Symbolic Clustering of Large Datasets

Abstract

The proper function of the central nervous system requires the appropriate connections between glutamatergic neurons and GABAergic interneurons. Cortical GABAergic interneurons are characterized by extraordinary neurochemical and functional diversity. Impaired development and/or function of GABAergic interneurons can lead to severe neurodevelopmental disorders such as schizophrenia, epilepsy and autism. Recent studies have uncovered some of the molecular components underlying interneuron development, including the cellular and molecular mechanisms guiding their migration to the cortex, whereas the intracellular components involved are still unknown. Rac1, a member of the Rac subfamily of Rho GTPases, has been implicated in various cellular processes such as cell cycle dynamics, axonogenesis and migration. To address the specific role of Rac1 in interneuron progenitors originating in the medial ganglionic eminence, we have used Cre/ loxP technology. The ablation of Rac1 from mitotic progenitors, results in a delayed cell cycle exit, which in turn leads to a later onset of migration towards the cortex. As a consequence, only half of GABAergic interneurons are found in the postnatal cortex. Ablation of Rac1 from postmitotic progenitors does not result in similar defects, thus underlying a novel, cell autonomous and stagespecific requirement for Rac1 activity, within proliferating progenitors of cortical interneurons. Rac1 is necessary for their transition from G1 to S phase, at least in part by regulating CyclinD levels and Retinoblastoma protein phosphorylation.