|Embryology - 29 Apr 2016 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
- Head Links: Introduction | Medicine Lecture | Medicine Lab | Science Lecture | Science Lab | Craniofacial Seminar | Palate | Tongue | Placodes | Skull Development | Head and Face Movies | Abnormalities | Category:Head
|1910 Skull | 1910 Skull Images | 1921 Human Brain Vascular | 1923 Head Subcutaneous Plexus | 1919 21mm Embryo Skull | 1920 Human Embryo Head Size | 1921 43 mm Fetal Skull | Historic Disclaimer|
Some Recent Findings
|More recent papers|
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.
Kanwalraj K Moar, Christopher Sweet, Victoria Beale Fistula Rate after primary palatal repair with intravelarveloplasty: a retrospective three-year audit of six units (NorCleft) in the UK. Br J Oral Maxillofac Surg: 2016; PubMed 27118617
Sinan Ozturk, Huseyin Karagoz, Fatih Zor, Gökhan Inangil, Kemal Kara Fetal cleft lip/palate surgery: End of a dream? Fetal Pediatr Pathol: 2016;1-5 PubMed 27115723
Claire Hamlet, Diana Harcourt Letter to the Editor. Older Adults' Experiences of Living with Cleft Lip and Palate: A Qualitative Study Exploring Ageing and Appearance. Cleft Palate Craniofac. J.: 2016; PubMed 27115563
Katherine Hixon, Lindsey Rhea, Jennifer Standley, Frank J Canady, John W Canady, Martine Dunnwald Interferon Regulatory Factor 6 Controls Proliferation of Keratinocytes From Children With Van der Woude Syndrome. Cleft Palate Craniofac. J.: 2016; PubMed 27115562
Asuka Kageyama-Iwata, Seiji Haraguchi, Seiji Iida, Tomonao Aikawa, Takashi Yamashiro Maxillary Anterior Segmental Distraction Osteogenesis to Correct Maxillary Deficiencies in a Patient With Cleft Lip and Palate. Cleft Palate Craniofac. J.: 2016; PubMed 27115561
Wojciech Bednarz, Christopher Kobierzycki, Piotr Dzięgiel, Ute Botzenhart, Tomasz Gedrange, Marek Ziętek Augmentation of the hard palate thin masticatory mucosa in the potential connective tissue donor sites using two collagen materials-clinical and histological comparison. Ann. Anat.: 2016; PubMed 26970501
Carlos Ibrahim, Crispian Scully Keep an eye out for the bifid uvula: yes please--as it is not always just an isolated congenital anomaly. Dent Update: 2015, 42(5);494 PubMed 26964455
Bartosz J Płachno, Małgorzata Stpiczyńska, Kevin L Davies, Piotr Świątek, Vitor Fernandes Oliveira de Miranda Floral ultrastructure of two Brazilian aquatic-epiphytic bladderworts: Utricularia cornigera Studnička and U. nelumbifolia Gardner (Lentibulariaceae). Protoplasma: 2016; PubMed 26945989
Samir A A Elgendy, Mohamed A M Alsafy, Mahmoud Tanekhy Morphological characterization of the oral cavity of the gilthead seabream (Sparus aurata) with emphasis on the teeth-age adaptation. Microsc. Res. Tech.: 2016; PubMed 26791335
Mahmood Khaksary Mahabady, Hossein Najafzadeh Varzi, Saeedeh Zareyan Jahromi L-Carnitine Protect against Cyclophosphamide Induced Skeletal and Neural Tube Malformations in Rat Fetuses. Acta Med Iran: 2015, 53(11);703-10 PubMed 26786992
- 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.
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
- 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
- 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.
- epithelial mesenchymal transition - (EMT, epitheliomesenchymal transformation) conversion of an epithelium into a mesenchymal (connective tissue) cellular organization.
- epitheliomesenchymal transformation - (epithelial mesenchymal transition) conversion of an epithelium into a mesenchymal (connective tissue) cellular organization.
- medial edge epithelial - (MEE) opposing palatal shelves adhere to each other to form this epithelial seam.
- 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.
- palatogenesis - The process of palate formation, divided into primary and secondary palate development.
- 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.
- 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)
- Transforming Growth Factor-beta - (TGFβ) factors induces both epithelial mesenchymal transition and/or apoptosis during palatal medial edge seam disintegration.
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.
- 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 April 29, 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