Cerebellar nuclei neurons dictate cortical growth through developmental scaling of presynaptic Purkinje cells

Efficient function of neural systems requires the production of specific cell types in the correct proportions. Here we report that reduction of the earliest born neurons of the cerebellum, excitatory cerebellar nuclei neurons (eCN), results in a subsequent reduction in growth of the cerebellar cortex due to an accompanying loss of their presynaptic target Purkinje cells. Conditional knockout of the homeobox genes En1 and En2 ( En1/2 ) in the rhombic lip-derived eCN and granule cell precursors leads to embryonic loss of a subset of medial eCN and cell non-autonomous and location specific loss of Purkinje cells, with subsequent proportional scaling down of cortex growth. We propose that subsets of eCN dictate the survival of their specific Purkinje cell partners, and in turn sonic hedgehog secreted by Purkinje cells scales the expansion of granule cells and interneurons to produce functional local circuits and the proper folded morphology of the cerebellum.