The palate anatomically separates the nasal cavity from the oral cavity and structurally has a bony (hard) anterior component and a muscular (soft) posterior component ending with the uvula. The oral side of the palate is covered with a squamous stratified (pluristratified) epithelium. The surface of the hard palate of most mammalian species is further thrown into a series of transversal palatal ridges or rugae palatinae. Both the palatal ridge number and arrangement are also species specific.
Neural crest has a major contribution to the palate development and there are a number of molecular, mechanical and morphological steps in involving the fusion of contributing structures including a key epithelial to mesenchymal transition. In palate formation there are two main and separate times and events of development, during embryonic (primary palate) and an early fetal (secondary palate). This separation of events into embryonic and fetal period corresponds closely to the classification of associated palate abnormalities.
The primary palate is formed by two parts:
- maxillary components of the first pharyngeal arch (lateral)
- frontonasal prominence (midline)
The secondary palate can also be divided in two anatomical parts:
- anterior hard palate - ossified (contributions from the maxilla and palatine bones).
- posterior soft palate - muscular.
Some Recent Findings
- Short stature homeobox 2 (SHOX2) regulates osteogenic differentiation and pattern formation during hard palate development in mice "During mammalian palatogenesis, cranial neural crest-derived mesenchymal cells undergo osteogenic differentiation and form the hard palate, which is divided into palatine process of the maxilla and the palatine. However, it remains unknown whether these bony structures originate from the same cell lineage and how the hard palate is patterned at the molecular level. Using mice, here we report that deficiency in short stature homeobox 2 (Shox2), a transcriptional regulator whose expression is restricted to the anterior palatal mesenchyme, leads to a defective palatine process of the maxilla, but does not affect the palatine. Shox2 overexpression in palatal mesenchyme resulted in a hyperplastic palatine process of the maxilla and a hypoplastic palatine. RNA-Seq and assay for transposase-accessible chromatin (ATAC)-Seq analyses revealed that SHOX2 controls the expression of pattern-specification and skeletogenic genes associated with accessible chromatin in the anterior palate. This highlighted a lineage-autonomous function of SHOX2 in patterning and osteogenesis of the hard palate. H3K27ac ChIP-Seq and transient transgenic enhancer assays revealed that SHOX2 binds distal-acting cis-regulatory elements in an anterior palate-specific manner. Our results suggest that the palatine process of the maxilla and palatine arise from different cell lineages and differ in ossification mechanisms. SHOX2 evidently controls osteogenesis of a cell lineage and contributes to the palatine process of the maxilla by interacting with distal cis-regulatory elements to regulate skeletogenic gene expression and to pattern the hard palate. Genome-wide SHOX2 occupancy in the developing palate may provide a marker for identifying active anterior palate-specific gene enhancers."
- TGF-beta (TGF-β) Signaling and the Epithelial-Mesenchymal Transition during Palatal Fusion "Signaling by transforming growth factor TGF-beta plays an important role in development, including in palatogenesis. The dynamic morphological process of palatal fusion occurs to achieve separation of the nasal and oral cavities. Critically and specifically important in palatal fusion are the medial edge epithelial (MEE) cells, which are initially present at the palatal midline seam and over the course of the palate fusion process are lost from the seam, due to cell migration, epithelial mesenchymal transition (EMT), and/or programed cell death. ...mouse TGF-β is highly regulated both temporally and spatially, with TGF-β3 and Smad2 being the preferentially expressed signaling molecules in the critical cells of the fusion processes."
- Development of Hard and Soft Palate During the Fetal Period and Hard Palate Asymmetry "In the present study, it was aimed to perform the morphometric analysis of the hard and soft palate in fetal cadavers and evaluate hard palate asymmetry during the fetal development. The development of the palate was investigated in 40 (21 males, 19 females) fetal materials aged between the 17th and 40th gestational week. In this study, distances between the incisive papilla-staurion (Ip-Sr), staurion-posterior nasal spine (Sr-Pns), incisive papilla-greater palatine foramen (Ip-Gpf) on the right and left sides, Sr-Gpf, and Pns-Gpf were measured. In cases with asymmetry, the ratio of asymmetry was determined in percentage using the asymmetry index. Moreover, angular values between Ip-Sr-Gpf and Ip-Pns-Gpf on the right and left sides were measured, and the right and left side values were compared with each other."
