcription factor demarcates posterior progenitors in the axolotl limb. We found that HAND2 is necessary and sufficient to express SHH , a posterior pro-regenerative morphogen during regeneration, and that SHH reciprocally feeds back to maintain HAND2 expression in nearby cells. This HAND2 -SHH positive feedback cycle could explain how posterior identity is stably maintained for regenerative purposes, while also providing an opportunity to alter progenitor identities for synthetic or therapeutic applications. By transiently treating anterior progenitors with SHH , we were able to trigger the HAND2 -SHH loop and overwrite anterior cells with a stable posterior identity. These posteriorized progenitor cells could subsequently express SHH during regeneration. Our results reveal in-routes to tissue engineering by understanding positional values in vertebrate tissues.

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This talk is part of the Morphogenesis Seminar Series series.

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