Talk:Palate Development

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Note - This sub-heading shows an automated computer PubMed search using the listed sub-heading term. References appear in this list based upon the date of the actual page viewing. Therefore the list of references do not reflect any editorial selection of material based on content or relevance. In comparison, references listed on the content page and discussion page (under the publication year sub-headings) do include editorial selection based upon relevance and availability. (More? Pubmed Most Recent)

Palate Development

<pubmed limit=10>Palate+Development</pubmed>

Cleft Palate

<pubmed limit=10>Cleft+Palate</pubmed>

Regulation of the Epithelial Adhesion Molecule CEACAM1 Is Important for Palate Formation

PLoS One. 2013 Apr 17;8(4):e61653. doi: 10.1371/journal.pone.0061653. Print 2013.

Mima J, Koshino A, Oka K, Uchida H, Hieda Y, Nohara K, Kogo M, Chai Y, Sakai T. Source Department of Oral-facial Disorders, Osaka University Graduate School of Dentistry, Suita, Osaka, Japan ; First Department of Oral and Maxillofacial Surgery, Osaka University Graduate School of Dentistry, Suita, Osaka, Japan. Abstract Cleft palate results from a mixture of genetic and environmental factors and occurs when the bilateral palatal shelves fail to fuse. The objective of this study was to search for new genes involved in mouse palate formation. Gene expression of murine embryonic palatal tissue was analyzed at various developmental stages before, during, and after palate fusion using GeneChip® microarrays. Ceacam1 was one of the highly up-regulated genes during palate formation, and this was confirmed by quantitative real-time PCR. Immunohistochemical staining showed that CEACAM1 was present in prefusion palatal epithelium and was degraded during fusion. To investigate the developmental role of CEACAM1, function-blocking antibody was added to embryonic mouse palate in organ culture. Palatal fusion was inhibited by this function-blocking antibody. To investigate the subsequent developmental role of CEACAM1, we characterized Ceacam1-deficient (Ceacam1 (-/-)) mice. Epithelial cells persisted abnormally at the midline of the embryonic palate even on day E16.0, and palatal fusion was delayed in Ceacam1 (-/-) mice. TGFβ3 expression, apoptosis, and cell proliferation in palatal epithelium were not affected in the palate of Ceacam1(-/-)mice. However, CEACAM1 expression was retained in the remaining MEE of TGFβ-deficient mice. These results suggest that CEACAM1 has roles in the initiation of palatal fusion via epithelial cell adhesion.

PMID 23613893

2011

Tmem26 is dynamically expressed during palate and limb development but is not required for embryonic survival

PLoS One. 2011;6(9):e25228. Epub 2011 Sep 29. Town L, McGlinn E, Davidson TL, Browne CM, Chawengsaksophak K, Koopman P, Richman JM, Wicking C. Source Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia.

Abstract

The Tmem26 gene encodes a novel protein that we have previously shown to be regulated by hedgehog signalling in the mouse limb. We now report that Tmem26 expression is spatially and temporally restricted in other regions of the mouse embryo, most notably the facial primordia. In particular, Tmem26 expression in the mesenchyme of the maxillary and nasal prominences is coincident with fusion of the primary palate. In the secondary palate, Tmem26 is expressed in the palatal shelves during their growth and fusion but is downregulated once fusion is complete. Expression was also detected at the midline of the expanding mandible and at the tips of the eyelids as they migrate across the cornea. Given the spatio-temporally restricted expression of Tmem26, we sought to uncover a functional role in embryonic development through targeted gene inactivation in the mouse. However, ubiquitous inactivation of Tmem26 led to no overt phenotype in the resulting embryos or adult mice, suggesting that TMEM26 function is dispensable for embryonic survival.

PMID 21980401

Role of GSK-3β in the Osteogenic Differentiation of Palatal Mesenchyme

PLoS One. 2011;6(10):e25847. Epub 2011 Oct 14.

