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{Redhead:2022:10.1101/2022.06.27.497841,
author = {Redhead, Y and Gibbins, D and Lana-Elola, E and Watson-Scales, S and Dobson, L and Krause, M and Liu, KJ and Fisher, EMC and Green, JBA and Tybulewicz, VLJ},
doi = {10.1101/2022.06.27.497841},
title = {Craniofacial dysmorphology in Down Syndrome is caused by increased dosage of Dyrk1a and at least three other genes},
url = {http://dx.doi.org/10.1101/2022.06.27.497841},
year = {2022}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - <jats:title>Abstract</jats:title><jats:p>Down syndrome (DS), trisomy of human chromosome 21 (Hsa21), occurs in 1 in 800 live births and is the most common human aneuploidy. DS results in multiple phenotypes, including craniofacial dysmorphology, characterised by midfacial hypoplasia, brachycephaly and micrognathia. The genetic and developmental causes of this are poorly understood. Using morphometric analysis of the Dp1Tyb mouse model of DS and an associated genetic mouse genetic mapping panel, we demonstrate that four Hsa21-orthologous regions of mouse chromosome 16 contain dosage-sensitive genes that cause the DS craniofacial phenotype, and identify one of these causative genes as <jats:italic>Dyrk1a</jats:italic>. We show that the earliest and most severe defects in Dp1Tyb skulls are in bones of neural crest (NC) origin, and that mineralisation of the Dp1Tyb skull base synchondroses is aberrant. Furthermore, we show that increased dosage of <jats:italic>Dyrk1a</jats:italic> results in decreased NC cell proliferation and a decrease in size and cellularity of the NC-derived frontal bone primordia. Thus, DS craniofacial dysmorphology is caused by increased dosage of <jats:italic>Dyrk1a</jats:italic> and at least three other genes.</jats:p><jats:sec><jats:title>Summary statement</jats:title><jats:p>Craniofacial dysmorphology in mouse models of Down syndrome is caused by increased dosage of at least four genes including <jats:italic>Dyrk1a</jats:italic>, resulting in reduced proliferation of neural crest-derived cranial bone progenitors.</jats:p></jats:sec>
AU  - Redhead,Y
AU  - Gibbins,D
AU  - Lana-Elola,E
AU  - Watson-Scales,S
AU  - Dobson,L
AU  - Krause,M
AU  - Liu,KJ
AU  - Fisher,EMC
AU  - Green,JBA
AU  - Tybulewicz,VLJ
DO  - 10.1101/2022.06.27.497841
PY  - 2022///
TI  - Craniofacial dysmorphology in Down Syndrome is caused by increased dosage of Dyrk1a and at least three other genes
UR  - http://dx.doi.org/10.1101/2022.06.27.497841
ER  -
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