Visualizing canonical Wnt signaling during mouse craniofacial development

Mani, Preethi; Jarrell, Andrew; Myers, John; Atit, Radhika

doi:10.1002/dvdy.22072

Cited by 67 publications

(56 citation statements)

References 22 publications

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“…4A,D,G), nuclear -catenin localization (see Fig. S2-C in the supplementary material) and Wnt signaling reporter activity (Mani et al, 2009). Simultaneously, the onset of the earliest dermal progenitor marker expression, Dermo1 (Atit et al, 2006;Li et al, 1995;Ohtola et al, 2008), was also observed in the En1 lineage-marked cells and Axin2-expressing supraorbital mesenchymal cells (Fig.…”

Section: T1mentioning

confidence: 81%

Role of canonical Wnt signaling/β-catenin viaDermo1in cranial dermal cell development

et al. 2010

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SUMMARYCranial dermis develops from cephalic mesoderm and neural crest cells, but what signal(s) specifies the dermal lineage is unclear. Using genetic tools to fate map and manipulate a cranial mesenchymal progenitor population in the supraorbital region, we show that the dermal progenitor cells beneath the surface ectoderm process canonical Wnt signaling at the time of specification. We show that Wnt signaling/-catenin is absolutely required and sufficient for Dermo1 expression and dermal cell identity in the cranium. The absence of the Wnt signaling cue leads to formation of cartilage in craniofacial and ventral trunk regions at the expense of dermal and bone lineages. Dermo1 can be a direct transcription target and may mediate the functional role of Wnt signaling in dermal precursors. This study reveals a lineage-specific role of canonical Wnt signaling/-catenin in promoting dermal cell fate in distinct precursor populations.

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Section: T1mentioning

confidence: 81%

Role of canonical Wnt signaling/β-catenin viaDermo1in cranial dermal cell development

et al. 2010

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“…5 R-U). Normal development of peripheral eye structures is also regulated by Wnt signaling (10)(11)(12)31), with Wnt2b and Fzd4 acting as the primary Wnt ligand and receptor in this context. In situ hybridization analysis of the expression pattern of Wnt2b and Fzd4 at E15.5 eye showed increased and expanded expression of both these genes in the peripheral eye of TSK −/− mice compared with WT mice (Fig.…”

Section: Wnt-3amentioning

confidence: 99%

Tsukushi functions as a Wnt signaling inhibitor by competing with Wnt2b for binding to transmembrane protein Frizzled4

Ohta

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Kuriyama

et al. 2011

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

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The Wnt signaling pathway is essential for the development of diverse tissues during embryogenesis. Signal transduction is activated by the binding of Wnt proteins to the type I receptor lowdensity lipoprotein receptor-related protein 5/6 and the seven-pass transmembrane protein Frizzled (Fzd), which contains a Wntbinding site in the form of a cysteine-rich domain. Known extracellular antagonists of the Wnt signaling pathway can be subdivided into two broad classes depending on whether they bind primarily to Wnt or to low-density lipoprotein receptor-related protein 5/6. We show that the secreted protein Tsukushi (TSK) functions as a Wnt signaling inhibitor by binding directly to the cysteine-rich domain of Fzd4 with an affinity of 2.3 × 10 −10 M and competing with Wnt2b. In the developing chick eye, TSK is expressed in the ciliary/iris epithelium, whereas Wnt2b is expressed in the adjacent anterior rim of the optic vesicle, where it controls the differentiation of peripheral eye structures, such as the ciliary body and iris. TSK overexpression effectively antagonizes Wnt2b signaling in chicken embryonic retinal cells both in vivo and in vitro and represses Wnt-dependent specification of peripheral eye fates. Conversely, targeted inactivation of the TSK gene in mice causes expansion of the ciliary body and upregulation of Wnt2b and Fzd4 expression in the developing peripheral eye. Thus, we uncover a crucial role for TSK as a Wnt signaling inhibitor that regulates peripheral eye formation. eye development | signaling modulator | small leucine-rich proteoglycan