- Ectopic Hedgehog Signaling Causes Cleft Palate and Defective Osteogenesis "Cleft palate is a common birth defect that frequently occurs in human congenital malformations caused by mutations in components of the Sonic Hedgehog (SHH) signaling cascade. Shh is expressed in dynamic, spatiotemporal domains within epithelial rugae and plays a key role in driving epithelial-mesenchymal interactions that are central to development of the secondary palate. However, the gene regulatory networks downstream of Hedgehog (Hh) signaling are incompletely characterized. Here, we show that ectopic Hh signaling in the palatal mesenchyme disrupts oral-nasal patterning of the neural crest cell-derived ectomesenchyme of the palatal shelves, leading to defective palatine bone formation and fully penetrant cleft palate. We show that a series of Fox transcription factors, including the novel direct target Foxl1, function downstream of Hh signaling in the secondary palate. Furthermore, we demonstrate that Wnt/bone morphogenetic protein (BMP) antagonists, in particular Sostdc1, are positively regulated by Hh signaling, concomitant with down-regulation of key regulators of osteogenesis and BMP signaling effectors."
- Three-dimensional imaging of palatal muscles in the human embryo and fetus: Development of levator veli palatini and clinical importance of the lesser palatine nerve "The development of LVP in human embryos and fetuses has not been systematically analyzed using the Carnegie stage (CS) to standardize documentation of development. The anlage of LVP starts to develop at CS 21 beneath the aperture of the auditory tube (AT) to the pharynx. At CS 23, LVP runs along AT over its full length, as evidenced by three-dimensional image reconstruction. In the fetal stage, the lesser palatine nerve (LPN) is in contact with LVP. The positional relationship between LVP and AT three-dimensionally, suggesting that LVP might be derived from the second branchial arch. Based on histological evidence, we hypothesize that motor components from the facial nerve may run along LPN, believed to be purely sensory. The multiple innervation of LVP by LPN and pharyngeal plexus may explain the postpalatoplasty discrepancy between the partial impairment in articulation vs. the functional restoration of deglutition. That is, the contribution of LPN is greater in articulation than in deglutition."
- Molecular Anatomy of Palate Development "The NIH FACEBASE consortium was established in part to create a central resource for craniofacial researchers. One purpose is to provide a molecular anatomy of craniofacial development. To this end we have used a combination of laser capture microdissection and RNA-Seq to define the gene expression programs driving development of the murine palate. We focused on the E14.5 palate, soon after medial fusion of the two palatal shelves. The palate was divided into multiple compartments, including both medial and lateral, as well as oral and nasal, for both the anterior and posterior domains. A total of 25 RNA-Seq datasets were generated. The results provide a comprehensive view of the region specific expression of all transcription factors, growth factors and receptors. Paracrine interactions can be inferred from flanking compartment growth factor/receptor expression patterns. The results are validated primarily through very high concordance with extensive previously published gene expression data for the developing palate."
|These papers originally appeared in the Some Recent Findings table, but as that list grew in length have now been shuffled down to this collapsible table.
See also the Discussion Page for other references listed by year and References on this current page.
- Regulation of the Epithelial Adhesion Molecule CEACAM1 Is Important for Palate Formation "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. ...These results suggest that CEACAM1 has roles in the initiation of palatal fusion via epithelial cell adhesion."
- Role of GSK-3β in the Osteogenic Differentiation of Palatal Mesenchyme "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."
- Ephrin reverse signaling controls palate fusion via a PI3 kinase-dependent mechanism "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."
- A genome-wide association study of cleft lip with and without cleft palate identifies risk variants near MAFB and ABCA4 "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."
- A dosage-dependent role for Spry2 in growth and patterning during palate development "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."
- The Developing Human: Clinically Oriented Embryology (8th Edition) by Keith L. Moore and T.V.N Persaud - Moore & Persaud Chapter Chapter 10 The Pharyngeal Apparatus pp201 - 240.
- Larsen’s Human Embryology by GC. Schoenwolf, SB. Bleyl, PR. Brauer and PH. Francis-West - Chapter 12 Development of the Head, the Neck, the Eyes, and the Ears pp349 - 418.
- Links: Movies | ultrasound
- week 4 - pharyngeal arch formation, first pharngeal arch contributes mandible and maxilla.
- week 6 - 7 - primary palate formation maxillary processes and frontonasal prominence.
- week 9 - secondary palate shelves fuse, separating oral and nasal cavities.
- (week 4) - pharyngeal arch formation in rostrocaudal sequence (1, 2, 3, 4 and 6)
- First pharyngeal arch - upper maxillary (pair) and lower mandibular prominences
- Late embryonic period - maxillary prominences fuse with frontonasal prominence forming upper jaw (maxilla and upper lip)
- palatal shelves elevation
- palatal shelves midline fusion
Pharyngeal Arch Development
Major features to identify for each: arch, pouch, groove and membrane. Contribute to the formation of head and neck and in the human appear at the 4th week. The first arch contributes the majority of upper and lower jaw structures.
