Tbx5 is required for forelimb bud formation and continued outgrowth

Rallis, Charalampos; Bruneau, Benoit G.; Buono, Jo Del; Seidman, Christine E.; Seidman, Jonathan G.; Nissim, Sahar; Tabin, Clifford J.; Logan, Malcolm

doi:10.1242/dev.00473

Cited by 212 publications

(254 citation statements)

References 57 publications

(71 reference statements)

Supporting

Mentioning

245

Contrasting

Unclassified

Order By: Relevance

“…Among the genes listed in Table 1, are those implicated in many aspects of heart development that have also been associated with Tbx5 and are involved in cardiac septation (hey2, odd-skipped related 1), proliferation inhibition (p57 kip2 ), myogenic differentiation (skeletal alpha-actin, titin, cardiac troponin T2), and epicardial development (WT1). Several of the genes also have reported function or expression in regions outside of the heart where Tbx5 is expressed, such as the forelimb and retina (Table 1; Koshiba-Takeuchi et al, 2000;Agarwal et al, 2003;Rallis et al, 2003). In this report, the genes nppa, phospholipase A2 group IIE (pla2g2e), photoreceptor cadherin (prCAD), brain creatine kinase (CKB), hairy/enhancerof-split related 2 (hey2), and gelsolin were chosen for further study based on previously reported cardiac function or expression and relatively large statistically significant fold changes detected in the microarray.…”

Section: Identification Of Tbx5-induced Genes By Microarray Analysismentioning

confidence: 99%

“…Mice heterozygous null for tbx5 display atrioventricular block, a disruption in conduction system function that resembles what is observed in HOS (Bruneau et al, 2001;Moskowitz et al, 2004). In addition to processes related to cardiogenesis, embryonic limb development and retinal patterning are affected in loss or gain of function studies of Tbx5 (Koshiba-Takeuchi et al, 2000;Agarwal et al, 2003;Rallis et al, 2003). Taken together, it is clear that Tbx5 is an important regulator of many processes during embryonic development; however, the full complement of genes regulated by Tbx5 are only beginning to emerge.…”

Section: Introductionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

“…Tbx5 directly activates the promoters of connexin 40 (Cx40), natriuretic peptide precursor A (nppa), and fibroblast growth factor 10 (fgf10), and expression of these genes is significantly reduced in mice that lack tbx5 (Bruneau et al, 2001;Rallis et al, 2003). fgf10 is required for limb bud outgrowth, and reduced fgf10 expression in the absence of Tbx5 is associated with the abnormal development of the forelimbs in Tbx5 mutant mice (Rallis et al, 2003). Proper electrophysiological function of the heart is dependent on the gap junction protein Cx40 (Kirchhoff et al, 1998;Simon et al, 1998), and reduction in its expression is hypothesized to affect the conduction system in HOS (Bruneau et al, 2001;Moskowitz et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

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

Plageman

Yutzey

2006

Developmental Dynamics

View full text Add to dashboard Cite

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.

show abstract

Section: Identification Of Tbx5-induced Genes By Microarray Analysismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

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

Plageman

Yutzey

2006

Developmental Dynamics

View full text Add to dashboard Cite

show abstract

“…An asterisk indicates the ablated side. for forelimb bud initiation (Ng et al, 2002;Takeuchi et al, 2003;Rallis et al, 2003;Hasson et al, 2007). Tbx5 is not expressed in the LPM before stage 13 in the chick embryo (Saito et al, 2002), and the LPM fate for forelimb-flank-hindlimb regionalization can be altered up to stage 13 (Saito et al, 2002(Saito et al, , 2006.…”

Section: Developmental Dynamicsmentioning

confidence: 99%

Role of paraxial mesoderm in limb/flank regionalization of the trunk lateral plate

Noro

Yuguchi

Sato

et al. 2011

Developmental Dynamics

View full text Add to dashboard Cite

To understand the developmental mechanism that determines limb size and the consequent limb-to-trunk proportions in the tetrapod body, we investigated the role of the paraxial mesoderm in the specification of the limb and flank fields in the chick embryo. We found that the paraxial mesoderm subjacent to the limb field can affect the size of the limb bud along the anterior-posterior and proximal-distal axes. We also found that the paraxial mesoderm subjacent to the flank plays roles in suppressing the emergence and growth of the limb bud and in promoting flank-specific apoptosis in the lateral plate mesoderm. Our results suggest that signals from the paraxial mesoderm specify the limb and flank fields in the competent lateral plate mesoderm.

show abstract

Vertebrate Embryo: Limb Development

Tickle

2016

Encyclopedia of Life Sciences

View full text Add to dashboard Cite

Vertebrate limbs develop from small buds of mesenchyme cells encased in ectoderm. Limb development is an excellent model system for studying embryonic growth and pattern formation. Both processes are governed by cell–cell interactions involving signalling centres that operate along each of the three limb axes, but are functionally interconnected. The main proliferative and positional signals are WNTs, FGFs, SHH and BMPs. Considerable progress has been made in identifying molecules that initiate bud formation including the TBX4/5 transcription factors and unravelling the regulatory pathways that establish the signalling centres. Hox genes are involved in multiple steps in establishing the anteroposterior signalling centre in the forelimb. They are also expressed in response to positional signals in the limb buds with a late‐phase controlling digit development. The transcription factor, LMX1B, specifies dorsal development. The transcription factor PITX1 is a major hindlimb determinant but how positional information is interpreted is largely unknown. Key Concepts The limb develops from a bud of mesoderm cells encased in ectoderm which grows out from the body wall. The limb bud mesoderm is made up of cells with two different origins; cells of the lateral plate mesoderm which give rise to the connective tissues and cells that have migrated from the somites which give rise to the myogenic cells of the limb muscles. Three sets of cell–cell interactions specify positional information; one set of interactions operating along each of the three axes of the limb. The apical ectodermal ridge at the tip of the limb bud produces FGFs which are required for bud outgrowth and laying down the proximodistal limb pattern. The dorsal and ventral ectoderm of the limb bud produce WNT7a and BMPs, respectively, which are involved in specifying dorsoventral positional information. The polarising region, a mesodermal signalling region at the posterior margin of the limb bud, produces Sonic Hedgehog (SHH) which specifies anteroposterior positional information and controls growth across this axis. Hox5 and Hox9 paralogous genes of the Hox clusters are involved in establishing the initial anteroposterior polarity of the buds that will develop into forelimbs. Interactions between the signalling regions ensure that pattern formation is integrated along all three axes of the developing limb. 5′ genes in the HoxA and HoxD clusters are expressed in early and late limb buds under the control of long‐range enhancers located, respectively, 3′ and 5′ of the cluster, with the early phase of activity being involved in establishing Shh expression in the polarising region and the later phase development of the digits. The differences between forelimbs and hindlimbs depend on the interpretation of positional information, with the transcription factor PITX1 being a major hindlimb determinant.

show abstract

Tbx5 is required for forelimb bud formation and continued outgrowth

Cited by 212 publications

References 57 publications

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

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

Role of paraxial mesoderm in limb/flank regionalization of the trunk lateral plate

Vertebrate Embryo: Limb Development

Contact Info

Product

Resources

About