Nelson ER, Levi B, Sorkin M, James AW, Liu KJ, Quarto N, Longaker MT. Source Hagey Laboratory for Pediatric Regenerative Medicine, Plastic and Reconstructive Surgery Division, Department of Surgery, Stanford University School of Medicine, Stanford, California, United States of America.

Abstract

INTRODUCTION: The function of Glycogen Synthase Kinases 3β (GSK-3β) has previously been shown to be necessary for normal secondary palate development. Using GSK-3ß null mouse embryos, we examine the potential coordinate roles of Wnt and Hedgehog signaling on palatal ossification.

METHODS: Palates were harvested from GSK-3β, embryonic days 15.0-18.5 (e15.0-e18.5), and e15.5 Indian Hedgehog (Ihh) null embryos, and their wild-type littermates. The phenotype of GSK-3β null embryos was analyzed with skeletal whole mount and pentachrome stains. Spatiotemporal regulation of osteogenic gene expression, in addition to Wnt and Hedgehog signaling activity, were examined in vivo on GSK-3β and Ihh +/+ and -/- e15.5 embryos using in situ hybridization and immunohistochemistry. To corroborate these results, expression of the same molecular targets were assessed by qRT-PCR of e15.5 palates, or e13.5 palate cultures treated with both Wnt and Hedgehog agonists and anatagonists.

RESULTS: GSK-3β null embryos displayed a 48 percent decrease (*p<0.05) in palatine bone formation compared to wild-type littermates. GSK-3β null embryos also exhibited decreased osteogenic gene expression that was associated with increased Wnt and decreased Hedgehog signaling. e13.5 palate culture studies demonstrated that Wnt signaling negatively regulates both osteogenic gene expression and Hedgehog signaling activity, while inhibition of Wnt signaling augments both osteogenic gene expression and Hedgehog signaling activity. In addition, no differences in Wnt signaling activity were noted in Ihh null embryos, suggesting that canonical Wnt may be upstream of Hedgehog in secondary palate development. Lastly, we found that GSK-3β -/- palate cultures were "rescued" with the Wnt inhibitor, Dkk-1.

CONCLUSIONS: Here, we identify a critical role for GSK-3β in palatogenesis through its direct regulation of canonical Wnt signaling. These findings shed light on critical developmental pathways involved in palatogenesis and may lead to novel molecular targets to prevent cleft palate formation.

PMID 22022457 [PubMed - in process] PMCID: PMC3194817

Histomorphological study of palatal shelf elevation during murine secondary palate formation

Dev Dyn. 2011 May 26. doi: 10.1002/dvdy.22670. Yu K, Ornitz DM. Source Department of Developmental Biology, Washington University School of Medicine, St. Louis, Missouri. kyu@wustl.edu; dornitz@wustl.edu.

Abstract

During mammalian secondary palate development, the palatal shelves undergo dramatic morphological changes to elevate from a vertical to a horizontal plane in the oral-nasal cavity. We found that E14.5 mouse embryos displayed marked variations in shelf morphology that represent various intermediate states of the elevation process. With these variations, we reconstructed the sequence of shelf morphological changes that take place during the elevation process and discovered distinct patterns in different regions along the anterior-posterior (AP) axis. Moreover, our study revealed that during the elevation process, shelf morphological changes are accompanied by tongue morphological changes, which also show distinct characteristics along the AP axis. We further discuss how to divide the palate along the AP axis based on morphological criteria. Our study provides a framework that recognizes variation in timing of palatal morphogenesis along the AP axis that will aid in the investigation of the mechanisms regulating palatal shelf elevation. Developmental Dynamics, 2011. © 2011 Wiley-Liss, Inc.

Copyright © 2011 Wiley-Liss, Inc.

• In mammals, after bulging out bilaterally from the maxillary process, the palate shelves grow rapidly away from the maxilla along the side of the tongue.
• Formation of the secondary palate requires the palatal shelves to undergo a process called shelf elevation or shelf reorientation
• palate shelves move from lateral of the tongue to above the dorsum of the tongue and change their orientation in the oral-nasal cavity from vertical to horizontal.
• the opposing horizontal shelves contact each other at the midline of the oral-nasal cavity
• A midline epithelial seam (MES) is then formed by fusion of the medial edge epithelia (MEE) of the opposing palatal shelves.