- Pharynx - begins at the buccopharyngeal membrane (oral membrane), apposition of ectoderm with endoderm (no mesoderm between).
- branchial arch (Gk. branchia= gill)
- arch consists of all 3 trilaminar embryo layers
- ectoderm - outside
- mesoderm - core of mesenchyme
- endoderm - inside
- Mesenchyme invaded by neural crest generating connective tissue components
- cartilage, bone, ligaments
- arises from midbrain and hindbrain region
Begins week 4 centered around stomodeum, external depression at oral membrane
5 initial primordia from neural crest mesenchyme
- single frontonasal prominence (FNP) - forms forehead, nose dorsum and apex
- nasal placodes develop later bilateral, pushed medially
- paired maxillary prominences - form upper cheek and upper lip
- paired mandibular prominences - lower cheek, chin and lower lip
The frontonasal process (FNP) forms the majority of the superior part of the early face primordia. It later fuses with the maxillary component of the first pharyngeal arch to form the upper jaw. Failure of this fusion event during the embryonic period leads to cleft lip. Under the surface ectoderm the process mesenchyme consists of two cell populations; neural crest cells, forming the connective tissues; and the mesoderm forming the endothelium of the vascular network.
A chicken developmental model study has identified a specific surface region, the Frontonasal Ectodermal Zone (FEZ), initially induced by bone morphogenetic proteins that appears to regulate the future growth and patterning of the frontonasal process. The specific frontonasal ectodermal zone was located in the frontonasal process ectoderm flanking a boundary between Sonic hedgehog (SHH) and Fibroblast growth factor 8 (FGF8) expression domains.
Human primary palate
- develops between embryonic stages 15 and 18.
- fusion in the human embryo between stage 17 and 18, from an epithelial seam to the mesenchymal bridge.
- EM Links: Image - stage 16 | Image - stage 17 | Image - stage 18 | Image - stage 19
|Secondary palate, fusion in the human embryo in week 9. This requires the early palatal shelves growth, elevation, and fusion. There are many fusion events occurring during this period between each palatal shelf, to the primary palate, and also to the nasal septum.
palatal shelf elevation | secondary palate
Detail - hard and soft palate junction
Detail - hard palate seam
Fetal Palate Growth (second trimester)
Fetal week 9 (GA week 11) hard palate fusion
Ventral aspect of hard palate of human embryo of 80 mm
The soft palate mechanism of closure has not yet been determined, with several existing theories. A recent study of embryos from the late embryonic-early fetal period (54 to 74 days post-conception) has identified the timing of soft palate closure.
- 57 days - Late embryonic (Carnegie stage 23), epithelial seam present throughout the soft palate
- 64 days - Early fetal (Week 9), epithelium only persists in the most posterior regions of the soft palate
Postnatal Head Changes
Head Growth continues postnatally with fontanelle initially allowing head distortion on birth and early growth. These bony plates remain unfused to allow growth, puberty growth of face.
The palate also grows postnatally through childhood and becomes more elevated (arched) forming the "palatine vault", with different (but insignificant) growth between the genders.
- Links: Postnatal Development
- E11 - protrude from bilateral maxillary processes
- E12.5 - secondary palatal development begins
- E12.5-E14 - grow vertically along the developing tongue
- E14.5 - they elevate, meet, and fuse at the midline, to form an intact palate shelf, reflex opening and closing movements of the mouth
- E15.5 - palatal fusion is complete, mesenchymal condensation followed by osteogenic differentiation occurs.
Mouse (E13.5) Palatal Shelf Wnt5a, Osr2 and Pax9 Expression.
Image - Mouse E13.5 Bmp7 palate
|Mouse ruga pattern (E16)
||Mouse - Spry1 cleft palate
- Links: Mouse Development | Bone Morphogenetic Protein | Wnt | Pax
Newborn dog with cleft palate
Image - Mouse E13.5 Bmp7 palate PMID 23516636
Image - palate Bmp7 palate PMID 23516636
Image - palate detail Bmp7 palate PMID 23516636
- Links: Bone Morphogenetic Protein
Note there are specific pages for both Cleft Lip and Palate and Cleft Palate.
Complete Unilateral cleft lip and palate
Complete Unilateral cleft lip and palate
Complete bilateral cleft lip and palate
Complete bilateral cleft lip and palate
Cheiloplasty - surgical repair of the lip
Palatoplasty - surgical repair of the palate
Cleft Palate - Australia (1981-1992)
The way in which the upper jaw forms from fusion of the smaller upper prominence of the first pharyngeal arch leads to a common congenital defect in this region called "clefting", which may involve either the upper lip, the palate or both structures.
|Australian Palate Abnormalities (2002-2003)
|Cleft lip with or without cleft palate (9.2 per 10,000 births) ICD-10 Q36.0, Q36.1, Q36.9, Q37.0–Q37.5, Q37.8, Q37.9
|A congenital anomaly characterised by a partial or complete clefting of the upper lip, with or without clefting of the alveolar ridge or the hard palate. Excludes a midline cleft of the upper or lower lip and an oblique facial fissure (going towards the eye).
