Benutzerspezifische Werkzeuge

A27: Signal receptors in the generation of subtype specific motor neuron progenitors

Project leader: Dr. A. Gavalas

 Neural stem cell (NSC) transplantations in animal models of motor neuron degenerative diseases show a therapeutic effect. Improvement of this therapeutic potential and application in disease modelling will depend on the identification of specific signalling molecules that promote specification, survival and maturation of distinct subtype motor neuron progenitors. Results from our lab suggest that timely inducible expression of specific Hox genes in mouse embryonic stem (ES) cell derived neural stem (NS) cells can generate cells of specific anteroposterior (AP) identities. These cells are responsive to shh signalling thus allowing the generation of distinct motorneuron progenitors (MNPs). Using this approach we are uncovering receptor tyrosine kinases (RTKs), Nuclear Receptors (NRs) and G protein coupled receptors (GPCRs) for the late steps of MN progenitor specification. Results suggest the existence of a receptor code for distinct MNPs.

Future work will elucidate the expression profiles of identified receptors in distinct MNPs. We will then use Hoxb1 inducible expression combined with shh signalling and signals specific for facial branchiomotor (fbm) neurons to generate such progenitors. These cells will be grafted in the facial motor nucleus of mice to assess their maturation, survival and axonal extension capacity. Combined ChIP and RNA Seq experiments will pinpoint genetic networks implicated in the specification of distinct MNP subtypes.

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Funding program:

DFG