Tongue changes during shelf elevation

• displacement between the root of tongue and the extreme posterior end of the palate
• tongue movement likely due to growth of the mandible (or Meckel's cartilage) in the lower jaw to which the root of the tongue is attached.
• tongue expands laterally in the oral cavity
  • increases the dorsal width of the tongue along the medial-lateral (ML) axis
  • reduces tongue height along the dorsal-ventral (DV) axis.
• tongue flattening - could result from tongue lateral expansion, which actually occurs throughout the entire palate

PMID: 21618642 http://www.ncbi.nlm.nih.gov/pubmed/21618642

http://onlinelibrary.wiley.com/doi/10.1002/dvdy.22670/abstract

Ephrin reverse signaling controls palate fusion via a PI3 kinase-dependent mechanism

Dev Dyn. 2011 Feb;240(2):357-64. doi: 10.1002/dvdy.22546.

San Miguel S, Serrano MJ, Sachar A, Henkemeyer M, Svoboda KK, Benson MD.

Department of Biomedical Sciences, Texas A&M Health Science Center Baylor College of Dentistry, Dallas, Texas. Abstract

Secondary palate fusion requires adhesion and epithelial-to-mesenchymal transition (EMT) of the epithelial layers on opposing palatal shelves. This EMT requires transforming growth factor β3 (TGFβ3), and its failure results in cleft palate. Ephrins, and their receptors, the Ephs, are responsible for migration, adhesion, and midline closure events throughout development. Ephrins can also act as signal-transducing receptors in these processes, with the Ephs serving as ligands (termed "reverse" signaling). We found that activation of ephrin reverse signaling in chicken palates induced fusion in the absence of TGFβ3, and that PI3K inhibition abrogated this effect. Further, blockage of reverse signaling inhibited TGFβ3-induced fusion in the chicken and natural fusion in the mouse. Thus, ephrin reverse signaling is necessary and sufficient to induce palate fusion independent of TGFβ3. These data describe both a novel role for ephrins in palate morphogenesis, and a previously unknown mechanism of ephrin signaling. Developmental Dynamics 240:357-364, 2011. © 2011 Wiley-Liss, Inc.

Copyright © 2011 Wiley-Liss, Inc.

PMID: 21246652 http://www.ncbi.nlm.nih.gov/pubmed/21246652

2010

The origin and early development of the nasal septum in human embryos

Ann Anat. 2010 Apr 20;192(2):82-5. Epub 2010 Jan 25. Steding G, Jian Y. Source Centre of Anatomy, Georg August University Goettingen, Kreuzbergring 36, 37075 Goettingen, Germany.

Abstract

Based on scanning electron microscopic dissections of human embryos and fetuses of the sixth to the twelfth week (Carnegie stages 16-23 and early fetus), the origin of the nasal septum was studied. The findings show that the nasal septum does not grow downwards. It is derived from the tissue between the primary choanae: as such, its anlage is present from the very beginning. Its contact and fusion with the palatal shelves is made possible by the elevation of the palatal shelves from the vertical into the horizontal position, as the tongue descends. Copyright 2010 Elsevier GmbH. All rights reserved.

PMID 20149609

Incidence of cleft Lip and palate in the state of Andhra Pradesh, South India

Indian J Plast Surg. 2010 Jul;43(2):184-9.

Reddy SG, Reddy RR, Bronkhorst EM, Prasad R, Ettema AM, Sailer HF, Bergé SJ.

SourceGSR Institute of Craniofacial Surgery, Hyderabad, Andhra Pradesh, India.

