Retinoic acid down‐regulates <i>Tbx1</i> expression in vivo and in vitro

Roberts, Catherine; Ivins, Sarah; James, Chela; Scambler, Peter J.

doi:10.1002/dvdy.20268

Cited by 103 publications

(97 citation statements)

References 67 publications

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“…7 E and F). In contrast, RA-induced down-regulation of mesodermal Tbx1 in these same embryos, which has been shown to require protein synthesis (21), was blocked ( Fig. 6 C and F, bracket), verifying that protein synthesis was inhibited in our experimental system.…”

Section: Ra Induction Of Otic Tbx1 Transcription Occurs Rapidly Andsupporting

confidence: 68%

Transient retinoic acid signaling confers anterior-posterior polarity to the inner ear

Bok

Raft

Kong

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

102

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Vertebrate hearing and balance are based in complex asymmetries of inner ear structure. Here, we identify retinoic acid (RA) as an extrinsic signal that acts directly on the ear rudiment to affect its compartmentalization along the anterior-posterior axis. A rostrocaudal wave of RA activity, generated by tissues surrounding the nascent ear, induces distinct responses from anterior and posterior halves of the inner ear rudiment. Prolonged response to RA by posterior otic tissue correlates with Tbx1 transcription and formation of mostly nonsensory inner ear structures. By contrast, anterior otic tissue displays only a brief response to RA and forms neuronal elements and most sensory structures of the inner ear.axial specification | developmental compartments | morphogen N ormal hearing and balance require that discrete patches of mechanosensory hair cells, each with a distinct function, be precisely positioned within the asymmetric membranous labyrinth of the inner ear (Fig. 1A). Five vestibular sensory patches are present in all vertebrate inner ears: the three cristae (anterior, lateral, and posterior) that detect angular head movements and two maculae (utricle and saccule) that detect linear acceleration. The specialized organ for detecting sound in chickens and mammals is the basilar papilla and organ of Corti, respectively.The entire membranous labyrinth and its innervating neurons are derived from an ectodermal thickening adjacent to the hindbrain known as the otic placode. As the placode deepens to form a cup and then pinches off to form the otocyst, some cells of the otic epithelium delaminate to form neuroblasts of the cochleovestibular ganglion (CVG). Inner ear sensory organs, and the neurons that innervate them, are thought to arise from a neural-sensory competent domain (NSD), most of which is located in the anterior region of the otic cup (1). By contrast, posterior otic epithelium forms nonsensory tissues and only one sensory organ, the posterior crista. This basic organization of functional elements in the ear is thought to be governed by signals emanating from adjacent tissues (2, 3); however, molecular mechanisms that establish the initial anterior-posterior (A-P) asymmetry of the ear primordium are poorly defined. Here, we show that a rostrocaudal wave of retinoic acid activity provides signals to the ear rudiment and establishes structural asymmetries required for normal hearing and balance. ResultsEctoderm Adjacent to the Otic Cup Confers A-P Polarity to the Otocyst. A clear manifestation of A-P asymmetry in developing amniote ears is the anterior expression of transcripts associated with cochleovestibular ganglion neurogenesis. We performed tissue transplantations in ovo to identify source(s) of signals that specify the otic A-P axis in the chicken. Transplantations were carried out at the otic cup stage (11-15 somite stages), before the otic A-P axis is specified (4). As expected, reversing the A-P orientation of the otic cup alone resulted in a high occurrence of otocysts with the axial plan...

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Section: Ra Induction Of Otic Tbx1 Transcription Occurs Rapidly Andsupporting

confidence: 68%

Transient retinoic acid signaling confers anterior-posterior polarity to the inner ear

Bok

Raft

Kong

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

102

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“…Moreover, environmental factors may also be important modifiers of the expressivity of TBX1 mutations. For example, TBX1 is inhibited by retinoic acid 30,31 and thus low levels of retinoic acid during development could exacerbate the effects of TBX1 mutations that increase protein levels. Therefore, any environmental factor that interferes with vitamin A metabolism (e.g., alcohol intake) could also potentially affect TBX1 expression during development.…”

