Seminar

From mouse brain development to human congenital malformations

Dr. Xavier Miró

Proper area patterning of the neocortex is a crucial developmental event, because neocortical areas form the basis for sensory perception, control of our movements, and mediate our behavior. Many features must be properly specified during this process, from the determination of area's function and interaction with other neural structures, to the appropiate size. A disregulation of this process can lead to dramatic consequences, including lethality.

Defining the target genes that control arealization and determine how they function to generate area specializations is an important challenge. We have developed a large-scale screen using cDNA-microarrays to find new genes differentially expressed within the cortex and therefore might be involved in arealization. From them, a member of the epigenetic regulation has been highlighted, and the generation of deficient mice has resulted in a phenotype that overlaps with clinical manifestations of Chiari, a human congenital malformation with an unknown genetically origin up to now. Our work strongly suggests that brain malformations such as Chiari can result from altered epigenetic regulation of genes involved in cell proliferation in the brain.