Msx1 deficient mice exhibit cleft palate and abnormalities of craniofacial and tooth development

Satokata, Ichiro; Maas, Richard L.

doi:10.1038/ng0494-348

Cited by 1,173 publications

(907 citation statements)

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“…MSX1 and TGFB3 have emerged as candidate genes for oral cleft, based on expression studies 1,2 and animal models. 3,4 Their involvement is further supported by linkage and association studies in populations of different ethnic origin. [5][6][7][8] Although no deleterious mutation has been reported in TGFB3.…”

Section: Introductionmentioning

confidence: 83%

Contribution of MSX1 variants to the risk of non-syndromic cleft lip and palate in a Malay population

et al. 2011

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Oral clefts are clinically and genetically heterogeneous disorders that are influenced by both genetic and environmental factors. The present family-based association study investigated the role of the MSX1 and TGFB3 genes in the etiology of non-syndromic oral cleft in a Malay population. No transmission distortion was found in the transmission disequilibrium analysis for either MSX1-CA or TGFB3-CA intragenic markers, whereas TGFB3-CA exhibited a trend to excess maternal transmission. In sequencing the MSX1 coding regions in 124 patients with oral cleft, five variants were found, including three known variants (A34G, G110G and P147Q) and two novel variants (M37L and G267A). The P147Q and M37L variants were not observed in 200 control chromosomes, whereas G267A was found in one control sample, indicating a very rare polymorphic variant. Furthermore, the G110G variant displayed a significant association between patients with non-syndromic cleft lip, with or without cleft palate, and normal controls (P¼0.001, odds ratio¼2.241, 95% confidence interval, 1.357-3.700). Therefore, these genetic variants may contribute, along with other genetic and environmental factors, to this condition. INTRODUCTIONOral clefts are clinically and genetically heterogeneous disorders, involving both genetic and environmental factors. MSX1 and TGFB3 have emerged as candidate genes for oral cleft, based on expression studies 1,2 and animal models. 3,4 Their involvement is further supported by linkage and association studies in populations of different ethnic origin. [5][6][7][8] Although no deleterious mutation has been reported in TGFB3. 7,9 MSX1 has been suggested to function upstream of TGFB3 in the development of oral cleft. 10 The aim of the current research was to investigate the genetic association of MSX1 and TGFB3 in a Malay population with non-syndromic orofacial cleft. The association study was performed using intragenic CA markers for MSX1 and TGFB3. The coding regions of MSX1 were also directly sequenced.

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Section: Introductionmentioning

confidence: 83%

Contribution of MSX1 variants to the risk of non-syndromic cleft lip and palate in a Malay population

et al. 2011

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“…Furthermore, missense mutations and variants in the MSX1 gene have been associated with nonsyndromic CLP (Lidral et al, 1998;Jezewski et al, 2003). Although mice deficient in Msx1 have cleft palate but not CLP (Satokata and Maas, 1994), mice lacking both Msx1 and Msx2 gene function exhibit bilateral CLP (Y. Chai, personal communication). Msx1 and Msx2 likely play critical roles in facial mesenchymal proliferation, as Msx1 Ϫ/Ϫ mutant mice have shortened maxilla and mandibles as well as defects in palatal mesenchyme proliferation (Satokata and Maas, 1994;Zhang et al, 2002).…”

Section: The Bmp Pathwaymentioning

confidence: 99%

Development of the upper lip: Morphogenetic and molecular mechanisms

Jiang

Bush

Lidral

2005

Developmental Dynamics

288

304

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The vertebrate upper lip forms from initially freely projecting maxillary, medial nasal, and lateral nasal prominences at the rostral and lateral boundaries of the primitive oral cavity. These facial prominences arise during early embryogenesis from ventrally migrating neural crest cells in combination with the head ectoderm and mesoderm and undergo directed growth and expansion around the nasal pits to actively fuse with each other. Initial fusion is between lateral and medial nasal processes and is followed by fusion between maxillary and medial nasal processes. Fusion between these prominences involves active epithelial filopodial and adhering interactions as well as programmed cell death. Slight defects in growth and patterning of the facial mesenchyme or epithelial fusion result in cleft lip with or without cleft palate, the most common and disfiguring craniofacial birth defect. Recent studies of craniofacial development in animal models have identified components of several major signaling pathways, including Bmp, Fgf, Shh, and Wnt signaling, that are critical for proper midfacial morphogenesis and/or lip fusion. There is also accumulating evidence that these signaling pathways cross-regulate genetically as well as crosstalk intracellularly to control cell proliferation and tissue patterning. This review will summarize the current understanding of the basic morphogenetic processes and molecular mechanisms underlying upper lip development and discuss the complex interactions of the various signaling pathways and challenges for understanding cleft lip pathogenesis.

