|Embryology - 25 Oct 2016 Expand to Translate|
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- 1 Introduction
- 2 Some Recent Findings
- 3 Textbooks
- 4 Movies
- 5 Development Overview
- 6 Pharyngeal Arch Development
- 7 Face Development
- 8 Embryonic Palate
- 9 Fetal Palate
- 10 Soft Palate
- 11 Head Growth
- 12 Animal Palate
- 13 Molecular
- 14 Abnormalities
- 15 Cleft Risk Variants
- 16 References
- 17 Additional Images
- 18 Terms
- 19 External Links
- 20 Glossary Links
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.
- Palate Links: Palate Development | Cleft Lip and Palate | Cleft Palate | Head Development | Category:Palate
Some Recent Findings
|More recent papers|
This table shows an automated computer PubMed search using the listed sub-heading term.
References listed on the rest of the content page and the associated discussion page (listed under the publication year sub-headings) do include some editorial selection based upon both relevance and availability.
Gregory S Antonarakis, Bryan D Tompson, David M Fisher Preoperative Cleft Lip Measurements and Maxillary Growth in Patients With Unilateral Cleft Lip and Palate. Cleft Palate Craniofac. J.: 2016, 53(6);e198-e207 PubMed 27776219
Announcements. Cleft Palate Craniofac. J.: 2016, 53(6);754-756 PubMed 27776218
Goran Cuturilo, Danijela Drakulic, Ida Jovanovic, Aleksandar Krstic, Milan Djukic, Dejan Skoric, Marija Mijovic, Igor Stefanovic, Milena Milivojevic, Milena Stevanovic Improving the Diagnosis of Children with 22q11.2 Deletion Syndrome: A Single-center Experience from Serbia. Indian Pediatr: 2016, 53(9);786-789 PubMed 27771646
Elizabeth G Zellner, Julie M Mhlaba, Russell R Reid, Derek Steinbacher Does Mandibular Distraction Vector Influence Airway Volumes and Outcome? J. Oral Maxillofac. Surg.: 2016; PubMed 27718360
Loïc Broix, Hélène Jagline, Ekaterina L Ivanova, Stéphane Schmucker, Nathalie Drouot, Jill Clayton-Smith, Alistair T Pagnamenta, Kay A Metcalfe, Bertrand Isidor, Ulrike Walther Louvier, Annapurna Poduri, Jenny C Taylor, Peggy Tilly, Karine Poirier, Yoann Saillour, Nicolas Lebrun, Tristan Stemmelen, Gabrielle Rudolf, Giuseppe Muraca, Benjamin Saintpierre, Adrienne Elmorjani, Deciphering Developmental Disorders study, Martin Moïse, Nathalie Bednarek Weirauch, Renzo Guerrini, Anne Boland, Robert Olaso, Cecile Masson, Ratna Tripathy, David Keays, Cherif Beldjord, Laurent Nguyen, Juliette Godin, Usha Kini, Patrick Nischké, Jean-François Deleuze, Nadia Bahi-Buisson, Izabela Sumara, Maria-Victoria Hinckelmann, Jamel Chelly Mutations in the HECT domain of NEDD4L lead to AKT-mTOR pathway deregulation and cause periventricular nodular heterotopia. Nat. Genet.: 2016; PubMed 27694961
Bartosz J Płachno, Małgorzata Stpiczyńska, Piotr Świątek, Kevin L Davies Floral micromorphology of the Australian carnivorous bladderwort Utricularia dunlopii, a putative pseudocopulatory species. Protoplasma: 2015; PubMed 26497694
M A Martín-Piedra, M Alaminos, R Fernández-Valadés-Gámez, A España-López, E Liceras-Liceras, I Sánchez-Montesinos, A Martínez-Plaza, M C Sánchez-Quevedo, R Fernández-Valadés, I Garzón Development of a multilayered palate substitute in rabbits: a histochemical ex vivo and in vivo analysis. Histochem. Cell Biol.: 2016; PubMed 27600719
Boris Groisman, Juan Gili, Lucas Giménez, Fernando Poletta, María Paz Bidondo, Pablo Barbero, Rosa Liascovich, Jorge López-Camelo Geographic clusters of congenital anomalies in Argentina. J Community Genet: 2016; PubMed 27541682
Mahmood Khaksary Mahabady, Mohammad Reza Gholami, Hossein Najafzadeh Varzi, Abolfazl Zendedel, Mona Doostizadeh Protective effect of quercetin on skeletal and neural tube teratogenicity induced by cyclophosphamide in rat fetuses. Vet Res Forum: 2016, 7(2);133-8 PubMed 27482358
Adauê Oliveira, Cássia Amaral Rapid Maxillary Expansion without Posterior Anchorage. Int J Orthod Milwaukee: 2016, 27(1);73-6 PubMed 27319047
- 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.
