NeuroDev

Brain development is associated with a series of developmental sequences including the proliferation, migration and differentiation of neurons and glial cells. In humans, it is a particularly long process starting in early embryonic life and lasting up to the end of adolescence.

These sequences of events are not fully programmed but rely on developmental checkpoints. Altering these sequences through genetic mutations or environmental insults leads to phenotypic alterations and lifelong neurological and psychiatric disorders, termed Neurodevelopmental Disorders (NDDs). Later in the lifespan, neurodegenerative diseases could also result from perturbations in late developmental sequences and/or the impairment of brain maintenance.

The complexity of human brain development renders human monogenic genetic disorders unique models to decipher the key mechanisms involved. Our work focuses on inherited NDDs affecting:

• antenatal or postnatal brain growth (microcephalies),
• white matter development (leukodystrophies),
• rare neuronal disorders characterized by a pubertal defect.

Our objective is to approach neuronal and glial cell dysfunctions in NDDs from a unique integrative viewpoint using five complementary approaches centered on in vivo and cellular NDD models and their therapy:

(1) deciphering the role of energy pathways in the fate of neural progenitors,
(2) understanding the role of centrosome and Golgi apparatus defects in brain cell division and maturation,
(3) analyzing the link between membrane trafficking defects and postnatal neuroendocrine maturation,
(4) studying mitochondrial dysfunction in appropriate mouse models of NDDs, in order to design original therapies,
(5) developing integrative genomic diagnostic tools for the identification of common pathways involved in NDDs that are suitable for therapeutic targeting.