Abstract OBJECTIVE:To assess the incidence of cleft lip and palate defects in the state of Andhra Pradesh, India.DESIGN SETTING:The study was conducted in 2001 in the state of Andhra Pradesh, India. The state has a population of 76 million. Three districts, Cuddapah, Medak and Krishna, were identified for this study owing to their diversity. They were urban, semi-urban and rural, respectively. Literacy rates and consanguinity of the parents was elicited and was compared to national averages to find correlations to cleft births. Type and side of cleft were recorded to compare with other studies around the world and other parts of India.RESULTS:The birth rate of clefts was found to be 1.09 for every 1000 live births. This study found that 65% of the children born with clefts were males. The distribution of the type of cleft showed 33% had CL, 64% had CLP, 2% had CP and 1% had rare craniofacial clefts. Unilateral cleft lips were found in 79% of the patients. Of the unilateral cleft lips 64% were left sided. There was a significant correlation of children with clefts being born to parents who shared a consanguineous relationship and those who were illiterate with the odds ratio between 5.25 and 7.21 for consanguinity and between 1.55 and 5.85 for illiteracy, respectively.CONCLUSION:The birth rate of clefts was found to be comparable with other Asian studies, but lower than found in other studies in Caucasian populations and higher than in African populations. The incidence was found to be similar to other studies done in other parts of India. The distribution over the various types of cleft was comparable to that found in other studies.

PMID 21217978

Epidemiologic factors causing cleft lip and palate and their regularities of occurrence in Estonia

Stomatologija. 2010;12(4):105-108.

Jagomagi T, Soots M, Saag M.

Department of Stomatology, Faculty of Medicine, University of Tartu, Kastani 16, Tartu 50410, Estonia. triin.jagomagi@ortodontia.ee.

Abstract OBJECTIVES. To study epidemiological factors causing development of cleft lip and palate and their occurrence regularities. MATERIALS AND METHODS. This study included 583 cleft lip and palate patients and the information for statistical analyses was gathered from Tartu University Hospital. RESULTS. 19% of the patients had a cleft lip (CL), 39% of the patients had a cleft palate (CP), and 42 % of the patients had a cleft lip and palate (CLP). The ratio for different cleft types CL: CLP: CP was 1:2:2. In unilateral CLP and CL cases, the left side was affected 2.2 times more frequently than the right side. Boys had a CLP nearly 2.1 times more often than girls. CP was more common for girls (60%) than for boys (40%). 30% of children had multiple malformations. 2.6% of children with clefts were born premature, half of which had accompanying developmental anomalies. The average birth weight for cleft child was ~ 3400 grams. 6.8% of children with clefts had a birth weight below 2.5 kg. In case of children with clefts, the mother's age exceeded 30 years in 1/4 of cases and father's age in 1/3 of cases. Both parents were older than 30 years in 66% of the cases. 1/5 of both parents were older than 30 years. 1/3 of mothers of children with clefts had suffered psychological stress, 1/5 of mothers had done hard physical work. 1/5 of mothers had an exposure to teratogenic toxic substances. 15% of them received medications during the first trimester of pregnancy. 15% of mothers had experienced hormonal disorders. CONCLUSIONS. As a result of the study we found a high occurrence rate of CP (CL: CLP: CP - 1:2:2), which is similar to the studies conducted in Finland and Sweden. The reasons for this ratio need further research.

PMID: 21266834 http://www.ncbi.nlm.nih.gov/pubmed/21266834

A genome-wide association study of cleft lip with and without cleft palate identifies risk variants near MAFB and ABCA4

Nat Genet. 2010 Jun;42(6):525-9. Epub 2010 May 2.

Beaty TH, Murray JC, Marazita ML, Munger RG, Ruczinski I, Hetmanski JB, Liang KY, Wu T, Murray T, Fallin MD, Redett RA, Raymond G, Schwender H, Jin SC, Cooper ME, Dunnwald M, Mansilla MA, Leslie E, Bullard S, Lidral AC, Moreno LM, Menezes R, Vieira AR, Petrin A, Wilcox AJ, Lie RT, Jabs EW, Wu-Chou YH, Chen PK, Wang H, Ye X, Huang S, Yeow V, Chong SS, Jee SH, Shi B, Christensen K, Melbye M, Doheny KF, Pugh EW, Ling H, Castilla EE, Czeizel AE, Ma L, Field LL, Brody L, Pangilinan F, Mills JL, Molloy AM, Kirke PN, Scott JM, Arcos-Burgos M, Scott AF.

