MRC National Institute for Medical Research, London
Science for Health
François Guillemot group project:
Using stem cells for neuronal repair
In mammals, including humans, most neurons are generated during embryogenesis or soon after birth. During adulthood, neurons are produced in only two regions of the telencephalon, the dentate gyrus of the hippocampus and the subependymal zone lining the lateral ventricles, while in other brain regions, progenitor cells are restricted to the generation of glia cells. Even following stroke or in patients afflicted by neurodegenerative diseases, lost neurons are usually not replaced.
We study the regulation of adult neurogenesis in the dentate gyrus and subependymal zone in order to identify mechanisms that control the specification, proliferation, differentiation and migration of adult neuronal progenitors. For example, we have recently shown that the proneural protein Mash1 is essential for the self-renewal of stem cells and the generation of transit amplifying progenitors in the adult dentate gyrus and subependymal zone (unpublished data). Characterizing the pathways that control the normal development of adult neurogenic lineages will help design experimental approaches to promote neuronal replacement in injured brains.
We are also interested in characterizing the downstream mechanisms by which the proneural proteins Ngn2 and Mash1 specify the identity of glutamatergic cortical neurons and GABAergic basal ganglia neurons, respectively. These different types of neurons are affected in neuropathologies such as Alzheimer’s disease, Huntington’s disease or Schizophrenia. Characterizing the pathways that promote their generation from stem cells will help devise therapies to specifically replace the neuronal types that are lost in diseased brains.
Expression of proneural transcription factors
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Expression of proneural transcription factors in neural stem cell culture activates neurogenesis
Progenitor cells expressing proneural proteins
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Progenitor cells expressing proneural proteins generate new neurons in the adult dentate gyrus
Selected publications
- Galichet, C; Guillemot, F and Parras, CM (2008)
Neurogenin 2 has an essential role in development of the dentate gyrus.
Development 135, 2031-2041 PubMed abstract - Ozen, I; Galichet, C; Watts, C; Parras, C; Guillemot, F and Raineteau, O (2007)
Proliferating neuronal progenitors in the postnatal hippocampus transiently express the proneural gene Ngn2
European Journal of Neuroscience 25, 2591-2603 PubMed abstract - Berninger, B; Guillemot, F and Götz, M (2007)
Directing neurotransmitter identity of neurones derived from expanded adult neural stem cells
European Journal of Neuroscience 25, 2581-2590 PubMed abstract - Parras, CM; Galli, R; Britz, O; Soares, S; Galichet, C; Battiste, J; Johnson, JE; Nakafuku, M; Vescovi, A and Guillemot, F (2004)
Mash1 specifies neurons and oligodendrocytes in the postnatal brain.
EMBO Journal 23, 4495-4505 PubMed abstract
Guillemot group
Recent publications
Research projects
- Elucidating the genetic programmes for neurogenesis and gliogenesis
- Regulating gene expression in neural progenitors
- Using stem cells for neuronal repair
Guillemot biography
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