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 language | English |
|---|---|
| Pages (from-to) | 554-569 |
| Number of pages | 16 |
| Journal | Developmental Biology |
| Volume | 285 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - Sep 15 2005 |
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Keywords
- 22q11 deletion
- DiGeorge syndrome
- Expression microarray
- Pharyngeal development Tbx1
ASJC Scopus subject areas
- Developmental Biology
Cite this
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 journal › Article
}
TY - JOUR
T1 - Microarray analysis detects differentially expressed genes in the pharyngeal region of mice lacking Tbx1
AU - Ivins, Sarah
AU - Van Beuren, Kelly Lammerts
AU - Roberts, Catherine
AU - James, Chela
AU - Lindsay, Elizabeth
AU - Baldini, Antonio
AU - Ataliotis, Paris
AU - Scambler, Peter J.
PY - 2005/9/15
Y1 - 2005/9/15
N2 - 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.
AB - 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.
KW - 22q11 deletion
KW - DiGeorge syndrome
KW - Expression microarray
KW - Pharyngeal development Tbx1
UR - http://www.scopus.com/inward/record.url?scp=25844503071&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=25844503071&partnerID=8YFLogxK
U2 - 10.1016/j.ydbio.2005.06.026
DO - 10.1016/j.ydbio.2005.06.026
M3 - Article
C2 - 16109395
AN - SCOPUS:25844503071
VL - 285
SP - 554
EP - 569
JO - Developmental Biology
JF - Developmental Biology
SN - 0012-1606
IS - 2
ER -