Johns Hopkins University, School of Public Health, Baltimore, Maryland, USA. tbeaty@jhsph.edu Erratum in:

Nat Genet. 2010 Aug;42(8):727. Scott, James M [corrected to Scott, John M]. Abstract Case-parent trios were used in a genome-wide association study of cleft lip with and without cleft palate. SNPs near two genes not previously associated with cleft lip with and without cleft palate (MAFB, most significant SNP rs13041247, with odds ratio (OR) per minor allele = 0.704, 95% CI 0.635-0.778, P = 1.44 x 10(-11); and ABCA4, most significant SNP rs560426, with OR = 1.432, 95% CI 1.292-1.587, P = 5.01 x 10(-12)) and two previously identified regions (at chromosome 8q24 and IRF6) attained genome-wide significance. Stratifying trios into European and Asian ancestry groups revealed differences in statistical significance, although estimated effect sizes remained similar. Replication studies from several populations showed confirming evidence, with families of European ancestry giving stronger evidence for markers in 8q24, whereas Asian families showed stronger evidence for association with MAFB and ABCA4. Expression studies support a role for MAFB in palatal development.

PMID: 20436469 http://www.ncbi.nlm.nih.gov/pubmed/20436469

Matrix metalloproteinase-25 has a functional role in mouse secondary palate development and is a downstream target of TGF-β3

BMC Dev Biol. 2010 Sep 1;10:93.

Brown GD, Nazarali AJ.

Laboratory of Molecular Biology, College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, Saskatchewan S7N 5C9, Canada. Abstract BACKGROUND: Development of the secondary palate (SP) is a complex event and abnormalities during SP development can lead to cleft palate, one of the most common birth disorders. Matrix metalloproteinases (MMPs) are required for proper SP development, although a functional role for any one MMP in SP development remains unknown. MMP-25 may have a functional role in SP formation as genetic scans of the DNA of human cleft palate patients indicate a common mutation at a region upstream of the MMP-25 gene. We report on the gene expression profile of MMP-25 in the developing mouse SP and identify its functional role in mouse SP development.

RESULTS: MMP-25 mRNA and protein are found at all SP developmental stages in mice, with the highest expression at embryonic day (E) 13.5. Immunohistochemistry and in situ hybridization localize MMP-25 protein and mRNA, respectively, to the apical palate shelf epithelial cells and apical mesenchyme. MMP-25 knockdown with siRNA in palatal cultures results in a significant decrease in palate shelf fusion and persistence of the medial edge epithelium. MMP-25 mRNA and protein levels significantly decrease when cultured palate shelves are incubated in growth medium with 5 μg/mL of a TGF-β3-neutralizing antibody.

CONCLUSIONS: Our findings indicate: (i) MMP-25 gene expression is highest at E12.5 and E13.5, which corresponds with increasing palate shelf growth downward alongside the tongue; (ii) MMP-25 protein and mRNA expression predominantly localize in the apical epithelium of the palate shelves, but are also found in apical areas of the mesenchyme; (iii) knockdown of MMP-25 mRNA expression impairs palate shelf fusion and results in significant medial edge epithelium remaining in contacted areas; and (iv) bio-neutralization of TGF-β3 significantly decreases MMP-25 gene expression. These data suggest a functional role for MMP-25 in mouse SP development and are the first to identify a role for a single MMP in mouse SP development.

PMID: 20809987

Antenatal determinants of oro-facial clefts in Southern Nigeria

Afr Health Sci. 2010 Mar;10(1):31-9.

Omo-Aghoja VW, Omo-Aghoja LO, Ugboko VI, Obuekwe ON, Saheeb BD, Feyi-Waboso P, Onowhakpor A.

