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Control of spinal motor neuron terminal differentiation through sustained Hoxc8 gene activity

Catarina Catela, Yifei Weng, Kailong Wen, Weidong Feng, View ORCID ProfilePaschalis Kratsios
doi: https://doi.org/10.1101/2021.05.26.445841
Catarina Catela
1Department of Neurobiology, University of Chicago, Chicago, IL, USA
2University of Chicago Neuroscience Institute, Chicago, IL, USA
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Yifei Weng
1Department of Neurobiology, University of Chicago, Chicago, IL, USA
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Kailong Wen
1Department of Neurobiology, University of Chicago, Chicago, IL, USA
2University of Chicago Neuroscience Institute, Chicago, IL, USA
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Weidong Feng
1Department of Neurobiology, University of Chicago, Chicago, IL, USA
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Paschalis Kratsios
1Department of Neurobiology, University of Chicago, Chicago, IL, USA
2University of Chicago Neuroscience Institute, Chicago, IL, USA
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  • ORCID record for Paschalis Kratsios
  • For correspondence: pkratsios@uchicago.edu
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ABSTRACT

Spinal motor neurons (MNs) constitute cellular substrates for several movement disorders. Although their early development has received much attention, how spinal MNs become and remain terminally differentiated is poorly understood. Here, we determined the transcriptome of mouse brachial MNs at embryonic and postnatal stages. We found that genes encoding homeodomain (HOX, LIM) transcription factors (TFs), previously implicated in early MN development, continue to be expressed postnatally, suggesting later functions. To test this, we inactivated Hoxc8 at successive stages of MN development. We found that Hoxc8 is not only required to establish but also maintain expression of several MN terminal differentiation markers. Furthermore, we uncovered novel TFs with continuous MN expression, a Hoxc8 dependency for maintained expression of Iroquois (Irx) homeodomain TFs, and a new role for Irx2 in MN development. Our findings dovetail recent observations in C. elegans MNs, pointing toward an evolutionarily conserved role for Hox in neuronal terminal differentiation.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted May 27, 2021.
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Control of spinal motor neuron terminal differentiation through sustained Hoxc8 gene activity
Catarina Catela, Yifei Weng, Kailong Wen, Weidong Feng, Paschalis Kratsios
bioRxiv 2021.05.26.445841; doi: https://doi.org/10.1101/2021.05.26.445841
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Control of spinal motor neuron terminal differentiation through sustained Hoxc8 gene activity
Catarina Catela, Yifei Weng, Kailong Wen, Weidong Feng, Paschalis Kratsios
bioRxiv 2021.05.26.445841; doi: https://doi.org/10.1101/2021.05.26.445841

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