A role for Tbx5 in proepicardial cell migration during cardiogenesis

Hatcher, Cathy J.; Diman, Nata Y; Kim, Minsu; Pennisi, David J.; Song, Yee Jiun; Goldstein, Martin; Matsukawa, Takashi; Basson, Craig T.

doi:10.1152/physiolgenomics.00060.2004

Cited by 95 publications

(101 citation statements)

References 71 publications

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“…[37][38][39][40] Patients with whole or partial chromosome 12q duplications (including the 12q24.21 region and TBX5 gene) have been described to have some of the cardiac features of HOS (mainly septal defects), other congenital anomalies and dysmorphism, but hardly any of the skeletal features. [41][42][43][44][45][46][47][48][49] This partially conforms to the prominent cardiac defects and milder limb defects seen in this family with the TBX5 duplication, therefore it seems expression of TBX5 must be finely regulated for normal cardiac and limb development.…”

Section: Discussionmentioning

confidence: 99%

TBX5 intragenic duplication: a family with an atypical Holt–Oram syndrome phenotype

Patel

Silcock²,

McMullan³

et al. 2012

Eur J Hum Genet

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Holt-Oram syndrome (HOS) is a rare autosomal dominant heart-hand syndrome due to mutations in the TBX5 transcription factor. Affected individuals can have structural cardiac defects and/or conduction abnormalities, and exclusively upper limb defects (typically bilateral, asymmetrical radial ray defects). TBX5 mutations reported include nonsense, missense, splicing mutations and exon deletions. Most result in a null allele and haploinsufficiency, but some impair nuclear localisation of TBX5 protein or disrupt its interaction with co-factors and downstream targets. We present a five generation family of nine affected individuals with an atypical HOS phenotype, consisting of ulnar ray defects (ulnar hypoplasia, short fifth fingers with clinodactyly) and very mild radial ray defects (short thumbs, bowing of the radius and dislocation of the radial head). The cardiac defects seen are those more rarely reported in HOS (atrioventricular septal defect, hypoplastic left heart syndrome, mitral valve disease and pulmonary stenosis). Conduction abnormalities include atrial fibrillation, atrial flutter and sick sinus syndrome. TBX5 mutation screening (exons 3-10) identified no mutations. Array comparative genomic hybridisation (CGH) revealed a 48 kb duplication at 12q24.21, encompassing exons 2-9 of the TBX5 gene, with breakpoints within introns 1-2 and 9-10. The duplication segregates with the phenotype in the family, and is likely to be pathogenic. This is the first known report of an intragenic duplication of TBX5 and its clinical effects; an atypical HOS phenotype. Further functional studies are needed to establish the effects of the duplication and pathogenic mechanism. All typical/atypical HOS cases should be screened for TBX5 exon duplications.

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Section: Discussionmentioning

confidence: 99%

TBX5 intragenic duplication: a family with an atypical Holt–Oram syndrome phenotype

Patel

Silcock²,

McMullan³

et al. 2012

Eur J Hum Genet

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“…CKB is one of the genes most affected by Tbx5 in the microarray analysis of 1H cells and is dramatically induced in primary E14.5 cardiomyocytes, consistent with Tbx5 regulation of CKB during myogenesis. Tbx5 is also implicated in the inhibition of cardiomyocyte proliferation and proepicardial migration and induces the expression of the cell-cycle arrest gene p57 kip2 and the epicardial marker WT1 (Kochilas et al, 1999;Moore et al, 1999;Hatcher et al, 2001Hatcher et al, , 2004. Tbx5 induction of these genes may contribute to reported functions of Tbx5 in differentiation, proliferation, and epicardial development.…”

Section: Discussionmentioning

confidence: 99%

Microarray analysis of Tbx5‐induced genes expressed in the developing heart

Plageman

Yutzey

2006

Developmental Dynamics

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Tbx5 is a member of the T-box family of transcription factors and is associated with Holt-Oram syndrome (HOS), a congenital disorder characterized by heart and limb defects. Although implicated in several processes during development, only a few genes regulated by Tbx5 have been reported. To identify candidate genes regulated by Tbx5 during heart development, a microarray approach was used. A cardiacderived mouse cell line (1H) was infected with adenoviruses expressing Tbx5 or ␤-galactosidase and RNA was isolated for analysis using an Affymetrix gene chip representing over 39,000 transcripts. Real-time reverse transcriptase-polymerase chain reaction confirmed Tbx5 induction of a subset of the genes, including nppa, photoreceptor cadherin, brain creatine kinase, hairy/enhancer-of-split related 2, and gelsolin. In situ hybridization analysis indicated overlapping expression of these genes with tbx5 in the embryonic mouse heart. In addition, the effect of HOS-associated mutations on the ability of Tbx5 to induce target gene expression was evaluated. Together, these data identify several genes induced by Tbx5 that are potentially important during cardiac development. These genes represent new candidate gene targets of Tbx5 that may be related to congenital heart malformations associated with HOS. Developmental Dynamics 235:2868 -2880, 2006.

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“…Since these T-box genes are expressed in the epicardial cell layer of the heart and its progenitors (Plageman et al 2005;Kraus et al 2001;Hatcher et al 2004;Tanaka et al 2004), PACPs may belong to an epicardial progenitor population ( Figure 28, Table 7). …”

Section: Discussionmentioning

confidence: 99%

“…Together, these T-box genes likely contribute to cardiac lineage determination, chamber specification, valve formation, epicardial development and specialization of the conduction system (Plageman et al 2005). T-box genes, including Tbx18 and Tbx5 are also expressed in the epicardial cell layer of the heart and its progenitors (Kraus et al 2001;Hatcher et al 2004;Tanaka and Tickle 2004 Figure 4. Illustration of stem cell control by the niche (Secker et al 2009).…”

Section: Figure 2 Cardiogenic Pathwaysmentioning

confidence: 99%