Deconstructing cerebellar development cell by cell
Autoři:
Max J. van Essen aff001; Samuel Nayler aff001; Esther B. E. Becker aff001; John Jacob aff002
Působiště autorů:
Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United Kingdom
aff001; Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom
aff002
Vyšlo v časopise:
Deconstructing cerebellar development cell by cell. PLoS Genet 16(4): e32767. doi:10.1371/journal.pgen.1008630
Kategorie:
Review
doi:
https://doi.org/10.1371/journal.pgen.1008630
Souhrn
The cerebellum is a pivotal centre for the integration and processing of motor and sensory information. Its extended development into the postnatal period makes this structure vulnerable to a variety of pathologies, including neoplasia. These properties have prompted intensive investigations that reveal not only developmental mechanisms in common with other regions of the neuraxis but also unique strategies to generate neuronal diversity. How the phenotypically distinct cell types of the cerebellum emerge rests on understanding how gene expression differences arise in a spatially and temporally coordinated manner from initially homogeneous cell populations. Increasingly sophisticated fate mapping approaches, culminating in genetic-induced fate mapping, have furthered the understanding of lineage relationships between early- versus later-born cells. Tracing the developmental histories of cells in this way coupled with analysis of gene expression patterns has provided insight into the developmental genetic programmes that instruct cellular heterogeneity. A limitation to date has been the bulk analysis of cells, which blurs lineage relationships and obscures gene expression differences between cells that underpin the cellular taxonomy of the cerebellum. This review emphasises recent discoveries, focusing mainly on single-cell sequencing in mouse and parallel human studies that elucidate neural progenitor developmental trajectories with unprecedented resolution. Complementary functional studies of neural repair after cerebellar injury are challenging assumptions about the stability of postnatal cellular identities. The result is a wealth of new information about the developmental mechanisms that generate cerebellar neural diversity, with implications for human evolution.
Klíčová slova:
Cerebellum – Gene expression – Granule cells – Homeobox – Interneurons – Neurons – Purkinje cells – Transcription factors
Zdroje
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