- 17% of the affected pregnancies were terminated in early pregnancy or resulted in fetal deaths. Most of the fetal deaths or terminations of pregnancy (95%) had multiple abnormalities.
- more commonly seen in males than in females.
- babies born before 25 weeks of gestation, 150 per 10,000 births had this anomaly. Most babies (80.0%) were born at term with a birthweight of 2,500 grams or more.
- Maternal age group was not associated with the anomaly.
- Rates significantly higher among Indigenous women than non Indigenous women.
|Cleft palate without cleft lip (8.1 per 10,000 births) ICD-10 Q35.0–Q35.9
|A congenital anomaly characterised by a closure defect of the hard and/or soft palate behind the foramen incisivum without a cleft lip. This anomaly includes sub-mucous cleft palate, but excludes cleft palate with a cleft lip, a functional short palate and high narrow palate.
- overall rate has increased to 9.1 when the rate was estimated using data from the four states that include TOP data. The reported number of fetal deaths or early terminations of pregnancy with this anomaly was small and these deaths or terminations could be due to other associated anomalies.
- proportion of females with this anomaly was higher (56.9%) than males.
- 52.7 per 10,000 babies born before 25 weeks of gestation.
- 83.0% were born at term and most of the babies (82.7%) had a birthweight of 2,500 grams or more.
- Women aged 40 years or older and women born in South Central America or the Caribbean region had the highest rates of affected births.
- Multiple births had a significantly higher rate of affected babies than singleton births.
- Rates did not differ significantly by Indigenous status or areas of residence.
- Links: Palate Development | Head Development | Gastrointestinal Tract - Abnormalities | ICD-10 GIT | Australian Statistics
- Reference: Abeywardana S & Sullivan EA 2008. Congenital Anomalies in Australia 2002-2003. Birth anomalies series no. 3 Cat. no. PER 41. Sydney: AIHW National Perinatal Statistics Unit.
|Global Orofacial Cleft Rate (1950 - 2015)
|This data is from a study of the published data (1950 - 2015)
||Orofacial cleft rate /1,000 live births (95% confidence interval)
- American Indians 2.62 per 1,000 live births (highest prevalence rates)
- Japanese 1.73
- Chinese 1.56
- Whites 1.55
- Blacks 0.58 (lowest prevalence rates)
International Classification of Diseases - Cleft Palate
Cleft lip and cleft palate (Q35-Q37)
Use additional code (Q30.2), if desired, to identify associated malformations of the nose. Excludes Robin's syndrome ( Q87.0 )
||Cleft palate with cleft lip
||Cleft hard palate with bilateral cleft lip
||Cleft hard palate with unilateral cleft lip
||Cleft hard palate with cleft lip NOS
||Cleft soft palate with bilateral cleft lip
||Cleft soft palate with unilateral cleft lip
||Cleft soft palate with cleft lip NOS
||Cleft hard and soft palate with bilateral cleft lip
||Cleft hard and soft palate with unilateral cleft lip
||Cleft hard and soft palate with cleft lip NOS
||Unspecified cleft palate with bilateral cleft lip
||Unspecified cleft palate with unilateral cleft lip
||Cleft palate with cleft lip NOS
Embryonic Human Cleft Palate
|Stage16 (ventral view)
- International Classification of Diseases code 749.1 for isolated cleft lip and 749.2 for cleft lip with cleft palate.
- Australian national rate (1982-1992) 8.1 - 9.9 /10,000 births.
- Of 2,465 infants 6.2% were stillborn and 7.8% liveborn died during neonatal period.
- rate similar in singleton and twin births.
|Cleft Lip Genes
|Midline Cleft Lip Genes
- Opitz G/BBB (MID1)
- Oro-facial-digital type I (OFD1)
Cleft Lip (+/− cleft palate) Genes
|Autosomal dominant developmental malformations, deafness, and dystonia
|Familial gastric cancer and CLP
|Van der Woude/popliteal pterygium
|X-linked mental retardation and CL/P
|CLP – ectodermal dysplasia
|Tetra-amelia with CLP
An 8 month old infant with an extensive cleft palate associated with Bamforth- Lazarus syndrome.
- International Classification of Diseases code 749.0
- Australian national rate (1982-1992) 4.8 - 6 /10,000 births.
- Of 1,530 infants 5.5% were stillborn and 11.5% liveborn died during neonatal period.
