Research Article

Spatiotemporal expansion of primary progenitor zones in the developing human cerebellum

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Science  25 Oct 2019:
Vol. 366, Issue 6464, pp. 454-460
DOI: 10.1126/science.aax7526

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Close-up of human cerebellar development

Early on, cerebellar development shares similarities across humans, nonhuman primates, and even mice. But differences emerge while development progresses, as cellular and molecular analyses by Haldipur et al. now reveal. The rhombic lip persists longer during cerebellar development in humans than in either the mouse or the macaque and generates a pool of neuroprogenitor cells. Similarly, the ventricular zone of the human cerebellum goes a step further than that of the mouse in developing an additional proliferative layer with outer radial glia cells. Transcriptome analysis revealed detailed similarities and differences between progenitor cells of the developing human cerebellum and neocortex.

Science, this issue p. 454

Abstract

We present histological and molecular analyses of the developing human cerebellum from 30 days after conception to 9 months after birth. Differences in developmental patterns between humans and mice include spatiotemporal expansion of both ventricular and rhombic lip primary progenitor zones to include subventricular zones containing basal progenitors. The human rhombic lip persists longer through cerebellar development than in the mouse and undergoes morphological changes to form a progenitor pool in the posterior lobule, which is not seen in other organisms, not even in the nonhuman primate the macaque. Disruptions in human rhombic lip development are associated with posterior cerebellar vermis hypoplasia and Dandy-Walker malformation. The presence of these species-specific neural progenitor populations refines our insight into human cerebellar developmental disorders.

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