The Purkinje neuron: A central orchestrator of cerebellar neurogenesis.

Abstract

Within the cyto-architecture of the brain is an often complex, but balanced, neuronal circuitry, the successful construction of which relies on the coordinated generation of functionally opposed neurons. Indeed, deregulated production of excitatory/inhibitory interneurons can greatly disrupt the integrity of excitatory/inhibitory neuronal transmission, which is a hallmark of neurodevelopmental disorders such as autism. Recent work has demonstrated that the Purkinje neuron, the central integrator of signaling within the cerebellar system, acts during development to ensure that neurogenesis occurring in spatially opposed domains reaches completion by transmitting the Sonic hedgehog ligand bi-directionally. In addition to a classic role in driving granule cell precursor proliferation, we now know that Purkinje neuron-derived Sonic hedgehog is simultaneously disseminated to the neonatal white matter. Within this neurogenic niche a lineage of Shh-responding stem and progenitor cells expand pools of GABAergic interneuron and astrocyte precursors. These recent findings advance our understanding of how Purkinje neurons function dynamically to oversee completion of a balanced cerebellar circuit.