- slightly more common in twin births than singleton.
(Data: Congenital Malformations Australia 1981-1992 P. Lancaster and E. Pedisich ISSN 1321-8352)
|Cleft Palate Only Genes
|Lethal and Escobar multiple pterygium
|Stickler type 1
|Stickler type 2
|Stickler type 3
|Otopalatodigital types 1 and 2
|Larsen syndrome; atelosteogenesis
|Van der Woude/popliteal pterygium
|Cornelia de Lange
|X-linked mental retardation
|Isolated cleft palate
|X-linked cleft palate and ankyloglossia
Links: OMIM Orofacial Cleft with or without cleft palate
Search Pubmed Now: cleft lip | cleft palate
Cleft Risk Variants
Two genes were identified from a recent genome-wide study.
- MAFB is expressed in the mouse palatal shelf.
- ABCA4 is a member of a superfamily of transmembrane proteins, and mutations in ABCA4 play a major role in the etiology of Stargardt disease and related retinopathies. Gene produces an ATP-binding cassette (ABC) superfamily trans-membrane protein
- Links: OMIM - MAFB | OMIM - ABCA4
Ten most frequently reported Birth Anomalies
- Hypospadias (More? Male movie | Genital Abnormalities - Hypospadia)
- Obstructive Defects of the Renal Pelvis (More? Renal System - Abnormalities)
- Ventricular Septal Defect (More? Cardiovascular Abnormalities - Ventricular Septal Defect)
- Congenital Dislocated Hip (More? Musculoskelal Abnormalities - Congenital Dislocation of the Hip (CDH))
- Trisomy 21 or Down syndrome - (More? Trisomy 21)
- Hydrocephalus (More? Hydrocephalus)
- Cleft Palate (More? Palate_Development)
- Trisomy 18 or Edward Syndrome - multiple abnormalities of the heart, diaphragm, lungs, kidneys, ureters and palate 86% discontinued (More? (More? Trisomy 18)
- Renal Agenesis/Dysgenesis - reduction in neonatal death and stillbirth since 1993 may be due to the more severe cases being identified in utero and being represented amongst the increased proportion of terminations (approximately 31%). (More? Renal System - Abnormalities)
- Cleft Lip and Palate - occur with another defect in 33.7% of cases.(More? Palate Development | Head Development)
(From the Victorian Perinatal Data Collection Unit in the Australian state of Victoria between 2003-2004)
A recent study of periconceptional folate supplementation using the Cochrane Pregnancy and Childbirth Group's Trials Register (July 2010) identified no statistically significant evidence of any effects on prevention of cleft palate and cleft lip at birth.
- ↑ Xu J, Wang L, Li H, Yang T, Zhang Y, Hu T, Huang Z & Chen Y. (2019). Short stature homeobox 2 (SHOX2) regulates osteogenic differentiation and pattern formation during hard palate development in mice. J. Biol. Chem. , , . PMID: 31649032 DOI.
- ↑ Nakajima A, F Shuler C, Gulka AOD & Hanai JI. (2018). TGF-β Signaling and the Epithelial-Mesenchymal Transition during Palatal Fusion. Int J Mol Sci , 19, . PMID: 30463190 DOI.
- ↑ Dursun A, Öztürk K & Albay S. (2018). Development of Hard and Soft Palate During the Fetal Period and Hard Palate Asymmetry. J Craniofac Surg , 29, 2358-2362. PMID: 30320695 DOI.
- ↑ Hammond NL, Brookes KJ & Dixon MJ. (2018). Ectopic Hedgehog Signaling Causes Cleft Palate and Defective Osteogenesis. J. Dent. Res. , 97, 1485-1493. PMID: 29975848 DOI.
- ↑ Kishimoto H, Yamada S, Kanahashi T, Yoneyama A, Imai H, Matsuda T, Takeda T, Kawai K & Suzuki S. (2016). Three-dimensional imaging of palatal muscles in the human embryo and fetus: Development of levator veli palatini and clinical importance of the lesser palatine nerve. Dev. Dyn. , 245, 123-31. PMID: 26509917 DOI.
- ↑ Potter AS & Potter SS. (2015). Molecular Anatomy of Palate Development. PLoS ONE , 10, e0132662. PMID: 26168040 DOI.
- ↑ Mima J, Koshino A, Oka K, Uchida H, Hieda Y, Nohara K, Kogo M, Chai Y & Sakai T. (2013). Regulation of the epithelial adhesion molecule CEACAM1 is important for palate formation. PLoS ONE , 8, e61653. PMID: 23613893 DOI.
