Wnt signaling mediates regional specification in the vertebrate face

Brugmann, Samantha A.; Goodnough, L. Henry; Gregorieff, Alex; Leucht, Philipp; Berge, Derk ten; Fuerer, Christophe; Clevers, Hans; Nusse, Roel; Helms, Jill A.

doi:10.1242/dev.005132

Cited by 201 publications

(219 citation statements)

References 67 publications

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“…In amniotes, snout length is associated with the relative contributions of the frontonasal prominence, derived from rostrally migrating cells, and the maxillary prominence, derived from caudally migrating cells, to the facial skeleton 33,34 . Therefore, the evolution of skull morphology could utilize miRNAs, in particular Mirn140, to tweak the number of crest cells arriving at an individual prominence within the first pharyngeal arch.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA Mirn140 modulates Pdgf signaling during palatogenesis

et al. 2008

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Disruption of signaling pathways such as those mediated by Shh or Pdgf causes craniofacial disease, including cleft palate. The role that microRNAs play in modulating palatogenesis, however, is completely unknown. We show, in zebrafish, that the microRNA Mirn140 negatively regulates Pdgf signaling during palatal development and we provide a mechanism for how disruption of Pdgf signaling causes palatal clefting. The pdgf-receptor alpha (pdgfra) 3' UTR contains a Mirn140 binding site functioning in the negative regulation of Pdgfra protein levels in vivo. Both pdgfra mutants and Mirn140-injected embryos share panoply of facial defects including clefting of the crestderived cartilages that develop in the roof of the larval mouth. Concomitantly, the oral ectoderm beneath where these cartilages develop loses pitx2 and shha expression. Mirn140 modulates Pdgfmediated attraction of cranial neural crest cells to the oral ectoderm, where crest-derived signals are necessary for oral ectodermal gene expression. Both Mirn140 loss-of-function and pdgfra overexpression alters palatal shape and causes neural crest cells to accumulate around the optic stalk, a source of the ligand Pdgfaa. Conserved molecular genetics and expression patterns of mirn140 and pdgfra suggest that their regulatory interactions are ancient methods of palatogenesis that provide a candidate mechanism for cleft palate.Cleft palate and other craniofacial diseases are common in humans and have complex cellular and genetic etiologies. In amniotes, the palate serves to separate the nasal and oral cavities and is generated through an intricate series of morphogenic events that include early neural crest cell migration and cell-cell signaling during the formation of facial prominences, as well as later generation and fusion of palatal shelves. While later events involving palatal shelves have not been described in zebrafish, palatal precursors migrate both rostral and caudal to the eye to condense upon the oral ectoderm in amniotes 1 as well as zebrafish 2,3 and evidence continues to accumulate that the early signaling environment governing palatogenesis is also largely equivalent [3][4][5][6] . For instance, Hh signaling is crucial for palatogenesis in humans and zebrafish 3,4,7 . Zebrafish and amniotes also share expression patterns of palatogenic genes such as Shh 4,8 , Fgf8 4,9,10 and Pdgf receptor alpha (Pdgfra) [11][12][13] .In mouse, the Pdgf family consists of four soluble ligands, Pdgfa, Pdgfb, Pdgfc, and Pdgfd as well as two receptor tyrosine kinases, Pdgfra and Pdgfrb 14 . Pdgf signaling regulates a myriad of biological processes as demonstrated by analyses of mouse Pdgf ligand and receptor mutants 14 . Mice null for Pdgfra have a facial clefting phenotype that includes cleft palate 12,13 . This facial phenotype is fully recapitulated in mice doubly mutant for Pdgfa and Pdgfc 15. Most Pdgfc mutants have cleft palate 15 MicroRNAs (miRNAs) provide a unique mechanism for modulating signaling pathways [17][18][19][20] . Skeletogenic, including...

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Section: Discussionmentioning

confidence: 99%

MicroRNA Mirn140 modulates Pdgf signaling during palatogenesis

et al. 2008

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“…Enters cells very efficiently including in post-mitotic cells (Brugmann et al, 2007;Howarth et al, 2010). All cationic lipds are similar, they contain a positive headgroup and a hydrophobic tail .…”

Section: Adenovirusmentioning

confidence: 99%

Development of high-concentration lipoplexes for in vivo gene function studies in vertebrate embryos

et al. 2011

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Here we report that highly concentrated cationic lipid/helper lipid‐nucleic acid complexes (lipoplexes) can facilitate reproducible delivery of a variety of oligonucleotides and plasmids to chicken embryos or to mouse embryonic mesenchyme. Specifically, liposomes composed of N,N‐dioleyl‐N,N‐dimethylammonium chloride (DODAC)/1,2 dioleoyl glycero‐3‐phosphorylethanolamine (DOPE) prepared at 18‐mM concentrations produced high levels of transfection of exogenous genes in vivo and in vitro. Furthermore, we report sufficient uptake of plasmids expressing interference RNA to decrease expression of both exogenous and endogenous genes. The simplicity of preparation, implementation, and relatively low toxicity of this transfection reagent make it an attractive alternative for developmental studies in post‐gastrulation vertebrate embryos. Developmental Dynamics 240:2108–2119, 2011. © 2011 Wiley‐Liss, Inc.

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“…One pathway, for which different activation patterns have recently been described during chick and mouse facial development, and that is active in similar regions as Msx1, is the WNT signaling pathway (Brugmann et al, 2007). Whether WNT signaling has any influence on Tbx22 expression, however, is currently unknown.…”

Section: Fgf and Bmp Signaling Pathways Converge On The Regulation Ofmentioning

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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Wnt signaling mediates regional specification in the vertebrate face

Cited by 201 publications

References 67 publications

MicroRNA Mirn140 modulates Pdgf signaling during palatogenesis

MicroRNA Mirn140 modulates Pdgf signaling during palatogenesis

Development of high-concentration lipoplexes for in vivo gene function studies in vertebrate embryos

Regulation of Tbx22 during facial and palatal development

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