Receptor‐regulated and inhibitory Smads are critical in regulating transforming growth factorβ–mediated Meckel's cartilage development

Ito, Yoshihiro; Bringas, Pablo; Mogharei, Ali; Zhao, Jingsong; Deng, Chu‐Xia; Chai, Yang

doi:10.1002/dvdy.10088

Cited by 70 publications

(74 citation statements)

References 51 publications

(68 reference statements)

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“…Mandibular development depends upon the interaction between the oral ectoderm and the CNC-derived mesenchyme within the first branchial arch. Within the oral ectoderm, signaling molecules, such as BMP, TGF-␤, and FGF, are expressed in a region-specific manner (Chai et al, 1994(Chai et al, , 1997Trumpp et al, 1999;Ito et al, 2002;Liu et al, 2005). They may regulate homeobox-containing genes (such as Dlx, Lhx, and Gsc) within the CNC-derived mesenchyme to generate early polarity and are responsible for patterning of the first branchial arch.…”

Section: Mandibular Morphogenesismentioning

confidence: 99%

Recent advances in craniofacial morphogenesis

Chai

Maxson

2006

Developmental Dynamics

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Craniofacial malformations are involved in three fourths of all congenital birth defects in humans, affecting the development of head, face, or neck. Tremendous progress in the study of craniofacial development has been made that places this field at the forefront of biomedical research. A concerted effort among evolutionary and developmental biologists, human geneticists, and tissue engineers has revealed important information on the molecular mechanisms that are crucial for the patterning and formation of craniofacial structures. Here, we highlight recent advances in our understanding of evo-devo as it relates to craniofacial morphogenesis, fate determination of cranial neural crest cells, and specific signaling pathways in regulating tissue-tissue interactions during patterning of craniofacial apparatus and the morphogenesis of tooth, mandible, and palate. Together, these findings will be beneficial for the understanding, treatment, and prevention of human congenital malformations and establish the foundation for craniofacial tissue regeneration. Developmental Dynamics 235:2353-2375, 2006.

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Section: Mandibular Morphogenesismentioning

confidence: 99%

Recent advances in craniofacial morphogenesis

Chai

Maxson

2006

Developmental Dynamics

Self Cite

535

503

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“…BMP-activated SMADs induce the expression of Runx2, which is indispensable for osteoblast differentiation (Ducy et al, 1997;Komori et al, 1997;Karsenty et al, 1999;Ducy, 2000) and mandibular osteogenesis (Otto et al, 1997). Furthermore, SMADs physically interact with RUNX2 to potentiate osteoblast-specific gene expression (Lee et al, 2000;Ito et al, 2002). Finally, other targets of BMP signaling, such as Msx1 (Suzuki et al, 1997;Tribulo et al, 2003), are required for proper epithelial-mesenchymal interactions in the mandible (Chen et al, 1996;Bei and Maas, 1998;Han et al, 2007) and affect skeletogenesis (Satokata and Maas, 1994).…”

Section: Introductionmentioning

confidence: 99%

Mesenchyme-dependent BMP signaling directs the timing of mandibular osteogenesis

et al. 2008

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To identify molecular and cellular mechanisms that determine when bone forms, and to elucidate the role played by osteogenic mesenchyme, we employed an avian chimeric system that draws upon the divergent embryonic maturation rates of quail and duck. Pre-migratory neural crest mesenchyme destined to form bone in the mandible was transplanted from quail to duck. In resulting chimeras, quail donor mesenchyme established significantly faster molecular and histological programs for osteogenesis within the relatively slower-progressing duck host environment. To understand this phenotype, we assayed for changes in the timing of epithelial-mesenchymal interactions required for bone formation and found that such interactions were accelerated in chimeras. In situ hybridization analyses uncovered donor-dependent changes in the spatiotemporal expression of genes, including the osteoinductive growth factor Bmp4. Mesenchymal expression of Bmp4 correlated with an ability of quail donor cells to form bone precociously without duck host epithelium, and also relied upon epithelial interactions until mesenchyme could form bone independently. Treating control mandibles with exogenous BMP4 recapitulated the capacity of chimeras to express molecular mediators of osteogenesis prematurely and led to the early differentiation of bone. Inhibiting BMP signaling delayed bone formation in a stage-dependent manner that was accelerated in chimeras. Thus, mandibular mesenchyme dictates when bone forms by temporally regulating its interactions with epithelium and its own expression of Bmp4. Our findings offer a developmental mechanism to explain how neural crest-derived mesenchyme and BMP signaling underlie the evolution of speciesspecific skeletal morphology.

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“…This suggests a model in which the combined effect of the misregulation of both pathways impairs cartilage formation in the mandible of Ptprs;Ptprf mutant embryos. As a result, bone formation, which requires Meckel's cartilage (Ito et al, 2002), would occur aberrantly (supplementary material Fig. S6).…”

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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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Receptor‐regulated and inhibitory Smads are critical in regulating transforming growth factorβ–mediated Meckel's cartilage development

Abstract: The proper development of Meckel's cartilage is critical for craniofacial skeletogenesis, because it serves as the primordium for the formation of mandible, malleus, incus, and sphenomandibular ligament.

Cited by 70 publications

References 51 publications

Recent advances in craniofacial morphogenesis

Recent advances in craniofacial morphogenesis

Mesenchyme-dependent BMP signaling directs the timing of mandibular osteogenesis

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

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