Department of Oral and Maxillofacial Surgery, Central Hospital, Sapele, Nigeria. Abstract OBJECTIVES: Cleft lip with or without cleft palate, is the most common serious congenital anomaly that affects the orofacial regions. The management and care of the cleft patient constitutes a substantial proportion of the workload of the Nigerian maxillofacial surgeon and allied specialties. Yet, there are no specific programmes targeted at this group. We believe that the findings of this study is capable of identifying useful interventions for designing programs that will lead to a reduction in the burden of orofacial cleft in Nigeria.

METHODS: It was a transverse cross-sectional study that was undertaken at the Maxillofacial Units of the University of Benin Teaching Hospital and the Central Hospital, Benin City respectively. The prevalence and antenatal determinants of cleft lip and palate were determined.

RESULTS: Cleft lip and palate were often encountered in clinical practice in Benin City with a prevalence of 1.35%. The results showed that orofacial clefts were commoner in females and that the combined unilateral cleft lip and palate was the commonest entity encountered amongst the cases. The following risk factors were associated with the risk of development of cleft lip and palate: Paternal age >40 years, maternal age >35 years, genetic/family history, low socio-economic status, alcohol consumption and indulgence in the intake of herbal medications in pregnancy.

CONCLUSION: Public health education programmes and advocacy activities geared towards raising awareness of the identified risk factors for the development of cleft lip and or cleft palate would go a long way to obviate the occurrence and reduce the burden.

PMID: 20811522

2009

Internet-derived information on cleft lip and palate for families with affected children

Cleft Palate Craniofac J. 2009 Jan;46(1):75-80. Epub 2008 May 21. Antonarakis GS, Kiliaridis S. Source Department of Orthodontics, Dental School, University of Geneva, Switzerland. Gregory.Antonarakis@medicine.unige.ch

Abstract

OBJECTIVE: To investigate the nature and readability of cleft lip and palate-related family information on the Internet. MATERIALS AND METHODS: An Internet search for "cleft lip," "cleft palate," and "family information" was carried out using three search engines. Within each search, the first 25 relevant websites identified were downloaded and assessed for country of origin, authorship, domain, referencing, links, advertising, mention of orthodontics, illustrations, cleft-specificity, and content. Readability was determined using the Flesch Reading Ease Score, the Flesch-Kincaid Grade Level, and the Fog Scale Level. Data were analyzed by simple descriptive statistics. RESULTS: The initial search returned in excess of 1,800,000 hits. A total of 49 websites were evaluated, excluding repetitions, with a wide range of information available. The websites assessed were mostly of U.S. origin, with a .org domain, authored by universities/hospitals, not cleft-specific, without advertisements, contained links but not references, mentioned orthodontics even if to a small extent, contained some form of illustrations, and varied greatly in quantity and quality of information presented. A wide range of readability scores was obtained, equating to reading ages from fourth grade to university graduate level, with a mean reading age at the eighth to ninth grade level. CONCLUSIONS: Cleft lip and palate-related information for families on the Internet is variable in content, quality, and readability. Clinicians should have the responsibility to guide and help parents with website retrieval, while authors of websites should aim to keep information readable and relevant to family demands.

PMID 19115798

One-stage palate repair improves speech outcome and early maxillary growth in patients with cleft lip and palate

J Physiol Pharmacol. 2009 Dec;60 Suppl 8:37-41.

Pradel W, Senf D, Mai R, Ludicke G, Eckelt U, Lauer G.

Department of Oral and Maxillofacial Surgery, University Hospital Carl Gustav Carus, Dresden Technical University, Dresden, Germany. winnie.pradel@uniklinikum-dresden.de Abstract There are several types of palatal surgery; each cleft centre chooses its own technique based on experience and treatment philosophy. The aim of this study was to compare speech outcome and maxillary growth in children with cleft lip and palate deformity after palate repair with either a one-stage or a two- stage procedure and to identify the better treatment protocol. In 24 children, speech outcome was assessed regarding resonance, nasal escape, compensatory articulations, facial grimace, and spontaneous speech. In addition, plaster models of 15 children were compared. In 12 children, a two-stage procedure was performed (group A): at the age of 9-12 months, an intravelar veloplasty for repair of the soft palate, and at the age of 24-36 months a bipedicled flap closure of the hard palate. In 12 children, the same techniques were used in a one-stage procedure, at the age of 9-12 months (group B). The children of group B showed less altered resonance and less nasal emission at 4 years of age compared to the children of group A. At 6 years, the children of group A had improved their speech skills, but they did not equal the results of group B. In the study models of group A at age 6 years, the transverse dimension (anterior and posterior width of the dental arch) was smaller than in the models of group B. The one-stage repair of cleft palate at the age of 9-12 months seems to have a more positive influence on speech development and early maxillary growth than the two-stage procedure.

