Fate-mapping of the epithelial seam during palatal fusion rules out epithelial–mesenchymal transformation

527

503

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.

Section: Orofacial Ectodermmentioning

confidence: 99%

Recent advances in craniofacial morphogenesis

Chai

Maxson

2006

527

503

“…There is strong evidence that disruption of the palatal epithelial seam during palatal fusion results at least in part from apoptosis (Cecconi et al, 1998;Cuervo and Covarrubias, 2004;Martinez-Alvarez et al, 2004;Vaziri Sani et al, 2005). We carried out terminal deoxynucleotidyl transferasemediated deoxyuridinetriphosphate nick end-labeling (TUNEL) analysis to investigate the mechanism involved in the disruption of the epithelial seam between the palate and tongue in the Jag2 ⌬DSL/⌬DSL mutants and found that the palate-tongue seam contained numerous apoptotic cells, similar to the wild-type palate-palate seam during palatal fusion (Fig.…”

Section: Analysis Of Jag2 Mutants Provides Support For the Role Of Tgmentioning

confidence: 99%

“…Tgf␤3 has been proposed to induce epithelial-mesenchymal transformation of the palatal MEE (Kaartinen et al, 1997;Sun et al, 1998;reviewed in Nawshad et al, 2004). However, recent fate mapping of the mouse palatal MEE cells using the Cre/loxP-mediated in vivo lineage tracing method has ruled out MEE contribution to the palatal mesenchyme (Vaziri Sani et al, 2005). On the other hand, the fusing palatal epithelial seam cells have been shown to undergo apoptosis both in vivo and in vitro (Cuervo and Covarrubias, 2004;Vaziri Sani et al, 2005).…”

Section: Molecular and Cellular Mechanisms Underlying The Aberrant Ormentioning

confidence: 99%

“…However, recent fate mapping of the mouse palatal MEE cells using the Cre/loxP-mediated in vivo lineage tracing method has ruled out MEE contribution to the palatal mesenchyme (Vaziri Sani et al, 2005). On the other hand, the fusing palatal epithelial seam cells have been shown to undergo apoptosis both in vivo and in vitro (Cuervo and Covarrubias, 2004;Vaziri Sani et al, 2005). Tgf␤3 has been shown to promote apoptosis in other developmental processes (Nguyen and Pollard, 2000;Opperman et al, 2000;Dunker et al, 2002).…”

Section: Molecular and Cellular Mechanisms Underlying The Aberrant Ormentioning

confidence: 99%

See 1 more Smart Citation

Jag2‐Notch1 signaling regulates oral epithelial differentiation and palate development

Casey

Lan

Cho

et al. 2006

122

During mammalian palatogenesis, palatal shelves initially grow vertically from the medial sides of the paired maxillary processes flanking the developing tongue and subsequently elevate and fuse with each other above the tongue to form the intact secondary palate. Pathological palate-mandible or palate-tongue fusions have been reported in humans and other mammals, but the molecular and cellular mechanisms that prevent such aberrant adhesions during normal palate development are unknown. We previously reported that mice deficient in Jag2, which encodes a cell surface ligand for the Notch family receptors, have cleft palate associated with palate-tongue fusions. In this report, we show that Jag2 is expressed throughout the oral epithelium and is required for Notch1 activation during oral epithelial differentiation. We show that Notch1 is normally highly activated in the differentiating oral periderm cells covering the developing tongue and the lateral oral surfaces of the mandibular and maxillary processes during palate development. Oral periderm activation of Notch1 is significantly attenuated during palate development in the Jag2 mutants. Further molecular and ultrastructural analyses indicate that oral epithelial organization and periderm differentiation are disrupted in the Jag2 mutants. Moreover, we show that the Jag2 mutant tongue fused to wild-type palatal shelves in recombinant explant cultures. These data indicate that Jag2-Notch1 signaling is spatiotemporally regulated in the oral epithelia during palate development to prevent premature palatal shelf adhesion to other oral tissues and to facilitate normal adhesion between the elevated palatal shelves.

“…The confusion may have arisen due in part to species differences (e.g., chick vs. mouse and human) in facial morphogenesis and in part to lack of synthesis of the fragmentary and often incomplete information gained from individual studies. Moreover, whereas it has been widely accepted that epithelial-mesenchymal transformation (EMT) of the epithelial seam is the major mechanism for both lip and palate fusion (Fitchett and Hay, 1989;Shuler et al, 1991Shuler et al, , 1992Griffith and Hay, 1992;Hay, 1995Hay, , 2005Sun et al, 2000;Cox, 2004;Nawshad et al, 2004), recent studies have challenged this theory and demonstrated that the palatal epithelial seam gradually regresses by programmed cell death rather than by EMT (Cuervo and Covarrubias, 2004;Vaziri Sani et al, 2005). At the molecular level, recent studies in chick and mice have identified specific roles for several major signaling pathways, including Bmp, Fgf, and Shh signaling pathways in midfacial morphogenesis (Hu and Helms, 1999;Trumpp et al, 1999;Ashique et al, 2002;Trokovic et al, 2003;Jeong et al, 2004;Liu et al, 2005b).…”

Section: Introductionmentioning

confidence: 99%

Development of the upper lip: Morphogenetic and molecular mechanisms

Jiang

Bush

Lidral

2005

277

304

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.