Hes1 Expression is Reduced in Tbx1 Null Cells and is Required for the Development of Structures Affected in 22q11 Deletion Syndrome

Overview

Journal Dev Biol

Publisher Elsevier

Specialties Biology
Reproductive Medicine

Date 2010 Feb 4

PMID 20122914

Citations 32

Authors

Kelly Lammerts van Bueren

Irinna Papangeli

Francesca Rochais

Kerra Pearce

Catherine Roberts

Amelie Calmont

Dorota Szumska

Robert G Kelly

Shoumo Bhattacharya

Peter J Scambler

Affiliations

Soon will be listed here.

Abstract

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 beta-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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References

Kokubo H, Miyagawa-Tomita S, Nakazawa M, Saga Y, Johnson R . Mouse hesr1 and hesr2 genes are redundantly required to mediate Notch signaling in the developing cardiovascular system. Dev Biol. 2005; 278(2):301-9. DOI: 10.1016/j.ydbio.2004.10.025. View

High F, Zhang M, Proweller A, Tu L, Parmacek M, Pear W . An essential role for Notch in neural crest during cardiovascular development and smooth muscle differentiation. J Clin Invest. 2007; 117(2):353-63. PMC: 1783803. DOI: 10.1172/JCI30070. View

Kokubo H, Miyagawa-Tomita S, Tomimatsu H, Nakashima Y, Nakazawa M, Saga Y . Targeted disruption of hesr2 results in atrioventricular valve anomalies that lead to heart dysfunction. Circ Res. 2004; 95(5):540-7. DOI: 10.1161/01.RES.0000141136.85194.f0. View

Rutenberg J, Fischer A, Jia H, Gessler M, Zhong T, Mercola M . Developmental patterning of the cardiac atrioventricular canal by Notch and Hairy-related transcription factors. Development. 2006; 133(21):4381-90. PMC: 3619037. DOI: 10.1242/dev.02607. View

High F, Epstein J . The multifaceted role of Notch in cardiac development and disease. Nat Rev Genet. 2007; 9(1):49-61. DOI: 10.1038/nrg2279. View

Peirson S, Butler J, Foster R . Experimental validation of novel and conventional approaches to quantitative real-time PCR data analysis. Nucleic Acids Res. 2003; 31(14):e73. PMC: 167648. DOI: 10.1093/nar/gng073. View

Taddei I, Morishima M, Huynh T, Lindsay E . Genetic factors are major determinants of phenotypic variability in a mouse model of the DiGeorge/del22q11 syndromes. Proc Natl Acad Sci U S A. 2001; 98(20):11428-31. PMC: 58746. DOI: 10.1073/pnas.201127298. View

Oda T, Elkahloun A, Pike B, Okajima K, Krantz I, Genin A . Mutations in the human Jagged1 gene are responsible for Alagille syndrome. Nat Genet. 1997; 16(3):235-42. DOI: 10.1038/ng0797-235. View

Lindsay E, Vitelli F, Su H, Morishima M, Huynh T, Pramparo T . Tbx1 haploinsufficieny in the DiGeorge syndrome region causes aortic arch defects in mice. Nature. 2001; 410(6824):97-101. DOI: 10.1038/35065105. View

10.

Ingram W, McCue K, Tran T, Hallahan A, Wainwright B . Sonic Hedgehog regulates Hes1 through a novel mechanism that is independent of canonical Notch pathway signalling. Oncogene. 2007; 27(10):1489-500. DOI: 10.1038/sj.onc.1210767. View

11.

Ohtsuka T, Sakamoto M, Guillemot F, Kageyama R . Roles of the basic helix-loop-helix genes Hes1 and Hes5 in expansion of neural stem cells of the developing brain. J Biol Chem. 2001; 276(32):30467-74. DOI: 10.1074/jbc.M102420200. View

12.

Piotrowski T, Ahn D, Schilling T, Nair S, Ruvinsky I, Geisler R . The zebrafish van gogh mutation disrupts tbx1, which is involved in the DiGeorge deletion syndrome in humans. Development. 2003; 130(20):5043-52. DOI: 10.1242/dev.00704. View

13.

Li L, Krantz I, Deng Y, Genin A, Banta A, Collins C . Alagille syndrome is caused by mutations in human Jagged1, which encodes a ligand for Notch1. Nat Genet. 1997; 16(3):243-51. DOI: 10.1038/ng0797-243. View

14.

Gessler M, Knobeloch K, Helisch A, Amann K, Schumacher N, Rohde E . Mouse gridlock: no aortic coarctation or deficiency, but fatal cardiac defects in Hey2 -/- mice. Curr Biol. 2002; 12(18):1601-4. DOI: 10.1016/s0960-9822(02)01150-8. View

15.

Lindsay E, Baldini A . Recovery from arterial growth delay reduces penetrance of cardiovascular defects in mice deleted for the DiGeorge syndrome region. Hum Mol Genet. 2001; 10(9):997-1002. DOI: 10.1093/hmg/10.9.997. View

16.

Prescott K, Ivins S, Hubank M, Lindsay E, Baldini A, Scambler P . Microarray analysis of the Df1 mouse model of the 22q11 deletion syndrome. Hum Genet. 2005; 116(6):486-96. DOI: 10.1007/s00439-005-1274-3. View

17.

de la Pompa J, Wakeham A, Correia K, Samper E, Brown S, Aguilera R . Conservation of the Notch signalling pathway in mammalian neurogenesis. Development. 1997; 124(6):1139-48. DOI: 10.1242/dev.124.6.1139. View

18.

Rochais F, Dandonneau M, Mesbah K, Jarry T, Mattei M, Kelly R . Hes1 is expressed in the second heart field and is required for outflow tract development. PLoS One. 2009; 4(7):e6267. PMC: 2707624. DOI: 10.1371/journal.pone.0006267. View

19.

Randall V, McCue K, Roberts C, Kyriakopoulou V, Beddow S, Barrett A . Great vessel development requires biallelic expression of Chd7 and Tbx1 in pharyngeal ectoderm in mice. J Clin Invest. 2009; 119(11):3301-10. PMC: 2769172. DOI: 10.1172/JCI37561. View

20.

Xu H, Cerrato F, Baldini A . Timed mutation and cell-fate mapping reveal reiterated roles of Tbx1 during embryogenesis, and a crucial function during segmentation of the pharyngeal system via regulation of endoderm expansion. Development. 2005; 132(19):4387-95. DOI: 10.1242/dev.02018. View