Genetics and Development of the Cerebral Cortex

Cognitive functions occur primarily in the cerebral cortex and our intellectual ability is what distinguishes us most from ancestral vertebrates including other mammals.

Our aim is to understand the molecular mechanisms that control cell diversity and positioning in the developing cerebral cortex.

The cerebral cortex constitutes the dorsal part of the telencephalon, the most anterior territory of the brain. It has a laminar organization and is regionalized in distinct areas that serve different motor, sensory and cognitive functions. The formation of such a highly complex structure relies on the exquisite orchestration of the spatio-temporal generation of distinct cell types and the control of their migration and final settling position. Growing evidence supports the notion that the aetiology of many neurological and psychiatric illnesses, ranging from epilepsy to mental retardation, is to be found in the alteration of the developmental processes.

Events taking place in progenitor cells at early stages of development are crucial for the accurate construction of complex neural circuits. The Dbx1 homeodomain transcription factor is expressed in discrete subpopulations of progenitors, among which are those generated at the boundary between the developing cerebral cortex, dorsally, and the basal ganglia, ventrally. This boundary (the pallial-subpallial boundary) (PSB) may play a crucial role in the evolution of the cerebral cortex in mammals. Dbx1-derived cells are highly motile and their life span is short.

We have developed new molecular approaches to study cell fate allocation and function at the dorso-ventral boundary in the central nervous system. We are using a genetic approach in mouse that allows us to trace neuronal populations from their site of origin in progenitors to adulthood and to conditionally ablate them to study their role during development and postnatal life. We combine genomics and gene profile analysis using microarrays with classical embryology techniques, such as transplants in vivo and in vitro, electroporation in ovo and in utero, and behavioural tests.
These studies should provide a fuller understanding of the molecular control of cell diversity and lamination in the cerebral cortex and of the evolution of the neocortex in mammals. In addition, the conditional cell ablation system which we have developed in mice will allow us to engineer developmental models of cortical neuron deficiency and to improve our understanding and diagnosis of human cortical developmental disorders.

Our research is funded by national and international grants from the French Ministry of Education and Research, National Agency for Research (ANR), European Commission (STREP), “Fondation de la Recherche Medicale” (FRM), The City of Paris.
 

Selection of Publications

Teissier A., Griveau A., Vigier L., Piolot T., Borello U. and Pierani A. (2010) A novel transient glutamatergic population migrating from the pallial-subpallial boundary contributes to neocortical development. Journal Neuroscience, 30, 10563-10574.
Abstract

Griveau A., Borello U.^#, Causeret F.^#, Tissir F., Boggetto N., Karaz S. and Pierani A. (2010) A Novel Role for Dbx1-derived Cajal-Retzius Cells in Early Regionalization of the Cerebral Cortical Neuroepithelium. PLoS Biol., 8(7), e1000440.
Free Full Text

Borello U. and Pierani A. (2010) Patterning the cerebral cortex: travelling with morphogens. Current Opinion in Genetics and Development, 20, 408–415.
Abstract

Bielle F., Griveau A., Narboux-Nême N.,Vigneau S., Sigrist M., Arber S., Wassef  M. and Pierani A. (2005) Multiple origins of Cajal-Retzius cells at the borders in of the developing pallium. Nature Neuroscience, 8, 1002-1012.
abstract

Pierani A., Moran Rivard, L., Sunshine, M. J., Littman, D. R., Goulding, M., and Jessell T. M. (2001) Control of interneuron fate in the developing spinal cord by the progenitor homeodomain protein Dbx1. Neuron, 29, 367-384.
abstract

Last modified 11/ 2/2011

Top