Extracellular Matrix in Secondary Palate Development

2019 ◽  
Vol 303 (6) ◽  
pp. 1543-1556 ◽  
Author(s):  
Shaun M. Logan ◽  
L. Bruno Ruest ◽  
M. Douglas Benson ◽  
Kathy K. H. Svoboda
Development ◽  
1988 ◽  
Vol 103 (Supplement) ◽  
pp. 41-60 ◽  
Author(s):  
Mark W. J. Ferguson

In all vertebrates, the secondary palate arises as bilateral outgrowths from the maxillary processes. In birds and most reptiles, these palatal shelves grow initially horizontally, but do not fuse with each other resulting in physiological cleft palate. In crocodilians, shelf fusion occurs resulting in an intact secondary palate. Mammalian palatal shelves initially grow vertically down the side of the tongue, but elevate at a precise time to a horizontal position above the dorsum of the tongue and fuse with each other to form an intact palate. Palatal shelf-elevation is the result of an intrinsic shelf elevating force, chiefly generated by the progressive accumulation and hydration of hyaluronic acid. In all vertebrates the nasal epithelium differentiates into pseudostratified ciliated columnar cells and the oral epithelia differentiates into stratified squamous cells, but the medial edge epithelial (MEE) phenotype differs in different groups. In mammals, the MEE of opposing shelves adhere to each other to form an epithelial seam which then disrupts by cell death and cell migration into the mesenchyme accompanied by an epitheliomesenchymal transformation. In birds, the MEE keratinize resulting in cleft palate whereas, in alligators, the MEE migrate onto the nasal aspect of the palate. In all vertebrates, this regional, temporal and species-specific epithelial differentiation is specified by the underlying mesenchyme. Signalling of this interaction is complex but involves both extracellular matrix and soluble factors e.g. minor collagen types, tenascin, EGF, TGFα, TGFβ, PDGF, FGF. These soluble growth factors have a biphasic effect: directly on the epithelia and on the mesenchyme where they stimulate or inhibit cell division and synthesis of specific extracellular matrix molecules. The extracellular matrix molecules (and bound growth factors) synthesized by the mesenchymal cells may then directly affect the epithelium. These signals cause differential gene expression via second messenger systems e.g. cAMP, cGMP, Ca2+, pH, pI etc. Molecular markers for nasal, medial and oral epithelial cell differentiation include the types of cytokeratin intermediate filaments and specific cell surface molecules recognized by monoclonal antibodies: the genes for such molecules are probably expressed in response to mesenchymal signals. Using such an approach, it is possible to go from a morphological description of palate development to a cellular analysis of the mechanisms involved and then to identification of candidate genes that may be important for screening and diagnosis of cleft palate.


Development ◽  
1976 ◽  
Vol 36 (2) ◽  
pp. 225-245
Author(s):  
Robert M. Greene ◽  
Robert M. Pratt

Research on development of the secondary palate has, in the past, dealt primarily with morphological aspects of shelf elevation and fusion. The many factors thought to be involved in palatal elevation, such as fetal neuromuscular activity and growth of the cranial base and mandible, as well as production of extracellular matrix and contractile elements in the palate, are mostly based on gross, light microscopic, morphometric or histochemical observations. Recently, more biochemical procedures have been utilized to describe palatal shelf elevation. Although these studies strongly suggest that palatal extracellular matrix plays a major role in shelf movement, interpretation of these data remains difficult owing to the complexity of tissue interactions involved in craniofacial development. Shelf elevation does not appear to involve a single motive factor, but rather a coordinated interaction of all of the abovementioned developmental events. Further analysis of mechanisms of shelf elevation requires development of new, and refinement of existing, in vitro procedures. A system that enables one to examine shelf elevation in vitro would allow more meaningful analysis of the relative importance of the various components in shelf movement. Much more is known about fusion of the palatal shelves, owing in large part to in vitro studies. Fusion of the apposing shelves, both in vivo and in vitro, is dependent upon adhesion and cell death of the midline epithelial cells. Adhesion between apposing epithelial surfaces appears to involve epithelial cell surface macromolecules. Further analysis of palatal epithelial adhesion should be directed towards characterization of those cell surface components responsible for this adhesive interaction. Midline epithelial cells cease DNA synthesis 24–36 h before shelf elevation and contact, become active in the synthesis of cell surface glycoproteins, and subsequently manifest morphological signs of necrosis. Death of the midline epithelial cells is thought to involve a programmed, lysosomal-mediated autolysis. Information regarding the appearance, distribution and quantitation of epithelial hydrolytic enzymes is needed. The control mechanisms which regulate adhesiveness and cell death in the palatal epithelium are not fully understood. Although palatal epithelial-mesenchymal recombination experiments have demonstrated a close relationship between the underlying mesenchyme and the differentiating epithelium, the molecular mechanism of interaction remains unclear. Recently cyclic nucleotides have been implicated as possible mediators of palatal epithelial differentiation. The developing secondary palate therefore offers a system whereby one can probe a variety of developmental phenomena. Cellular adhesion, programmed cell death and epithelial- mesenchymal interactions are all amenable to both morphological as well as bio- chemical analysis. Although research in the field of secondary palate development has been extensive, there still remain many provocative questions relating to normal development of this structure.


