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.
Highlights
The orderly development of embryonic tissues relies on gene regulatory networks that control patterns of gene expression, tissue growth, and cell differentiation [1,2]
The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
In ventral regions of the developing spinal cord, proliferating progenitors are exposed to a gradient of sonic hedgehog (Shh) signalling that controls the expression of a set of homeodomain and basic helix-loop-helix transcription factors (TFs) [3,4,5]
Summary
The orderly development of embryonic tissues relies on gene regulatory networks that control patterns of gene expression, tissue growth, and cell differentiation [1,2]. In ventral regions of the developing spinal cord, proliferating progenitors are exposed to a gradient of sonic hedgehog (Shh) signalling that controls the expression of a set of homeodomain and basic helix-loop-helix (bHLH) transcription factors (TFs) [3,4,5]. These TFs form a gene regulatory network that progressively allocates progenitor identity, dividing the spinal cord into molecularly discrete domains arrayed along the dorsal-ventral axis [6,7]. This combinatorial transcriptional code determines the subtype identity of the postmitotic neurons generated by progenitors in each domain, thereby controlling the position at which motor neurons (MNs) and interneurons emerge [3,8,9,10]
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