- ↑ Nelson ER, Levi B, Sorkin M, James AW, Liu KJ, Quarto N & Longaker MT. (2011). Role of GSK-3β in the osteogenic differentiation of palatal mesenchyme. PLoS ONE , 6, e25847. PMID: 22022457 DOI.
- ↑ San Miguel S, Serrano MJ, Sachar A, Henkemeyer M, Svoboda KK & Benson MD. (2011). Ephrin reverse signaling controls palate fusion via a PI3 kinase-dependent mechanism. Dev. Dyn. , 240, 357-64. PMID: 21246652 DOI.
- ↑ 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, Scott JM, Arcos-Burgos M & Scott AF. (2010). A genome-wide association study of cleft lip with and without cleft palate identifies risk variants near MAFB and ABCA4. Nat. Genet. , 42, 525-9. PMID: 20436469 DOI.
- ↑ Welsh IC, Hagge-Greenberg A & O'Brien TP. (2007). A dosage-dependent role for Spry2 in growth and patterning during palate development. Mech. Dev. , 124, 746-61. PMID: 17693063 DOI.
- ↑ Foppiano S, Hu D & Marcucio RS. (2007). Signaling by bone morphogenetic proteins directs formation of an ectodermal signaling center that regulates craniofacial development. Dev. Biol. , 312, 103-14. PMID: 18028903 DOI.
- ↑ Diewert VM & Lozanoff S. (1993). A morphometric analysis of human embryonic craniofacial growth in the median plane during primary palate formation. J. Craniofac. Genet. Dev. Biol. , 13, 147-61. PMID: 8227288
- ↑ BURDI AR. (1965). SAGITTAL GROWTH OF THE NASOMAXILLARY COMPLEX DURING THE SECOND TRIMESTER OF HUMAN PRENATAL DEVELOPMENT. J. Dent. Res. , 44, 112-25. PMID: 14245486 DOI.
- ↑ Danescu A, Mattson M, Dool C, Diewert VM & Richman JM. (2015). Analysis of human soft palate morphogenesis supports regional regulation of palatal fusion. J. Anat. , 227, 474-86. PMID: 26299693 DOI.
- ↑ Yang ST, Kim HK, Lim YS, Chang MS, Lee SP & Park YS. (2013). A three dimensional observation of palatal vault growth in children using mixed effect analysis: a 9 year longitudinal study. Eur J Orthod , 35, 832-40. PMID: 23314328 DOI.
- ↑ Almaidhan A, Cesario J, Landin Malt A, Zhao Y, Sharma N, Choi V & Jeong J. (2014). Neural crest-specific deletion of Ldb1 leads to cleft secondary palate with impaired palatal shelf elevation. BMC Dev. Biol. , 14, 3. PMID: 24433583 DOI.
- ↑ P. Lancaster and E. Pedisich, Congenital Malformations Australia 1981-1992, ISSN 1321-835.
- ↑ <pubmed>26742364</pubmed>
- ↑ 20.0 20.1 Dixon MJ, Marazita ML, Beaty TH & Murray JC. (2011). Cleft lip and palate: understanding genetic and environmental influences. Nat. Rev. Genet. , 12, 167-78. PMID: 21331089 DOI.
- ↑ Rastogi MV & LaFranchi SH. (2010). Congenital hypothyroidism. Orphanet J Rare Dis , 5, 17. PMID: 20537182 DOI.
- ↑ Cite error: Invalid
<ref> tag; no text was provided for refs named
- ↑ De-Regil LM, Fernández-Gaxiola AC, Dowswell T & Peña-Rosas JP. (2010). Effects and safety of periconceptional folate supplementation for preventing birth defects. Cochrane Database Syst Rev , , CD007950. PMID: 20927767 DOI.
Indian J Plast Surg. 2009 October; 42(Suppl):Cleft Lip and Palate Issue
Nakajima A, F Shuler C, Gulka AOD & Hanai JI. (2018). TGF-β Signaling and the Epithelial-Mesenchymal Transition during Palatal Fusion. Int J Mol Sci , 19, . PMID: 30463190 DOI.
Tarr JT, Lambi AG, Bradley JP, Barbe MF & Popoff SN. (2018). Development of Normal and Cleft Palate: A Central Role for Connective Tissue Growth Factor (CTGF)/CCN2. J Dev Biol , 6, . PMID: 30029495 DOI.
Weng M, Chen Z, Xiao Q, Li R & Chen Z. (2018). A review of FGF signaling in palate development. Biomed. Pharmacother. , 103, 240-247. PMID: 29655165 DOI.
Lan Y, Xu J & Jiang R. (2015). Cellular and Molecular Mechanisms of Palatogenesis. Curr. Top. Dev. Biol. , 115, 59-84. PMID: 26589921 DOI.
