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PLoS Biol. 2018 Feb 1;16(2):e2003127. doi: 10.1371/journal.pbio.2003127. eCollection 2018 Feb.

Olig2 and Hes regulatory dynamics during motor neuron differentiation revealed by single cell transcriptomics.

Author information

1
The Francis Crick Institute, London, United Kingdom.
2
Department of Neurobiology, Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, David Geffen School of Medicine at UCLA, University of California, Los Angeles, Los Angeles, California, United States of America.
3
Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, Michigan, United States of America.

Abstract

During tissue development, multipotent progenitors differentiate into specific cell types in characteristic spatial and temporal patterns. We addressed the mechanism linking progenitor identity and differentiation rate in the neural tube, where motor neuron (MN) progenitors differentiate more rapidly than other progenitors. Using single cell transcriptomics, we defined the transcriptional changes associated with the transition of neural progenitors into MNs. Reconstruction of gene expression dynamics from these data indicate a pivotal role for the MN determinant Olig2 just prior to MN differentiation. Olig2 represses expression of the Notch signaling pathway effectors Hes1 and Hes5. Olig2 repression of Hes5 appears to be direct, via a conserved regulatory element within the Hes5 locus that restricts expression from MN progenitors. These findings reveal a tight coupling between the regulatory networks that control patterning and neuronal differentiation and demonstrate how Olig2 acts as the developmental pacemaker coordinating the spatial and temporal pattern of MN generation.

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