- 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)
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
- EM Links: Image - stage 16 | Image - stage 17 | Image - stage 18 | Image - stage 19 | Palate Development
|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.
Fetal Palate Growth (second trimester)
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
- continues postnatally - fontanelle allow head distortion on birth and early growth
- bone plates remain unfused to allow growth, puberty growth of face
- 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.
|Mouse ruga pattern (E16)||Mouse - Spry1 cleft palate|
Newborn dog with cleft palate
MMP25 PMID 20809987
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
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).
|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.
|Global Orofacial Cleft Rate (1950 - 2015)|
| This data is from a study of the published data (1950 - 2015)
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 )
|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|
Embryonic Human Cleft Palate
|Stage16 (ventral view)|
|Cleft Lip Genes|
| Midline Cleft Lip Genes
Cleft Lip (+/− cleft palate) Genes
(Data: Congenital Malformations Australia 1981-1992 P. Lancaster and E. Pedisich ISSN 1321-8352)
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
Ten most frequently reported Birth Anomalies
- Hypospadias (More? Development Animation - Genital Male External | 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)
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.
- Junko Mima, Aya Koshino, Kyoko Oka, Hitoshi Uchida, Yohki Hieda, Kanji Nohara, Mikihiko Kogo, Yang Chai, Takayoshi Sakai Regulation of the epithelial adhesion molecule CEACAM1 is important for palate formation. PLoS ONE: 2013, 8(4);e61653 PubMed 23613893 | PLoS One.
- Emily R Nelson, Benjamin Levi, Michael Sorkin, Aaron W James, Karen J Liu, Natalina Quarto, Michael T Longaker Role of GSK-3β in the osteogenic differentiation of palatal mesenchyme. PLoS ONE: 2011, 6(10);e25847 PubMed 22022457 | PLoS One.
- Symone San Miguel, Maria J Serrano, Ashneet Sachar, Mark Henkemeyer, Kathy K H Svoboda, M Douglas Benson Ephrin reverse signaling controls palate fusion via a PI3 kinase-dependent mechanism. Dev. Dyn.: 2011, 240(2);357-64 PubMed 21246652
- Terri H Beaty, Jeffrey C Murray, Mary L Marazita, Ronald G Munger, Ingo Ruczinski, Jacqueline B Hetmanski, Kung Yee Liang, Tao Wu, Tanda Murray, M Daniele Fallin, Richard A Redett, Gerald Raymond, Holger Schwender, Sheng-Chih Jin, Margaret E Cooper, Martine Dunnwald, Maria A Mansilla, Elizabeth Leslie, Stephen Bullard, Andrew C Lidral, Lina M Moreno, Renato Menezes, Alexandre R Vieira, Aline Petrin, Allen J Wilcox, Rolv T Lie, Ethylin W Jabs, Yah Huei Wu-Chou, Philip K Chen, Hong Wang, Xiaoqian Ye, Shangzhi Huang, Vincent Yeow, Samuel S Chong, Sun Ha Jee, Bing Shi, Kaare Christensen, Mads Melbye, Kimberly F Doheny, Elizabeth W Pugh, Hua Ling, Eduardo E Castilla, Andrew E Czeizel, Lian Ma, L Leigh Field, Lawrence Brody, Faith Pangilinan, James L Mills, Anne M Molloy, Peadar N Kirke, John M Scott, James M Scott, Mauricio Arcos-Burgos, Alan F Scott A genome-wide association study of cleft lip with and without cleft palate identifies risk variants near MAFB and ABCA4. Nat. Genet.: 2010, 42(6);525-9 PubMed 20436469
- Ian C Welsh, Aaron Hagge-Greenberg, Timothy P O'Brien A dosage-dependent role for Spry2 in growth and patterning during palate development. Mech. Dev.: 2007, 124(9-10);746-61 PubMed 17693063
- Silvia Foppiano, Diane Hu, Ralph S Marcucio Signaling by bone morphogenetic proteins directs formation of an ectodermal signaling center that regulates craniofacial development. Dev. Biol.: 2007, 312(1);103-14 PubMed 18028903
- V M Diewert, S Lozanoff A morphometric analysis of human embryonic craniofacial growth in the median plane during primary palate formation. J. Craniofac. Genet. Dev. Biol.: 1993, 13(3);147-61 PubMed 8227288
- A R BURDI SAGITTAL GROWTH OF THE NASOMAXILLARY COMPLEX DURING THE SECOND TRIMESTER OF HUMAN PRENATAL DEVELOPMENT. J. Dent. Res.: 1965, 44;112-25 PubMed 14245486
- Adrian Danescu, Melanie Mattson, Carly Dool, Virginia M Diewert, Joy M Richman Analysis of human soft palate morphogenesis supports regional regulation of palatal fusion. J. Anat.: 2015; PubMed 26299693
- Asma Almaidhan, Jeffry Cesario, Andre Landin Malt, Yangu Zhao, Neeti Sharma, Veronica Choi, Juhee Jeong Neural crest-specific deletion of Ldb1 leads to cleft secondary palate with impaired palatal shelf elevation. BMC Dev. Biol.: 2014, 14;3 PubMed 24433583 | BMC Dev Biol.