Suzuki A, Sangani DR, Ansari A & Iwata J. (2016). Molecular mechanisms of midfacial developmental defects. Dev. Dyn. , 245, 276-93. PMID: 26562615 DOI.
Abramyan J & Richman JM. (2015). Recent insights into the morphological diversity in the amniote primary and secondary palates. Dev. Dyn. , 244, 1457-68. PMID: 26293818 DOI.
Bush JO & Jiang R. (2012). Palatogenesis: morphogenetic and molecular mechanisms of secondary palate development. Development , 139, 231-43. PMID: 22186724 DOI.
Meng L, Bian Z, Torensma R & Von den Hoff JW. (2009). Biological mechanisms in palatogenesis and cleft palate. J. Dent. Res. , 88, 22-33. PMID: 19131313 DOI.
Dudas M, Li WY, Kim J, Yang A & Kaartinen V. (2007). Palatal fusion - where do the midline cells go? A review on cleft palate, a major human birth defect. Acta Histochem. , 109, 1-14. PMID: 16962647 DOI.
Ferguson MW. (1988). Palate development. Development , 103 Suppl, 41-60. PMID: 3074914
Hay ED. (1995). An overview of epithelio-mesenchymal transformation. Acta Anat (Basel) , 154, 8-20. PMID: 8714286
Hammond NL, Brookes KJ & Dixon MJ. (2018). Ectopic Hedgehog Signaling Causes Cleft Palate and Defective Osteogenesis. J. Dent. Res. , 97, 1485-1493. PMID: 29975848 DOI.
Sun L, Wang J, Liu H, Fan Z, Wang S & Du J. (2017). A Comprehensive Study of Palate Development in Miniature Pig. Anat Rec (Hoboken) , 300, 1409-1419. PMID: 28296336 DOI.
Steding G & Jian Y. (2010). The origin and early development of the nasal septum in human embryos. Ann. Anat. , 192, 82-5. PMID: 20149609 DOI.
Xiong W, He F, Morikawa Y, Yu X, Zhang Z, Lan Y, Jiang R, Cserjesi P & Chen Y. (2009). Hand2 is required in the epithelium for palatogenesis in mice. Dev. Biol. , 330, 131-41. PMID: 19341725 DOI.
Search Pubmed: palate development | cleft palate development |
Nasal cavities and palate
Palate, tongue and Meckel's cartilage
Unilateral cleft lip and palate
Fig. 6. Showing the structures formed in the Lateral Nasal Processes.
Fig. 7. Coronal section of the skull of a 7th month human foetus to show the cartilages of the Lateral and Mesial Nasal Processes and the bones formed round them.
Fig. 8. Showing the ingrowth of the palatal plates of the two maxillary processes early in the 2nd month. (After Kollmann.) .
Fig. 9. Showing the Hard Palate at birth. The premaxillary part is formed from the Mesial Nasal Processes ; the remainder by the Palatal Plates of the Maxillary Processes.
Fig. 10, a, b, c. Showing what become of the skeletons of the Mandibular Arch (Meckel's Cartilage) and Maxillary Process (Palato-quadrate Cartilage).
Fig. 11. Showing the manner in which the development of the Maxillary Antrum affects the size of the palate and position of the molar teeth.
|Palate Development (expand to see terms)
- cleft - An anatomical gap or space occuring in abnormal development in or between structures. Most commonly associated with cleft lip and cleft palate. Term is also used to describe the external groove that forms between each pharyngeal arch during their formation.
- cleft lip - An abnormality of face development leading to an opening in the upper lip. Clefting of the lip and or palate occurs with 300+ different abnormalities. Depending on many factors, this cleft may extend further into the oral cavity leading to a cleft palate. In most cases clefting of the lip and palate can be repaired by surgery.
- cleft palate - An abnormality of face development leading to an opening in the palate, the roof of the oral cavity between the mouth and the nose. Clefting of the lip and or palate occurs with 300+ different abnormalities. In most cases clefting of the lip and palate can be repaired by surgery. Palate formation in the embryo occurs at two distinct times and developmental processes called primary and secondary palate formation. This leads to different forms (classifications) and degrees of clefting.
- hard palate - anterior part of the palate that becomes ossified. The posterior palate part is the soft palate.
- epithelial mesenchymal transition - (EMT, epitheliomesenchymal transformation) conversion of an epithelium into a mesenchymal (connective tissue) cellular organization. Process required during lip and palate developmental fusion.
- epitheliomesenchymal transformation - (epithelial mesenchymal transition) conversion of an epithelium into a mesenchymal (connective tissue) cellular organization.
- incisive papilla - anterior midline palate near the incisors lying at the end of the palatine raphe.
- levator veli palatini - Muscle forming part of the soft palate, elevates the soft palate for swallowing.