Development ◽  
1985 ◽  
Vol 88 (1) ◽  
pp. 265-279
Author(s):  
Robert F. Bulleit ◽  
Ernest F. Zimmerman

The intrinsic forces necessary for directing the reorientation of the secondary palate appear to reside in the anterior two thirds of the palate or presumptive hard palate. The hard palate could reorient regardless of whether it was intact or separated from the posterior third or presumptive soft palate. The soft palate could only reorient if the palate shelves are left intact. These intrinsic forces, within the hard palate, may be mediated by the mesenchymal cells, their extracellular matrix, or the epithelium surrounding the shelves. This latter possibly was tested by removing the epithelium, from either the presumptive oral or nasal surface followed by measurement of reorientation in vitro. Only after removal of the oral epithelium was a significant inhibition in reorientation observed. The treatment used to remove the epithelium, EDTA and scraping, was shown to remove 41 % of the oral epithelium leaving the majority of the basement membrane intact. The observed inhibition of reorientation did not appear to be a consequence of wound healing. Creation of wounds twice the area that was observed after treatment with EDTA and scraping inhibited reorientation minimally. These results suggest that the epithelium and particularly the anterior oral epithelium plays a major role in the reorientation of the murine secondary palate.


Development ◽  
1979 ◽  
Vol 50 (1) ◽  
pp. 145-154
Author(s):  
Alvaro A. Figueroa ◽  
Robert M. Pratt

The facial processes involved in primary palate formation undergo epithelial fusion in a manner morphologically analogous to that observed during secondary palate formation. We have used whole embryo culture to analyze the synthesis of macromolecules (DNA, protein, glycoprotein) in the primary palate, based on the incorporation of various labeled precursors. The results of this study demonstrate that changes in the synthesis of macromolecules occur during the fusion of the facial processes, which resemble those previously reported to occur during secondary palate development. These changes include cessation of DNA synthesis in cells in a restricted zone of the epithelium, concomitant with maintenance of glycoprotein synthesis. These findings indicate that the molecular events underlying the development of the primary and secondary palate may be similar.


2020 ◽  
pp. 105566562094377
Author(s):  
Katharina Freiberger ◽  
Shelby Hemker ◽  
Ryan McAnally ◽  
Rachel King ◽  
Vicki N. Meyers-Wallen ◽  
...  

Objective: To investigate the gestational timing of morphologic events in normal canine secondary palate development as a baseline for studies in dog models of isolated cleft palate (CP). Methods: Beagle and beagle/cocker spaniel-hybrid fetal dogs were obtained by cesarean-section on various days of gestation, timed from the initial rise of serum progesterone concentration. Morphology of fetal heads was determined by examining serial coronal sections. Results: On gestational day 35 (d35), the palatal shelves pointed ventrally alongside the tongue. On d36, palatal shelves were elongated and elevated to a horizontal position above the tongue but were not touching. On d37, palatine shelves and vomer were touching, but the medial epithelial seam (MES) between the apposed shelves remained. Immunostaining with epithelial protein markers showed that the MES gradually dissolved and was replaced by mesenchyme during d37-d44, and palate fusion was complete by d44. Examination of remnant MES suggested that fusion of palatal shelves began in mid-palate and moved rostrally and caudally. Conclusion: Palate development occurs in dogs in the steps described in humans and mice, but palate closure occurs at an intermediate time in gestation. These normative data will form the basis of future studies to determine pathophysiologic mechanisms in dog models of CP. Added clinical significance is the enhancement of dogs as a large animal model to test new approaches for palate repair, with the obvious advantage of achieving full maturity within 2 years rather than 2 decades.


1973 ◽  
Vol 52 (6) ◽  
pp. 1273-1280 ◽  
Author(s):  
Virginia M. Diewert

The course of the palatine arteries was studied in 96 rat fetuses. The descending palatine arteries were a major blood supply to the incisive area of the primary palate. When shelves were elevated, the arteries became positioned more medially and changed from a semicircular to a V-shaped form in the pre-maxilla.


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