Section: Discussionmentioning

confidence: 99%

Mutations in TBX1 genocopy the 22q11.2 deletion and duplication syndromes: a new susceptibility factor for mental retardation

et al. 2007

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A screen for TBX1 gene mutations identified two mutations in patients with some features compatible with the 22q11.2-deletion syndrome but with no deletions. One is a de novo missense mutation and the other is a 5 0 untranslated region (5 0 UTR) C4T change that affects a nucleotide with a remarkable trans-species conservation. Computer modelling shows that the 5 0 UTR change is likely to affect the mRNA structure and in vitro translation experiments demonstrate that it produces a twofold increase in translation efficiency. Recently, duplications in the 22q11.2 region were reported in patients referred for fragile-X determination because of cognitive and behavioural problems. Because the 5 0 UTR nucleotide change may be a functional equivalent of a duplication of the TBX1 gene, we decided to screen 200 patients who had been referred for fragile-X determination and 400 healthy control individuals. As a result, we found the 5 0 UTR mutation to be present in three patients with mental retardation or behavioural problems and absent in control individuals of the same ethnic background. This observation suggests that it may be reasonable to screen for such mutation among patients with unspecific cognitive deficits and we provide an easy and quick way to do it with an amplification refractory mutation system (ARMS) approach. To our knowledge, this is the first human mutation showing that TBX1 is a candidate causing mental retardation associated with the 22q11.2 duplication syndrome.

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“…Mesodermal tbx1 expression is modulated bimodally by levels of retinoic acid and by Shh signaling via Fox transcription factors. Tbx1 in turn regulates expression of fgf10 and, additionally, in the secondary heart field, fgf8 (Garg et al, 2001;Yamagishi et al, 2003;Roberts et al, 2005). Functional T-box binding sites have been identified in the Xenopus myf5 promoter, suggesting a cellautonomous role (Lin et al, 2003).…”

Section: Molecular Biographies Of Developing Head Musclesmentioning

confidence: 99%

The differentiation and morphogenesis of craniofacial muscles

Noden

Francis‐West

2006

Developmental Dynamics

349

357

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Unraveling the complex tissue interactions necessary to generate the structural and functional diversity present among craniofacial muscles is challenging. These muscles initiate their development within a mesenchymal population bounded by the brain, pharyngeal endoderm, surface ectoderm, and neural crest cells. This set of spatial relations, and in particular the segmental properties of these adjacent tissues, are unique to the head. Additionally, the lack of early epithelialization in head mesoderm necessitates strategies for generating discrete myogenic foci that may differ from those operating in the trunk. Molecular data indeed indicate dissimilar methods of regulation, yet transplantation studies suggest that some head and trunk myogenic populations are interchangeable. The first goal of this review is to present key features of these diversities, identifying and comparing tissue and molecular interactions regulating myogenesis in the head and trunk. Our second focus is on the diverse morphogenetic movements exhibited by craniofacial muscles. Precursors of tongue muscles partly mimic migrations of appendicular myoblasts, whereas myoblasts destined to form extraocular muscles condense within paraxial mesoderm, then as large cohorts they cross the mesoderm:neural crest interface en route to periocular regions. Branchial muscle precursors exhibit yet another strategy, establishing contacts with neural crest populations before branchial arch formation and maintaining these relations through subsequent stages of morphogenesis. With many of the prerequisite stepping-stones in our knowledge of craniofacial myogenesis now in place, discovering the cellular and molecular interactions necessary to initiate and sustain the differentiation and morphogenesis of these neglected craniofacial muscles is now an attainable goal.

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Retinoic acid down‐regulates Tbx1 expression in vivo and in vitro

Cited by 103 publications

References 67 publications

Transient retinoic acid signaling confers anterior-posterior polarity to the inner ear

Transient retinoic acid signaling confers anterior-posterior polarity to the inner ear

Mutations in TBX1 genocopy the 22q11.2 deletion and duplication syndromes: a new susceptibility factor for mental retardation

The differentiation and morphogenesis of craniofacial muscles

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