Microarray analysis detects differentially expressed genes in the pharyngeal region of mice lacking Tbx1

Sarah Ivins, Kelly Lammerts Van Beuren, Catherine Roberts, Chela James, Elizabeth Lindsay, Antonio Baldini, Paris Ataliotis, Peter J. Scambler

Research output: Contribution to journalArticle

68 Citations (Scopus)

Abstract

22q11-deletion (DiGeorge/velocardiofacial) syndrome (22q11DS) is modeled by mutation of murine transcription factor Tbx1. As part of efforts to identify transcriptional targets of Tbx1, we analyzed the transcriptome of the pharyngeal region of Df1/+;Tbx1+/- embryos at 9.5 days of embryonic development using two independent microarray platforms. In this model, embryos are null for Tbx1, with hemizygosity of genes in cis with Tbx1 on one chromosome providing a positive control for array sensitivity. Reduced mRNA levels of genes deleted from Df1 were detected on both platforms. Expression level filtering and statistical analysis identified several genes that were consistently differentially expressed between mutant and wild type embryos. Real-time quantitative PCR and in situ hybridization validated diminished expression of Pax9 and Gcm2, genes known to be required for normal thymus and parathyroid gland morphogenesis, whereas Pax1, Hoxa3, Eya1, and Foxn1, which are similarly required, were not down-regulated. Gbx2, a gene required for normal arch artery development, was down-regulated specifically in the pharyngeal endoderm and the posterior part of pharyngeal arch 1, and is a potential point of cross talk between the Tbx1 and Fgf8 controlled pathways. These experiments highlight which genes and pathways potentially affected by lack of Tbx1, and whose role may be explored further by testing for epistasis using mouse mutants.

Original languageEnglish
Pages (from-to)554-569
Number of pages16
JournalDevelopmental Biology
Volume285
Issue number2
DOIs
Publication statusPublished - Sep 15 2005

Fingerprint

Microarray Analysis
Genes
DiGeorge Syndrome
Embryonic Structures
Branchial Region
Endoderm
Parathyroid Glands
Morphogenesis
Transcriptome
Thymus Gland
Embryonic Development
In Situ Hybridization
Real-Time Polymerase Chain Reaction
Transcription Factors
Arteries
Chromosomes
Messenger RNA
Mutation

Keywords

  • 22q11 deletion
  • DiGeorge syndrome
  • Expression microarray
  • Pharyngeal development Tbx1

ASJC Scopus subject areas

  • Developmental Biology

Cite this

Ivins, S., Van Beuren, K. L., Roberts, C., James, C., Lindsay, E., Baldini, A., ... Scambler, P. J. (2005). Microarray analysis detects differentially expressed genes in the pharyngeal region of mice lacking Tbx1. Developmental Biology, 285(2), 554-569. https://doi.org/10.1016/j.ydbio.2005.06.026

Microarray analysis detects differentially expressed genes in the pharyngeal region of mice lacking Tbx1. / Ivins, Sarah; Van Beuren, Kelly Lammerts; Roberts, Catherine; James, Chela; Lindsay, Elizabeth; Baldini, Antonio; Ataliotis, Paris; Scambler, Peter J.

In: Developmental Biology, Vol. 285, No. 2, 15.09.2005, p. 554-569.

Research output: Contribution to journalArticle

Ivins, S, Van Beuren, KL, Roberts, C, James, C, Lindsay, E, Baldini, A, Ataliotis, P & Scambler, PJ 2005, 'Microarray analysis detects differentially expressed genes in the pharyngeal region of mice lacking Tbx1', Developmental Biology, vol. 285, no. 2, pp. 554-569. https://doi.org/10.1016/j.ydbio.2005.06.026
Ivins, Sarah ; Van Beuren, Kelly Lammerts ; Roberts, Catherine ; James, Chela ; Lindsay, Elizabeth ; Baldini, Antonio ; Ataliotis, Paris ; Scambler, Peter J. / Microarray analysis detects differentially expressed genes in the pharyngeal region of mice lacking Tbx1. In: Developmental Biology. 2005 ; Vol. 285, No. 2. pp. 554-569.
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