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Migration and integration of GABAergic interneurons into the developing cerebral cortex: a transgenic approach

Objective

Inhibitory interneurons function as modulators of local circuit excitability. Their properties are of fundamental importance for normal brain function therefore understanding how these cells are generated during development may provide insight into neurodevelopmental disorders such as epilepsy and schizophrenia, in which interneuron defects have been implicated. Inhibitory GABAergic interneurons of the cerebral cortex (pallium) are generated from proliferating subpallial precursors during development and migrate extensively to populate the cortex. The aim of this proposal is to identify genetic pathways and signalling systems that underlie cortical interneuron migration and integration into functional neuronal circuits. Distinct interneuron subtypes are generated from the two most prominent neuroepithelial stem cell pools in the subpallium: the medial ganglionic eminence (MGE) and the lateral/caudal ganglionic eminence (LGE/CGE). We will genetically tag and purify interneurons originating from these precursors in order to examine their transcriptomes and identify factors involved in specification and migration. We will use Cre-lox fate mapping in transgenic mice to label specific sub-populations of neural stem cells and their differentiated progeny in the embryonic telencephalon. This will allow us to determine whether subdomains of the MGE or LGE/CGE neuroepithelium generate interneurons with distinct neurochemical phenotypes and/or characteristic migratory properties. Electrical activity and/or neurotransmitter receptor activation can act in concert with genetic programs to promote precursor proliferation, neuronal differentiation as well as neuronal migration. We will use gain-of-function and loss-of-function approaches to examine the role of neurotransmitters and neuropeptides at early stages of interneuron migration to the cortex.

Field of science

  • /medical and health sciences/medical biotechnology/cells technologies/stem cells
  • /medical and health sciences/basic medicine/neurology/epilepsy
  • /medical and health sciences/clinical medicine/psychiatry/schizophrenia
  • /social sciences/sociology/social problems/migration

Call for proposal

ERC-2007-StG
See other projects for this call

Funding Scheme

ERC-SG - ERC Starting Grant

Host institution

UCL Elizabeth Garrett Anderson Institute for Women’s Health
Address
Gower Street
WC1E 6BT London
United Kingdom
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 1 250 000
Principal investigator
Nicoletta Kessaris (Name On Phd Certificate: Tekki) (Dr.)
Administrative Contact
Michael Browne (Mr.)

Beneficiaries (1)

UCL Elizabeth Garrett Anderson Institute for Women’s Health
United Kingdom
EU contribution
€ 1 250 000
Address
Gower Street
WC1E 6BT London
Activity type
Higher or Secondary Education Establishments
Principal investigator
Nicoletta Kessaris (Name On Phd Certificate: Tekki) (Dr.)
Administrative Contact
Michael Browne (Mr.)