Cookies disclaimer

I agree Our site saves small pieces of text information (cookies) on your device in order to deliver better content and for statistical purposes. You can disable the usage of cookies by changing the settings of your browser. By browsing our website without changing the browser settings you grant us permission to store that information on your device.

Olig2 and the regulation of neural stem cell fate. (360G-Wellcome-092844_Z_10_A)

During development of the central nervous system (CNS), neuroepithelial stem cells (NSCs), residing in the ventricular zones (VZ) of the embryonic brain and spinal cord, divide and differentiate to generate all the neurons and glial cells (astrocytes and oligodendrocytes) of the mature CNS. Typically, neurons form before glia. In the ventral spinal cord, for example, embryonic NSCs of the pMN progenitor domain generate several subtypes of motor neurons (MNs) before switching abruptly (at E12.5 in mouse) to production of oligodendrocyte precursors (OLPs). The OLPs then migrate away from the VZ into all parts of the spinal cord before associating with axons, differentiating into post-mitotic oligodendrocytes (OLs) and synthesizing myelin. We aim to address how NSCs switch at a predetermined time from neuron to glial production ? specifically, the mechanism of the MN-OLP fate switch in the ventral spinal cord. Broadly, the proposed project aims to characterize the role and regulation of the basic helix-loophelix transcription factor Olig2 in the MN-OLP fate-switch. Recent work from the Richardson lab showed that a specific serine residue (S147) in Olig2 is phosphorylated during MN specification and de-phosphorylated at the switch to OLP production. What triggers de-phosphorylation of Olig2 at the time of the MN-OLP switch? The sequence surrounding S147 conforms to a protein kinase-A target site, but the identity of the putative phosphatase responsible for dephosphorylation has not been established. What are the targets and co-factors of Olig2 in its different phosphorylated states that coordinate the temporally-defined switch in NSC fate? And what are the functions of the other predicted Olig2 phosphorylation states? This project will involve three distinct lines of investigation. 1: Characterizing the expression of candidate phosphatases/phosphatase inhibitors in the ventral spinal cord at the time of the MNOLP fate-switch. 2: Identifying target genes of Olig2 in its phosphorylated and de-phosphorylated states. 3: Characterizing the developmental function of another Olig2 phosphorylation site, S263, a potential target of p38 mitogen-activated protein kinase (MAPK).


27 Jan 2012

Grant details
Amount Awarded 31882
Applicant Surname Sinclair-Wilson
Approval Committee PhD Studentships
Award Date 2012-01-27T00:00:00+00:00
Financial Year 2011/12
Grant Programme: Title PhD Studentship (Basic)
Internal ID 092844/Z/10/A
Lead Applicant Mr Alexander Sinclair-Wilson
Planned Dates: End Date 2014-09-30T00:00:00+00:00
Planned Dates: Start Date 2011-10-01T00:00:00+00:00
Recipient Org: Country United Kingdom
Region Greater London
Sponsor(s) Prof Claudio Stern
Additional data added by GrantNav