Expression patterns of Hedgehog signalling pathway members during mouse palate development

Rice, Ritva; Connor, Elaine C.; Rice, David

doi:10.1016/j.modgep.2005.06.005

Cited by 75 publications

(91 citation statements)

References 17 publications

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“…Around this stage, Shh expression is observed in the pharyngeal epithelial lining (Fig. 4E,G) (Rice et al, 2006). In the primary gut, the earliest Shh expression is detected around E8.0 and is necessary for the formation of the lung, gut and urogenital organs (Haraguchi et al, 2007;Litingtung et al, 1998).…”

Section: Three Clustered Enhancers Direct Co-linear Shh Expression Almentioning

confidence: 96%

A cluster of three long-range enhancers directs regionalShhexpression in the epithelial linings

et al. 2009

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The sonic hedgehog (Shh) pathway plays indispensable roles in the morphogenesis of mouse epithelial linings of the oral cavity and respiratory and digestive tubes. However, no enhancers that regulate regional Shh expression within the epithelial linings have been identified so far. In this study, comparison of genomic sequences across mammalian species and teleost fishes revealed three novel conserved non-coding sequences (CNCSs) that cluster in a region 600 to 900 kb upstream of the transcriptional start site of the mouse Shh gene. These CNCSs drive regional transgenic lacZ reporter expression in the epithelial lining of the oral cavity, pharynx, lung and gut. Together, these enhancers recapitulate the endogenous Shh expression domain within the major epithelial linings. Notably, genomic arrangement of the three CNCSs shows co-linearity that mirrors the order of the epithelial expression domains along the anteroposterior body axis. The results suggest that the three CNCSs are epithelial lining-specific long-range Shh enhancers, and that their actions partition the continuous epithelial linings into three domains: ectoderm-derived oral cavity, endoderm-derived pharynx, and respiratory and digestive tubes of the mouse. Targeted deletion of the pharyngeal epithelium specific CNCS results in loss of endogenous Shh expression in the pharynx and postnatal lethality owing to hypoplasia of the soft palate, epiglottis and arytenoid. Thus, this long-range enhancer is indispensable for morphogenesis of the pharyngeal apparatus.

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Section: Three Clustered Enhancers Direct Co-linear Shh Expression Almentioning

confidence: 96%

A cluster of three long-range enhancers directs regionalShhexpression in the epithelial linings

et al. 2009

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“…Sonic hedgehog (Shh), a secreted protein expressed throughout the early oral epithelium, is a key early signal that drives palatal shelf outgrowth (Rice et al, 2006). Studies of mice with epithelium-specific inactivation of Shh or mesenchyme-specific inactivation of smoothened (Smo), which encodes a transmembrane protein required for transducing Shh signaling, have demonstrated that Shh signals from the epithelium to the underlying mesenchyme to promote palatal cell proliferation and outgrowth (Rice et al, 2004;Lan and Jiang, 2009).…”

Section: The Roles Of Epithelial-mesenchymal Interactionsmentioning

confidence: 99%

Palatogenesis: morphogenetic and molecular mechanisms of secondary palate development

2012

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Mammalian palatogenesis is a highly regulated morphogenetic process during which the embryonic primary and secondary palatal shelves develop as outgrowths from the medial nasal and maxillary prominences, respectively, remodel and fuse to form the intact roof of the oral cavity. The complexity of control of palatogenesis is reflected by the common occurrence of cleft palate in humans. Although the embryology of the palate has long been studied, the past decade has brought substantial new knowledge of the genetic control of secondary palate development. Here, we review major advances in the understanding of the morphogenetic and molecular mechanisms controlling palatal shelf growth, elevation, adhesion and fusion, and palatal bone formation.

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“…In the developing palatal shelf, the cell-surface receptors for Shh (Ptch1 and Smo), hedgehog signaling inhibitors (Hhip1 and Gas1), and Hh-signaling mediator (Gli-family zinc-finger transcription factors) are expressed in the palatal epithelium and mesenchyme (Rice et al, 2006). Conditional inactivation of Shh in the epithelium results in dramatic shortening of the palatal shelves and a wide cleft palate, whereas conditional inactivation of Smo in the epithelium does not disrupt palatogenesis 4231 RESEARCH ARTICLE Shh in palatal patterning and cleft palate rescue ( Hilliard et al, 2005), consistent with the model that the underlying palatal mesenchyme is the recipient of Shh signals.…”

Section: Oronasal Patterning Of the Palatal Shelfmentioning

confidence: 99%

Indirect modulation of Shh signaling by Dlx5 affects the oral-nasal patterning of palate and rescues cleft palate in Msx1-null mice

et al. 2009

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Cleft palate represents one of the most common congenital birth defects in human. During embryonic development, palatal shelves display oronasal (O-N) and anteroposterior polarity before the onset of fusion, but how the O-N pattern is established and how it relates to the expansion and fusion of the palatal shelves are unknown. Here we address these questions and show that O-N patterning is associated with the expansion and fusion of the palatal shelves and that Dlx5 is required for the O-N patterning of palatal mesenchyme. Loss of Dlx5 results in downregulation of Fgf7 and expanded Shh expression from the oral to the nasal side of the palatal shelf. This expanded Shh signaling is sufficient to restore palatal expansion and fusion in mice with compromised palatal mesenchymal cell proliferation, such as Msx1-null mutants. Exogenous Fgf7 inhibits Shh signaling and reverses the cranial neural crest (CNC) cell proliferation rescue in the Msx1/Dlx5 double knockout palatal mesenchyme. Thus, Dlx5-regulated Fgf7 signaling inhibits the expression of Shh, which in turn controls the fate of CNC cells through tissue-tissue interaction and plays a crucial role during palatogenesis. Our study shows that modulation of Shh signaling may be useful as a potential therapeutic approach for rescuing cleft palate.

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Expression patterns of Hedgehog signalling pathway members during mouse palate development

Cited by 75 publications

References 17 publications

A cluster of three long-range enhancers directs regionalShhexpression in the epithelial linings

A cluster of three long-range enhancers directs regionalShhexpression in the epithelial linings

Palatogenesis: morphogenetic and molecular mechanisms of secondary palate development

Indirect modulation of Shh signaling by Dlx5 affects the oral-nasal patterning of palate and rescues cleft palate in Msx1-null mice

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