- P. Lancaster and E. Pedisich, Congenital Malformations Australia 1981-1992, ISSN 1321-835.
- Vipawee Panamonta, Suteera Pradubwong, Manat Panamonta, Bowornsilp Chowchuen Global Birth Prevalence of Orofacial Clefts: A Systematic Review. J Med Assoc Thai: 2015, 98 Suppl 7;S11-21 PubMed 26742364
- Michael J Dixon, Mary L Marazita, Terri H Beaty, Jeffrey C Murray Cleft lip and palate: understanding genetic and environmental influences. Nat. Rev. Genet.: 2011, 12(3);167-78 PubMed 21331089
- Maynika V Rastogi, Stephen H LaFranchi Congenital hypothyroidism. Orphanet J Rare Dis: 2010, 5;17 PubMed 20537182 | Orphanet J Rare Dis.
- Luz Maria De-Regil, Ana C Fernández-Gaxiola, Therese Dowswell, Juan Pablo Peña-Rosas Effects and safety of periconceptional folate supplementation for preventing birth defects. Cochrane Database Syst Rev: 2010, (10);CD007950 PubMed 20927767
Indian J Plast Surg. 2009 October; 42(Suppl):Cleft Lip and Palate Issue Jeffrey O Bush, Rulang Jiang Palatogenesis: morphogenetic and molecular mechanisms of secondary palate development. Development: 2012, 139(2);231-43 PubMed 22186724
L Meng, Z Bian, R Torensma, J W Von den Hoff Biological mechanisms in palatogenesis and cleft palate. J. Dent. Res.: 2009, 88(1);22-33 PubMed 19131313
Marek Dudas, Wai-Yee Li, Jieun Kim, Alex Yang, Vesa Kaartinen Palatal fusion - where do the midline cells go? A review on cleft palate, a major human birth defect. Acta Histochem.: 2007, 109(1);1-14 PubMed 16962647
M W Ferguson Palate development. Development: 1988, 103 Suppl;41-60 PubMed 3074914
E D Hay An overview of epithelio-mesenchymal transformation. Acta Anat (Basel): 1995, 154(1);8-20 PubMed 8714286
Gerd Steding, Yutao Jian The origin and early development of the nasal septum in human embryos. Ann. Anat.: 2010, 192(2);82-5 PubMed 20149609
Wei Xiong, Fenglei He, Yuka Morikawa, Xueyan Yu, Zunyi Zhang, Yu Lan, Rulang Jiang, Peter Cserjesi, Yiping Chen Hand2 is required in the epithelium for palatogenesis in mice. Dev. Biol.: 2009, 330(1);131-41 PubMed 19341725
|Palate Development (expand to see terms)|
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- Prof Virginia Diewert - Professor of Orthodontics, University of British Columbia, who recently visited the Lab and helped with content, organisation and development of the Palate Development section.
- Medline Plus - Cleft Lip and Palate
- Better Health Channel - Cleft palate and cleft lip
- March of Dimes Birth Defects Foundation - Cleft Palate
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Cite this page: Hill, M.A. (2016) Embryology Palate Development. Retrieved October 25, 2016, from https://embryology.med.unsw.edu.au/embryology/index.php/Palate_Development
- © Dr Mark Hill 2016, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G