Signalling pathways that mediate the dual origins of the dorsal aorta

(MUNSTERBERG_U25DTP)

Embryo development is a fascinating process generating a highly organised body plan with many features that are conserved across different vertebrate species. This includes the metameric organization of the vertebrae and the associated skeletal muscles, nerves and blood vessels, produced by somites residing on each side of the neural tube. In previous work, we have determined molecular profiles of somites and adjacent tissues along the anterior-posterior axis of developing chick embryos. This identified accessible chromatin, differentially expressed genes and cis-regulatory elements (CRE) active in specific cell lineages. This project will investigate the functions of candidate genes arising from these data sets. Specifically, the student will investigate signalling interactions between somites and the lateral plate mesoderm (LPM), focussing on Wnt, FGF and BMP pathways. Signalling cross-talk between somite and LPM is important for the formation of the dorsal aorta, a bilateral primary vessel, which will fuse and later form major arteries in the head, neck and trunk. Furthermore, the dosal aorta is the source of hematopoietic stem cells within the organism, thus, its formation is of fundamental importance. Insights gained have potential relevance for regenerative medicine and tissue engineering. The project will use in vivo approaches for gene function analysis, genome editing and microscopy including live imaging and thus provide training in experimental embryology. An experienced team of supervisors will support the successful student candidate, who should be motivated and curious. Scientific collaborations, conference attendance and outreach activities will provide further training – in addition to opportunities offered by the DTP, UEA and the NRP.

 

References

Mok, G.F., et al., Characterising open chromatin in chick embryos identifies cis-regulatory elements important for paraxial mesoderm formation and axis extension. Nat Commun, 2021. 12(1): p. 1157

Mok, G.F., et al., Single cell RNA-sequencing and RNA-tomography of the avian embryo extending body axis. Front Cell Dev Biol, 2024. 12: p. 1382960

Song, J., et al., Smad1 transcription factor integrates BMP2 and Wnt3a signals in migrating cardiac progenitor cells. Proc Natl Acad Sci U S A, 2014. 111(20): p. 7337-42

McColl, J., et al., 4D imaging reveals stage dependent random and directed cell motion during somite morphogenesis. Sci Rep, 2018. 8(1): p. 12644