T-ERC - Tremplin-ERC

Neural stem cells proliferation during normal and pathological brain development – NEURODEVO

Submission summary

Development of the neocortex occurs via proliferation of neural stem cells that generate all neocortical neurons.
The central goal of this project is to understand how proliferation of different pools of neural stem cells is controlled both
spatially and temporally to allow proper formation of the mammalian neocortex. We aim to understand how variations
in neural stem cell proliferation may account for the large expansion of the human brain, but also how alterations may
lead to pathological brain development.
In mice, the major neural stem cells are the apical Radial Glial (aRG) cells. These cells undergo cell cycledependent
nuclear oscillations to position their nucleus at the ventricular surface of the brain for mitosis. The mechanism
and role of this positional control of cell division, which also occurs in a wide variety of non-neuronal epithelia, is
currently unknown.
The remarkable expansion of the human neocortex is thought to partly arise from a second pool of neural stem
cells, called the basal Radial Glial (bRG) cells. Because of their extreme rarity in rodent models, the mechanisms
controlling proliferation and self-renewal of these neural stem cells remain largely unexplored.
With this project we will:
1. Determine the role of ventricular cell division in aRG cells.
Using in utero DNA electroporation, coupled to live imaging of embryonic brain slices, we will answer this long-standing
question.
2. Assess the involvement of bRG cells in human brain expansion and brain malformations.
By developing methods to image human and mouse bRG cells, we will determine how bRG cells migrate, divide and
whether defects in these cells can explain brain malformations in patients.
3. Identify and characterize novel mutated genes causing brain malformations in patients.
Using whole exome sequencing of a cohort of 40 patients with unexplained brain malformations, we will identify novel
mutated genes. We will then characterize the role of these genes for proper development of the neocortex.

Project coordinator

Monsieur Alexandre Baffet (INSTITUT CURIE - SECT DE RECHERCHE)

The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.

Partner

IC INSTITUT CURIE - SECT DE RECHERCHE

Help of the ANR 149,796 euros
Beginning and duration of the scientific project: December 2016 - 12 Months

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