- mastication - (chewing) Process of crushing and grinding food within the mouth.
- maxilla - (pl. maxillae) upper jaw bone forming from the maxillary process of the first pharyngeal arch.
- medial edge epithelial - (MEE) opposing palatal shelves adhere to each other to form this epithelial seam.
- musculus uvulae Small muscle forming part of the soft palate lying within the uvula, shortens and broadens the uvula.
- palatine raphe (median raphe) palate midline ridge (seam) of the mucosa, from the incisive papilla to the uvula.
- palatal rugae - (palatine rugae, rugae) Transverse series of ridges forming on the secondary hard palate that are sequentially added during development as the palate grows. Involved in the process of mastication.
- palatal vault - (palatine vault) Term describing the curved "arch" shape of the palate that mainly develops postnatally.
- palate - The roof of the mouth (oral cavity) a structure which separates the oral from the nasal cavity. Develops as two lateral palatal shelves which grow and fuse in the midline. Initally a primary palate forms with fusion of the maxillary processes with the nasal processes in early face formation. Later the secondary palate forms the anterior hard palate which will ossify and separate the oral and nasal cavities. The posterior part of the palate is called the soft palate (velum, muscular palate) and contains no bone. Abnormalities of palatal shelf fusion can lead to cleft palate.
- palatine bones - Two bones that with the maxillae form the hard palate.
- palatogenesis - The process of palate formation, divided into primary and secondary palate development.
- palatoglossus - (glossopalatinus, palatoglossal muscle) Small muscle forming part of the soft palate required for swallowing.
- palatopharyngeus - (palatopharyngeal or pharyngopalatinus) Small muscle forming part of the soft palate required for breathing.
- pharyngeal arch - (branchial arch, Greek, branchial = gill) These are a series of externally visible anterior tissue bands lying under the early brain that give rise to the structures of the head and neck. In humans, five arches form (1,2,3,4 and 6) but only four are externally visible on the embryo. Each arch has initially identical structures: an internal endodermal pouch, a mesenchymal (mesoderm and neural crest) core, a membrane (endoderm and ectoderm) and external cleft (ectoderm). Each arch mesenchymal core also contains similar components: blood vessel, nerve, muscular, cartilage. Each arch though initially formed from similar components will differentiate to form different head and neck structures.
- philtrum - (infranasal depression, Greek, philtron = "to love" or "to kiss") Anatomically the surface midline vertical groove in the upper lip. Embryonically formed by the fusion of the frontonasal prominence (FNP) with the two maxillary processes of the first pharyngeal arch. Cleft palate (primary palate) occurs if these three regions fail to fuse during development. Fetal alcohol syndrome is also indicated by flatness and extension of this upper lip region.
- soft palate - (velum, muscular palate) posterior part of the palate that becomes muscular. Forms 5 muscles: tensor veli palatini, palatoglossus, palatopharyngeus, levator veli palatini, musculus uvulae. The anterior palate part is the hard palate.
- T-box 22 - (TBX22) a transcription factor that cause X-linked cleft palate and ankyloglossia in humans. Tbx22 is induced by fibroblast growth factor 8 (FGF8) in the early face while bone morphogenic protein 4 (BMP4) represses and therefore restricts its expression. (More? OMIM - TBX22)
- tensor veli palatini - (tensor palati, tensor muscle of the velum palatinum) Small muscle forming part of the soft palate required for swallowing.
- Transforming Growth Factor-beta - (TGFβ) factors induces both epithelial mesenchymal transition and/or apoptosis during palatal medial edge seam disintegration.
- uvula - (Latin = a little grape) a pendulous posterior end of soft palate used to produce guttural consonants. First named in 1695.
- Van der Woude syndrome - common syndromic cause of clefting (2% of cleft lip and palates). Van der Woude syndrome 1 1q32.2 Van der Woude syndrome 2 1p36.11
- velopharyngeal insufficiency - (VPI) associated with cleft palate repair, describes the velum and lateral and posterior pharyngeal walls failing to separate the oral cavity from the nasal cavity during speech.
External Links Notice - The dynamic nature of the internet may mean that some of these listed links may no longer function. If the link no longer works search the web with the link text or name. Links to any external commercial sites are provided for information purposes only and should never be considered an endorsement. UNSW Embryology is provided as an educational resource with no clinical information or commercial affiliation.
- Glossary: A | B | C | D | E | F | G | H | I | J | K | L | M | N | O | P | Q | R | S | T | U | V | W | X | Y | Z | Numbers | Symbols | Term Link
Cite this page: Hill, M.A. (2021, May 11) Embryology Palate Development. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Palate_Development
- What Links Here?
- © Dr Mark Hill 2021, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G