(BBSRC NWD) Investigating the role of N-cadherin during hollowing neural tube morphogenesis The University of Manchester in United Kingdom

The neural tube is the precursor to the brain and spinal cord. Congenital neural tube defects are prevalent in humans (>1/1000 births). Designing prevention strategies is complicated by the many different mechanisms that must occur at a subcellular level to control this tissue-scale event. Adding to this complexity, the neural tube forms via different mechanisms along its length. For example, most of the human neural tube forms via folding a sheet of cells and subsequent inflation (primary neurulation). However, the base of the spinal neural tube forms via inflation of a fluid-filled cavity within an initially solid tissue, from the inside out (hollowing neurulation). To allow lumen inflation, neuroepithelial progenitor cells must first undergo a mesenchymal to epithelial transition within a solid tissue and align their apical-lateral junctions in the centre of the tissue. The force balance between cells must be coordinated over long distances, to ensure organised tissue structure and subsequent smooth lumen opening. We found that early cadherin protein upregulation in the middle of developing epithelial tubes is necessary and sufficient for the localisation of the apical membrane initiation site (AMIS) (Liang et al., 2022). However, it is not known how cadherin itself upregulated at the middle of organ primordia (Symonds and Buckley et al., 2020). Using an advanced in vivo optogenetic approach within the zebrafish hindbrain, we have also recently discovered that local changes in tissue stress are asymmetrically propagated long distances along the anterior-posterior axis via their lateral cadherin-based cell-cell adhesions (Crellin et al., 2024). However, the role of cadherin patterning in controlling local changes in tissue force balance is not well understood. Continuing to use the zebrafish hindbrain as a tractable model of hollowing neurulation, this project will use a combination of mosaic CRISPR-CAS9 and optogenetic approaches to test the role of N-cadherin based adhesions in the polarisation and morphogenesis of the hollowing neural tube. This work will use cutting edge optogenetic and quantitative approaches to further understanding of the important developmental process of hollowing neurogenesis.

https://research.manchester.ac.uk/en/persons/clare-buckley

https://research.manchester.ac.uk/en/persons/shane.herbert

https://research.manchester.ac.uk/en/persons/sarah.woolner

Eligibility

Applicants must have obtained or be about to obtain a minimum Upper Second class UK honours degree, or the equivalent qualifications gained outside the UK, in an appropriate area of science, engineering or technology.

International applicants

We are only able to offer a limited number of full studentships to applicants outside the UK. Therefore, full studentships will only be awarded to exceptional quality international candidates due to the competitive nature of this scheme.

International applicants must ensure they meet the academic eligibility criteria (including English language) before applying. Visit our ‘ Eligibility and entry requirements’ page to find out more about our English language requirements.

Before you Apply

Browse our BBSRC NWD in Bioscience projects and discover one you're passionate about that matches your interests, ambitions and goals.

Applicants must make direct contact with preferred supervisors before applying. It is your responsibility to make arrangements to meet with potential supervisors, prior to submitting a formal online application.

How to Apply

All applications should be made via our specific BBSRC NWDP in Bioscience online application form . This is a separate application process specifically for all candidates for this scheme. Applications should not be made through either university’s usual online application system.

You must submit your application form along with the required supporting documents by the deadline date. You can select up to two projects on one single application, noting the title of each project from the advert and the supervisor name. This can include two projects from one institution or a project from each institution.

Before you complete your application you should prepare the following supporting documents:

• CV
• Personal statement
• Degree certificates and transcripts (if your qualification is still pending, please ensure this is clear on your application form and you can send this to us at a later date)
• Two references
• Evidence of English language qualifications (if completed)

Complete the application form: https://forms.office.com/e/HVXALrVa0P

Once you have completed your application, you'll receive a confirmation email and you should reply to this email with all of your supporting documentation as soon as possible to: [email protected]

Deadline: Friday, 31 January 2025, 5pm

Late or incomplete applications will not be considered.

If you need help with this stage of the process, or have any queries regarding your eligibility (such as if you achieved unexpectedly low degree results due to extenuating circumstances), please contact the Doctoral Admissions team for advice at [email protected] .

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