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Hes1 expression is reduced in Tbx1 null cells and is required for the development of structures affected in 22q11 deletion syndrome

22q11 deletion syndrome (22q11DS) is characterised by aberrant development of the pharyngeal apparatus and the heart with haploinsufficiency of the transcription factor TBX1 being considered the major underlying cause of the disease. Tbx1 mutations in mouse phenocopy the disorder. In order to identi...

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Autores principales: van Bueren, Kelly Lammerts, Papangeli, Irinna, Rochais, Francesca, Pearce, Kerra, Roberts, Catherine, Calmont, Amelie, Szumska, Dorota, Kelly, Robert G., Bhattacharya, Shoumo, Scambler, Peter J.
Formato: Texto
Lenguaje:English
Publicado: Elsevier 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2877781/
https://www.ncbi.nlm.nih.gov/pubmed/20122914
http://dx.doi.org/10.1016/j.ydbio.2010.01.020
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author van Bueren, Kelly Lammerts
Papangeli, Irinna
Rochais, Francesca
Pearce, Kerra
Roberts, Catherine
Calmont, Amelie
Szumska, Dorota
Kelly, Robert G.
Bhattacharya, Shoumo
Scambler, Peter J.
author_facet van Bueren, Kelly Lammerts
Papangeli, Irinna
Rochais, Francesca
Pearce, Kerra
Roberts, Catherine
Calmont, Amelie
Szumska, Dorota
Kelly, Robert G.
Bhattacharya, Shoumo
Scambler, Peter J.
author_sort van Bueren, Kelly Lammerts
collection PubMed
description 22q11 deletion syndrome (22q11DS) is characterised by aberrant development of the pharyngeal apparatus and the heart with haploinsufficiency of the transcription factor TBX1 being considered the major underlying cause of the disease. Tbx1 mutations in mouse phenocopy the disorder. In order to identify the transcriptional dysregulation in Tbx1-expressing lineages we optimised fluorescent-activated cell sorting of β-galactosidase expressing cells (FACS-Gal) to compare the expression profile of Df1/Tbx1(lacZ) (effectively Tbx1 null) and Tbx1 heterozygous cells isolated from mouse embryos. Hes1, a major effector of Notch signalling, was identified as downregulated in Tbx1(−)(/)(−) mutants. Hes1 mutant mice exhibited a partially penetrant range of 22q11DS-like defects including pharyngeal arch artery (PAA), outflow tract, craniofacial and thymic abnormalities. Similar to Tbx1 mice, conditional mutagenesis revealed that Hes1 expression in embryonic pharyngeal ectoderm contributes to thymus and pharyngeal arch artery development. These results suggest that Hes1 acts downstream of Tbx1 in the morphogenesis of pharyngeal-derived structures.
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spelling pubmed-28777812010-06-21 Hes1 expression is reduced in Tbx1 null cells and is required for the development of structures affected in 22q11 deletion syndrome van Bueren, Kelly Lammerts Papangeli, Irinna Rochais, Francesca Pearce, Kerra Roberts, Catherine Calmont, Amelie Szumska, Dorota Kelly, Robert G. Bhattacharya, Shoumo Scambler, Peter J. Dev Biol Article 22q11 deletion syndrome (22q11DS) is characterised by aberrant development of the pharyngeal apparatus and the heart with haploinsufficiency of the transcription factor TBX1 being considered the major underlying cause of the disease. Tbx1 mutations in mouse phenocopy the disorder. In order to identify the transcriptional dysregulation in Tbx1-expressing lineages we optimised fluorescent-activated cell sorting of β-galactosidase expressing cells (FACS-Gal) to compare the expression profile of Df1/Tbx1(lacZ) (effectively Tbx1 null) and Tbx1 heterozygous cells isolated from mouse embryos. Hes1, a major effector of Notch signalling, was identified as downregulated in Tbx1(−)(/)(−) mutants. Hes1 mutant mice exhibited a partially penetrant range of 22q11DS-like defects including pharyngeal arch artery (PAA), outflow tract, craniofacial and thymic abnormalities. Similar to Tbx1 mice, conditional mutagenesis revealed that Hes1 expression in embryonic pharyngeal ectoderm contributes to thymus and pharyngeal arch artery development. These results suggest that Hes1 acts downstream of Tbx1 in the morphogenesis of pharyngeal-derived structures. Elsevier 2010-04-15 /pmc/articles/PMC2877781/ /pubmed/20122914 http://dx.doi.org/10.1016/j.ydbio.2010.01.020 Text en © 2010 Elsevier Inc. https://creativecommons.org/licenses/by-nc-nd/3.0/ Open Access under CC BY-NC-ND 3.0 (https://creativecommons.org/licenses/by-nc-nd/3.0/) license
spellingShingle Article
van Bueren, Kelly Lammerts
Papangeli, Irinna
Rochais, Francesca
Pearce, Kerra
Roberts, Catherine
Calmont, Amelie
Szumska, Dorota
Kelly, Robert G.
Bhattacharya, Shoumo
Scambler, Peter J.
Hes1 expression is reduced in Tbx1 null cells and is required for the development of structures affected in 22q11 deletion syndrome
title Hes1 expression is reduced in Tbx1 null cells and is required for the development of structures affected in 22q11 deletion syndrome
title_full Hes1 expression is reduced in Tbx1 null cells and is required for the development of structures affected in 22q11 deletion syndrome
title_fullStr Hes1 expression is reduced in Tbx1 null cells and is required for the development of structures affected in 22q11 deletion syndrome
title_full_unstemmed Hes1 expression is reduced in Tbx1 null cells and is required for the development of structures affected in 22q11 deletion syndrome
title_short Hes1 expression is reduced in Tbx1 null cells and is required for the development of structures affected in 22q11 deletion syndrome
title_sort hes1 expression is reduced in tbx1 null cells and is required for the development of structures affected in 22q11 deletion syndrome
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2877781/
https://www.ncbi.nlm.nih.gov/pubmed/20122914
http://dx.doi.org/10.1016/j.ydbio.2010.01.020
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