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“…Expression patterns of Msx1 were maintained in the underlying distal midline mesenchyme as were those of Msx2, eHAND, and dHAND. Notably, loss of Msx1 leads to the absence of those mandibular midline structures that persist in the Fgf8 Nes-CreϪ/Ϫ mice-namely, the rostral process and incisors (Satokata and Maas, 1994;Houzelstein et al, 1997). Although at E9.5 the Fgf8-inducible genes Dlx2 and Dlx5 were expressed in BA1, it is not clear that their expression was indeed Fgf8-dependent: Dlx2 is expressed in migrating CNC cells before their exposure to BA1 localized Fgf8 and Dlx2 and Dlx5 are also Bmp-which is expressed at the distal midlineinducible (Neubuser et al, 1997;Bei and Maas, 1998;Thomas et al, 1997Thomas et al, , 2000Tucker et al, 1999a,b;Mina et al, 2002).…”

Section: Figmentioning

confidence: 99%

21^st Century neontology and the comparative development of the vertebrate skull

Depew

Simpson

2006

Developmental Dynamics

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Classic neontology (comparative embryology and anatomy), through the application of the concept of homology, has demonstrated that the development of the gnathostome (jawed vertebrate) skull is characterized both by a fidelity to the gnathostome bauplan and the exquisite elaboration of final structural design. Just as homology is an old concept amended for modern purposes, so are many of the questions regarding the development of the skull. With due deference to Geoffroy-St. Hilaire, Cuvier, Owen, Lankester et al., we are still asking: How are bauplan fidelity and elaboration of design maintained, coordinated, and modified to generate the amazing diversity seen in cranial morphologies? What establishes and maintains pattern in the skull? Are there universal developmental mechanisms underlying gnathostome autapomorphic structural traits? Can we detect and identify the etiologies of heterotopic (change in the topology of a developmental event), heterochronic (change in the timing of a developmental event), and heterofacient (change in the active capacetence, or the elaboration of capacity, of a developmental event) changes in craniofacial development within and between taxa? To address whether jaws are all made in a like manner (and if not, then how not), one needs a starting point for the sake of comparison. To this end, we present here a "hinge and caps" model that places the articulation, and subsequently the polarity and modularity, of the upper and lower jaws in the context of cranial neural crest competence to respond to positionally located epithelial signals. This model expands on an evolving model of polarity within the mandibular arch and seeks to explain a developmental patterning system that apparently keeps gnathostome jaws in functional registration yet tractable to potential changes in functional demands over time. It relies upon a system for the establishment of positional information where pattern and placement of the "hinge" is driven by factors common to the junction of the maxillary and mandibular branches of the first arch and of the "caps" by the signals emanating from the distal-most first arch midline and the lamboidal junction (where the maxillary branch meets the frontonasal processes). In this particular model, the functional registration of jaws is achieved by the integration of "hinge" and "caps" signaling, with the "caps" sharing at some critical level a developmental history that potentiates their own coordination. We examine the evidential foundation for this model in mice, examine the robustness with which it can be applied to other taxa, and examine potential proximate sources of the signaling centers. Lastly, as developmental biologists have long held that the anterior-most mesendoderm (anterior archenteron roof or prechordal plate) is in some way integral to the normal formation of the head, including the cranial skeletal midlines, we review evidence that the seminal patterning influences on the early anterior ectoderm extend well beyond the neural plate and are just as importan...

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Msx1 deficient mice exhibit cleft palate and abnormalities of craniofacial and tooth development

Cited by 1,173 publications

References 46 publications

Contribution of MSX1 variants to the risk of non-syndromic cleft lip and palate in a Malay population

Contribution of MSX1 variants to the risk of non-syndromic cleft lip and palate in a Malay population

Development of the upper lip: Morphogenetic and molecular mechanisms

21^st Century neontology and the comparative development of the vertebrate skull

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Msx1 deficient mice exhibit cleft palate and abnormalities of craniofacial and tooth development

Cited by 1,173 publications

References 46 publications

Contribution of MSX1 variants to the risk of non-syndromic cleft lip and palate in a Malay population

Contribution of MSX1 variants to the risk of non-syndromic cleft lip and palate in a Malay population

Development of the upper lip: Morphogenetic and molecular mechanisms

21st Century neontology and the comparative development of the vertebrate skull

Contact Info

Product

Resources

About

21^st Century neontology and the comparative development of the vertebrate skull