The cleft lip and palate defects in<i>Dancer</i>mutant mice result from gain of function of the<i>Tbx10</i>gene

Bush, Jeffrey O.; Lan, Yu; Jiang, Rulang

doi:10.1073/pnas.0401025101

Cited by 46 publications

(35 citation statements)

References 46 publications

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“…In addition to the A strains of mice described above, mice homozygous for either of two spontaneous mutations, Dancer and Twirler, exhibit high penetrance of CLP (Lyon, 1958;Deol andLane, 1966, Gong et al, 2000). Whereas the Twirler gene remains to be identified, Bush et al (2004) recently positionally cloned the Dancer mutation and showed that the CLP phenotype in the Dancer homozygous mutants results from widespread misexpression of the Tbx10 gene due to insertion of a heterologous promoter. How Tbx10 misexpression disrupts the normal molecular and cellular programs of facial morphogenesis remains to be determined.…”

Section: Other Genes and Pathwaysmentioning

confidence: 99%

Development of the upper lip: Morphogenetic and molecular mechanisms

Jiang

Bush

Lidral

2005

Developmental Dynamics

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285

304

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The vertebrate upper lip forms from initially freely projecting maxillary, medial nasal, and lateral nasal prominences at the rostral and lateral boundaries of the primitive oral cavity. These facial prominences arise during early embryogenesis from ventrally migrating neural crest cells in combination with the head ectoderm and mesoderm and undergo directed growth and expansion around the nasal pits to actively fuse with each other. Initial fusion is between lateral and medial nasal processes and is followed by fusion between maxillary and medial nasal processes. Fusion between these prominences involves active epithelial filopodial and adhering interactions as well as programmed cell death. Slight defects in growth and patterning of the facial mesenchyme or epithelial fusion result in cleft lip with or without cleft palate, the most common and disfiguring craniofacial birth defect. Recent studies of craniofacial development in animal models have identified components of several major signaling pathways, including Bmp, Fgf, Shh, and Wnt signaling, that are critical for proper midfacial morphogenesis and/or lip fusion. There is also accumulating evidence that these signaling pathways cross-regulate genetically as well as crosstalk intracellularly to control cell proliferation and tissue patterning. This review will summarize the current understanding of the basic morphogenetic processes and molecular mechanisms underlying upper lip development and discuss the complex interactions of the various signaling pathways and challenges for understanding cleft lip pathogenesis.

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Section: Other Genes and Pathwaysmentioning

confidence: 99%

Development of the upper lip: Morphogenetic and molecular mechanisms

Jiang

Bush

Lidral

2005

Developmental Dynamics

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285

304

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“…Notably, mice lacking TBX2 in the developing palate develop a cleft palate and show increased cell proliferation in the palatal shelves (Zirzow et al, 2009). Moreover, mice homozygous for the spontaneous Dancer (Dc) mutation, in which a p23-Tbx10 chimeric transcript is ectopically expressed, or transgenic mice with a ubiquitous CMVb-driven expression of Tbx10 exhibited cleft lip and cleft palate (Bush et al, 2004). This clearly illustrates that gain of expression of a T-box transcription factor gene other than TBX22 can cause facial clefts.…”

Section: Functions Of Tbx22 Downstream Of Fgf and Bmp Signaling In Dementioning

confidence: 99%

Regulation of Tbx22 during facial and palatal development

Fuchs

Inthal

Herrmann

et al. 2010

Developmental Dynamics

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Mutations in the gene encoding the T-box transcription factor TBX22 cause X-linked cleft palate and ankyloglossia in humans. Here we show that Tbx22 expression during facial and palatal development is regulated by FGF and BMP signaling. Our results demonstrate that FGF8 induces Tbx22 in the early face while BMP4 represses and thus restricts its expression. This regulation is conserved between chicken and mouse, although the Tbx22-expression patterns differ considerably between these two species. We suggest that these species-specific differences may result at least in part from differences in the spatiotemporal patterns of BMP activity, but we exclude a direct repression of Tbx22 by the BMP-inducible transcriptional repressor MSX1. Together these findings help to integrate Tbx22 into the molecular network of factors regulating facial development. Developmental Dynamics 239:2860-2874,

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“…Expression analyses in the mouse secondary palate reveal that the strongest expression of Satb2 occurs before palatal shelf fusion (E13.5), with a dramatic down-regulation after the shelves have fused (E14.5) (Figure 2). Additional examples of clefts arising from displaced genomic material are the Dancer mutation [35] and clefts in the 22q and 1p36 deletion syndromes [36,37].…”

Section: Clues From Genomic Rearrangementsmentioning

confidence: 99%

“…Both the Dancer and Twirler mutations are almost fully penetrant for CL/P in homozygotes. Furthermore, Dancer was shown to arise from a translocation of the p23 gene sequence into the Tbx10 locus, resulting in ectopic expression of Tbx10 under the influence of the p23 promoter [35].…”

Section: Animal Models and Expression Datamentioning

confidence: 99%

Orofacial clefting: recent insights into a complex trait

Jugessur

Murray

2005

Current Opinion in Genetics & Development

192

168

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Orofacial clefts are common birth defects of multifactorial etiology. Several novel approaches have recently been applied to investigate the causes of clefts. These include examining Mendelian forms of clefting to identify genes that might also be implicated in isolated clefting, analyzing chromosomal rearrangements in which clefting is part of the resultant phenotype, studying animal models in which clefts arise either spontaneously or as a result of mutagenesis experiments, exploring how expression patterns correlate with gene function and examining the effects of gene-environment interactions. Together, these complementary strategies are providing researchers with new clues as to what mechanisms underlie orofacial clefting.

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The cleft lip and palate defects inDancermutant mice result from gain of function of theTbx10gene

Cited by 46 publications

References 46 publications

Development of the upper lip: Morphogenetic and molecular mechanisms

Development of the upper lip: Morphogenetic and molecular mechanisms

Regulation of Tbx22 during facial and palatal development

Orofacial clefting: recent insights into a complex trait

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