EASTBIO Examining the embryonic development of adult neural stem cells in the mammalian dentate gyrus.

Supervisors:

Dr Daniel Berg (University of Aberdeen)
https://www.abdn.ac.uk/people/daniel.berg

Dr Eunchai Kang (University of Aberdeen)
https://www.abdn.ac.uk/people/eunchai.kang

Professor Lynda Erskine (University of Aberdeen)
www.abdn.ac.uk/ims/research/profiles/l.erskine

New neurons are continually generated in discreet locations of the adult mammalian brain in a process called adult neurogenesis. One of these locations is the dentate gyrus (DG) of the hippocampus, where resident neural stem cells (NSCs) have the potential to divide and generate new neurons throughout life. The neurons generated in the adult DG integrate into the neural circuitry and play important roles in normal brain functions such as learning and memory. Additionally, aberrant neurogenesis in the DG has been implicated with epilepsy, depression, Alzheimer’s disease and schizophrenia. The NSCs in the DG have a radial-like morphology and express stem cell markers such Nestin and Sox2. Although many studies have examined the molecular signals that regulate the NSCs in the adult brain, little is known about how these NSCs are generated during development. In our previous work, we identified the precursor cells in the embryonic brain that generate the NSCs in the adult DG. We also developed techniques to lineage-trace these precursors and identified novel NSC markers using RNA-sequencing (Berg et al, Cell 2019). The aim of this project is to examine how adult NSCs and the adult neurogenic niche are generated during development and maintained in adults by investigating the role of NSC markers using DG ontogenesis as a model system. This will be done with the aim to develop techniques with which to manipulate endogenous NSCs for treatments of neurodevelopmental disorders and regeneration of the adult nervous system.

Objective 1) To investigate the role of novel NSCs markers in the generation and cellular behaviour of DG NSCs during development.

Objective 2) To identify key signalling pathways determining the generation and cellular behaviours of NSCs using transcriptomic analysis.

The student who will work on this project will learn techniques such as fate-mapping using immunohistochemistry, in-vivo genetic manipulation by in-utero electroporation and transcriptomic analysis using single cell RNA-sequencing. The student will also obtain fundamental concepts in the field of stem cell biology, brain development and adult neurogenesis. The ideal candidate should have some experience with cell and molecular biology and motivation to continue to develop these skills.

Application Procedure:

http://www.eastscotbiodtp.ac.uk/how-apply-0

Please send your completed EASTBIO application form, along with academic transcripts to Alison McLeod at [Email Address Removed]. Two references should be provided by the deadline using the EASTBIO reference form. Please advise your referees to return the reference form to [Email Address Removed].