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“…5) (Liu et al, 2005; Bonilla-Claudio et al, 2012), while canonical Wnt signaling is detected throughout the proximal-distal axis of the mandibular arch (Fig. 6) (Mani et al, 2010). Hence, based solely on their expression, it is unclear whether these pathways interact in mandibular arch development.…”

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confidence: 99%

Inactivation of LAR family phosphatase genesPtprsandPtprfcauses craniofacial malformations resembling Pierre-Robin sequence

et al. 2013

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SUMMARYLeukocyte antigen related (LAR) family receptor protein tyrosine phosphatases (RPTPs) regulate the fine balance between tyrosine phosphorylation and dephosphorylation that is crucial for cell signaling during development and tissue homeostasis. Here we show that LAR RPTPs are required for normal development of the mandibular and maxillary regions. Approximately half of the mouse embryos lacking both Ptprs (RPTPσ) and Ptprf (LAR) exhibit micrognathia (small lower jaw), cleft palate and microglossia/glossoptosis (small and deep tongue), a phenotype closely resembling Pierre-Robin sequence in humans. We show that jaw bone and cartilage patterning occurs aberrantly in LAR family phosphatase-deficient embryos and that the mandibular arch harbors a marked decrease in cell proliferation. Analysis of signal transduction in embryonic tissues and mouse embryonic fibroblast cultures identifies an increase in Bmp-Smad signaling and an abrogation of canonical Wnt signaling associated with loss of the LAR family phosphatases. A reactivation of β-catenin signaling by chemical inhibition of GSK3β successfully resensitizes LAR family phosphatase-deficient cells to Wnt induction, indicating that RPTPs are necessary for normal Wnt/β-catenin pathway activation. Together these results identify LAR RPTPs as important regulators of craniofacial morphogenesis and provide insight into the etiology of Pierre-Robin sequence. Hendriks et al., 2013). LAR family phosphatases have been implicated in several key embryonic signaling pathways, including those involved in the negative regulation of growth factor receptors such as EGFR, RET and MET, and potentially modulate canonical Wnt/β-catenin signaling (Kypta et al., 1996;Müller et al., 1999;Tisi et al., 2000;Wang et al., 2000; Ensslen-Craig and BradyKalnay, 2004;Machide et al., 2006;Haapasalo et al., 2007;Uetani et al., 2009;Zheng et al., 2011). Although LAR family phosphatases are expressed in several embryonic and adult tissues (Schaapveld et al., 1998), mice mutant for single family members generally survive to adulthood, reflecting a functional redundancy within the family (Schaapveld et al., 1997; Elchebly et al., 1999;Wallace et al., 1999;Uetani et al., 2000;Thompson et al., 2003;Wang et al., 2011). Accordingly, Ptprd;Ptprs double-mutant embryos show defects in motoneuron innervation (Uetani et al., 2006), whereas Ptprs;Ptprf double-mutants harbor severe urogenital and craniofacial defects (Uetani et al., 2009). Although micrognathia and cleft palate were noted in approximately half of Ptprs;Ptprf double-knockout (DKO) embryos at embryonic day (E) 18.5 (Uetani et al., 2009), the molecular and cellular basis for this phenotype was not investigated further. In this study, we demonstrate that Ptprs and Ptprf are necessary for mandibular morphogenesis through the regulation of Wnt and Bmp signaling, and that their absence results in a phenotype closely resembling PRS. KEY WORDS: LAR phosphatases MATERIALS AND METHODS MiceThe derivation of genetically modified Ptprs;Ptprf mice has b...

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Visualizing canonical Wnt signaling during mouse craniofacial development

Cited by 67 publications

References 22 publications

Role of canonical Wnt signaling/β-catenin viaDermo1in cranial dermal cell development

Role of canonical Wnt signaling/β-catenin viaDermo1in cranial dermal cell development

Tsukushi functions as a Wnt signaling inhibitor by competing with Wnt2b for binding to transmembrane protein Frizzled4

Inactivation of LAR family phosphatase genesPtprsandPtprfcauses craniofacial malformations resembling Pierre-Robin sequence

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