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Role of Actßa during development and regeneration


Project Description

TGFβ (Transforming Growth Factor β) superfamily of ligands have been characterised as important players during development, tissue homeostasis, regeneration, wound healing and tumourigenesis. We have recently shown that Actβa, a TGFβ family member, has an important role during blood vessel development in Xenopus tropicalis (Nagamori et al. in prep). Furthermore, analyses of gene expression during regeneration have shown that actβa is massively upregulated both in zebrafish (during fin regeneration) and in Xenopus (during tail regeneration in tadpoles). Despite its importance, the molecular and cellular roles of Actβa are still poorly understood.

This project will have two main aims:

1- Define the role of Actβa during embryonic development and in particular during vasculogenesis.

We have already shown that knocking-down Actβa expression causes vascular malformation. We will establish the molecular mechanisms underlying this phenotype: is it cell autonomous? Does Actβa and VEGF (a well describe pro-angiogenic factor) cooperate for vascular development?

2- Explore the roles of TGFβ / Actβa during tail regeneration.

It is known that TGFβ signalling is essential for regeneration but it is not clear which biological process (proliferation, differentiation, migration) is controlled this signalling pathway. Using tail regeneration in Xenopus, we will address this question and in particular test the hypothesis that Actβa is important for vascularisation during regeneration. We will also generate transgenic lines allowing us to monitor TGFβ signalling live during regeneration in order to establish where and when the signal is active.

Finally, the transcriptional targets of Actβa during development and regeneration will be determined using RNAseq or microarray experiments. This will help us establish the similarity and differences of Actβa’s role in these two processes.

Funding Notes

This project has a Band 2 fee. Details of our different fee bands can be found on our website (View Website). For information on how to apply for this project, please visit the Faculty of Biology, Medicine and Health Doctoral Academy website (View Website).

Informal enquiries may be made directly to the primary supervisor.

References

Jazwinska et al. (2007) Activin-βA signaling is required for zebrafish fin regeneration. Curr Biol 17, 1390-95

Ho and Whitman (2008) TGFβ signaling is required for multiple processes during Xenopus tail regeneration Dev Biol, 315 (1) 203-16

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