Building the vertebrate spine: the neck to thorax transition.

MUNSTERBERG_U23DTP

The segmentation of the body plan during embryogenesis is a fundamental and conserved feature of all vertebrate species. It results in the metameric organization of the vertebrae and the associated skeletal muscles, nerves, and blood vessels.

The vertebrate spine is generated by somites, transient blocks of cells that bud off from the unsegmented paraxial mesoderm (PSM) on each side of the neural tube.
In previous work, we have determined how gene expression is remodelled along the anterior-posterior axis of developing chick embryos to generate the different sections of the spine.

Using genome-wide methods, ATAC-seq and RNA-seq, we identified accessible chromatin and differentially expressed genes. We focused on the neck to thorax (C/T) transition, as the separation of the head from the forelimbs allowed its free movement and enabled adaptations. Thus, this region is of evolutionary importance. Furthermore congenital malformations of the spine, such as a cervical rib, are associated with thoracic outlet syndrome in human, which can lead to pressure on the brachial plexus and affect visceral organs or cause pain.

This project will validate several novel markers associated with C/T axial identity, such as regulatory elements, protein coding genes and lncRNAs, and investigate their function in vivo.

To examine the conservation of genetic mechanisms we will compare embryos of avian species with shorter or longer necks.

The project will provide training in experimental embryology, in vivo approaches and genome-wide molecular analysis of chromatin dynamics and gene expression.

A team of supervisors with complementary expertise will support the successful student candidate, who should be motivated and curious.

Scientific collaborations and conference attendance will provide training – in addition to opportunities offered by the DTP, UEA and the NRP.

References

– Smith, E.L., Mok, G.F. and Münsterberg, A.E., Investigating chromatin accessibility during development and differentiation by ATAC-sequencing to guide the identification of cis-regulatory elements. Biochem Soc Trans. 50(3), 1167-77, 2022, doi: 10.1042/BST20210834.

-Weldon, S.A. and Münsterberg, A.E., Somite development and regionalisation of the vertebral axial skeleton. Seminars in Cell & Developmental Biology, Volume 127, Pages 10-16, 2022, doi: 10.1016/j.semcdb.2021.10.003.

-Mok, G.F……and Münsterberg, A.E., Characterising open chromatin in chick embryos identifies cis- regulatory elements important for paraxial mesoderm formation and axis extension. Nature Comms, 2021. DOI 10.1038/s41467-021-21426-7

– Mok, G.F……and Münsterberg, A.E., miR-133-mediated regulation of the Hedgehog pathway orchestrates embryo myogenesis. Development, 2018. 145(12). DOI 10.1242/dev.159657