PMID: 20400790 http://www.ncbi.nlm.nih.gov/pubmed/20400790

2007

A dosage-dependent role for Spry2 in growth and patterning during palate development

Mech Dev. 2007 Sep-Oct;124(9-10):746-61. Epub 2007 Jul 10.

Welsh IC, Hagge-Greenberg A, O'Brien TP.

Department of Biomedical Sciences, Cornell University, Ithaca, NY 14853, USA.

Abstract The formation of the palate involves the coordinated outgrowth, elevation and midline fusion of bilateral shelves leading to the separation of the oral and nasal cavities. Reciprocal signaling between adjacent fields of epithelial and mesenchymal cells directs palatal shelf growth and morphogenesis. Loss of function mutations in genes encoding FGF ligands and receptors have demonstrated a critical role for FGF signaling in mediating these epithelial-mesenchymal interactions. The Sprouty family of genes encode modulators of FGF signaling. We have established that mice carrying a deletion that removes the FGF signaling antagonist Spry2 have cleft palate. We show that excessive cell proliferation in the Spry2-deficient palate is accompanied by the abnormal progression of shape changes and movements required for medially directed shelf outgrowth and midline contact. Expression of the FGF responsive transcription factors Etv5, Msx1, and Barx1, as well as the morphogen Shh, is restricted to specific regions of the developing palate. We detected elevated and ectopic expression of these transcription factors and disorganized Shh expression in the Spry2-deficient palate. Mice carrying a targeted disruption of Spry2 fail to complement the craniofacial phenotype characterized in Spry2 deletion mice. Furthermore, a Spry2-BAC transgene rescues the palate defect. However, the BAC transgenic mouse lines express reduced levels of Spry2. The resulting hypomorphic phenotype demonstrates that palate development is Spry2 dosage sensitive. Our results demonstrate the importance of proper FGF signaling thresholds in regulation of epithelial-mesenchymal interactions and cellular responses necessary for coordinated morphogenesis of the face and palate.

PMID: 17693063

ICD - Cleft Palate

Q35.1 Q35.3 Q35.5 Q35.7 Q35.9

Q35	Cleft palate
Includes:	fissure of palate palatoschisis
Excludes:	cleft palate with cleft lip ( [#q37 Q37.- ])
Cleft hard palate
Cleft soft palate
Cleft hard palate with cleft soft palate
Cleft uvula
Cleft palate, unspecified

Q36.0 Q36.1 Q36.9

Q36	Cleft lip
Includes:	cheiloschisis congenital fissure of lip harelip labium leporinum
Excludes:	cleft lip with cleft palate ( [#q37 Q37.- ])
Cleft lip, bilateral
Cleft lip, median
Cleft lip, unilateral
Cleft lip NOS

Q37	Cleft palate with cleft lip
Q37.0	Cleft hard palate with bilateral cleft lip
Q37.1	Cleft hard palate with unilateral cleft lip
	Cleft hard palate with cleft lip NOS
Q37.2	Cleft soft palate with bilateral cleft lip
Q37.3	Cleft soft palate with unilateral cleft lip
	Cleft soft palate with cleft lip NOS
Q37.4	Cleft hard and soft palate with bilateral cleft lip
Q37.5	Cleft hard and soft palate with unilateral cleft lip
	Cleft hard and soft palate with cleft lip NOS
Q37.8	Unspecified cleft palate with bilateral cleft lip
Q37.9	Unspecified cleft palate with unilateral cleft lip
	Cleft palate with cleft lip NOS