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  4. Dynamic extrinsic pacing of the HOX clock in human axial progenitors controls motor neuron subtype specification
 
research article

Dynamic extrinsic pacing of the HOX clock in human axial progenitors controls motor neuron subtype specification

Mouilleau, Vincent
•
Vaslin, Célia
•
Gribaudo, Simona
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June 27, 2020
bioRxiv

Rostro-caudal patterning of vertebrates depends on the temporally progressive activation of HOX genes within axial stem cells that fuel axial embryo elongation. Whether HOX genes sequential activation, the “HOX clock”, is paced by intrinsic chromatin-based timing mechanisms or by temporal changes in extrinsic cues remains unclear. Here, we studied HOX clock pacing in human pluripotent stem cells differentiating into spinal cord motor neuron subtypes which are progenies of axial progenitors. We show that the progressive activation of caudal HOX genes in axial progenitors is controlled by a dynamic increase in FGF signaling. Blocking FGF pathway stalled induction of HOX genes, while precocious increase in FGF alone, or with GDF11 ligand, accelerated the HOX clock. Cells differentiated under accelerated HOX induction generated appropriate posterior motor neuron subtypes found along the human embryonic spinal cord. The HOX clock is thus dynamically paced by exposure parameters to secreted cues. Its manipulation by extrinsic factors alleviates temporal requirements to provide unprecedented synchronized access to human cells of multiple, defined, rostro-caudal identities for basic and translational applications.

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Type
research article
DOI
10.1101/2020.06.27.175646
Author(s)
Mouilleau, Vincent
Vaslin, Célia
Gribaudo, Simona
Robert, Rémi
Nicolas, Nour
Jarrige, Margot
Terray, Angélique
Lesueur, Léa
Mathis, Mackenzie W.  
Croft, Gist
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Date Issued

2020-06-27

Published in
bioRxiv
Article Number

175646

Editorial or Peer reviewed

REVIEWED

Written at

OTHER

EPFL units
UPMWMATHIS  
Available on Infoscience
November 6, 2020
Use this identifier to reference this record
https://infoscience.epfl.ch/handle/20.500.14299/173023
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