Imperial College London
Alternate

ProfessorVictorTybulewicz

Faculty of Medicine, Department of Immunology and Inflammation

Visiting Professor
 
 
 
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Contact

 

+44 (0)20 3796 1612v.tybulewicz Website CV

 
 
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Location

 

L2-2720Francis Crick InstituteThe Francis Crick Institute

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Summary

 

Publications

Citation

BibTex format

@article{Rayon:2020:10.1126/science.aba7667,
author = {Rayon, T and Stamataki, D and Perez-Carrasco, R and Garcia-Perez, L and Barrington, C and Melchionda, M and Exelby, K and Lazaro, J and Tybulewicz, VLJ and Fisher, EMC and Briscoe, J},
doi = {10.1126/science.aba7667},
journal = {Science},
pages = {1--15},
title = {Species-specific pace of development is associated with differences in protein stability},
url = {http://dx.doi.org/10.1126/science.aba7667},
volume = {369},
year = {2020}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - INTRODUCTIONWhat determines the pace of embryonic development? Although the molecular and cellular mechanisms of many developmental processes are evolutionarily conserved, the pace at which these operate varies considerably between species. The tempo of embryonic development controls the rate of individual differentiation processes and determines the overall duration of development. Despite its importance, however, the mechanisms that control developmental tempo remain elusive.RATIONALEComparing highly conserved and well-characterized developmental processes in different species permits a search for mechanisms that explain differences in tempo. The specification of neuronal subtype identity in the vertebrate spinal cord is a prominent example, lasting less than a day in zebrafish, 3 to 4 days in mouse, and around 2 weeks in human. The development of the spinal cord involves a well-defined gene regulatory program comprising a series of stereotypic changes in gene expression, regulated by extrinsic signaling as cells differentiate from neural progenitors to postmitotic neurons. The regulatory program and resulting neuronal cell types are highly similar in different vertebrates, despite the difference in tempo between species. We therefore set out to characterize the pace of differentiation of one specific neuronal subtype—motor neurons—in human and mouse and to identify molecular differences that explain differences in pace. To this end, we took advantage of the in vitro recapitulation of in vivo developmental programs using the directed differentiation of human and mouse embryonic stem cells.RESULTSWe found that all stages of the developmental progression from neural progenitor to motor neuron were proportionally prolonged in human compared with mouse, resulting in human motor neuron differentiation taking about 2.5 times longer than mouse. Differences in tempo were not due to differences in the sensitivity of cells to signals, nor could they be attribute
AU  - Rayon,T
AU  - Stamataki,D
AU  - Perez-Carrasco,R
AU  - Garcia-Perez,L
AU  - Barrington,C
AU  - Melchionda,M
AU  - Exelby,K
AU  - Lazaro,J
AU  - Tybulewicz,VLJ
AU  - Fisher,EMC
AU  - Briscoe,J
DO  - 10.1126/science.aba7667
EP  - 15
PY  - 2020///
SN  - 0036-8075
SP  - 1
TI  - Species-specific pace of development is associated with differences in protein stability
T2  - Science
UR  - http://dx.doi.org/10.1126/science.aba7667
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000573904400028&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - https://science.sciencemag.org/content/369/6510/eaba7667
VL  - 369
ER  -
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