Face development and defects (face, jaws, palates, nose) 17. 4. 2024 Jan Křivánek Body segmentation Body segmentation Body segmentation – is a human body segmented? The same segmentation pattern as in a primitive species The same signalling pathways We are the result of minor changes in signalling pathways and its final tuning Neuralcrest Face development – Neural crest Doc. Petr Vaňhara https://www.youtube.com/watch?v=1zpV5rzWXMA&ab_channel=GetAnimatedMedical Development from zygote https://www.youtube.com/watch?v=FhhWG3XzARY&ab_channel=FacultyofDentistry%2CUniversityofToronto Face development https://www.youtube.com/watch?v=iLbqzTlZ6yA&ab_channel=Osmosis • 5 mm embryo appears as Carnegie Stage 13 from ectopic pregnancy. • Week 4-5, 26 - 30 days, 3 - 5 mm, Somite Number 21 - 29 • Ectoderm: Neural tube continues to close, Caudal neuropore closes, forebrain • Mesoderm: continued segmentation of paraxial mesoderm (21 - 29 somite pairs), heart prominence • Head: 1st, 2nd and 3rd pharyngeal arch, forebrain, site of lens placode, site of otic placode, stomodeum • Body: heart, liver, umbilical, early upper limb bulge By the end of 1st month, the embryo has a form of short tube C-shaped curved dorsal side of embryo is convex and adjacent to amnion, cephalic end of the embryo is more advanced in development than caudal one Body parts: head, neck, body and tail Length of the embryo is 8 -10 mm Frontal prominence with prosencephalon Mesencephalic prominence with mesencephalon - flexura cephalica Occipital prominence with rhombencephalon - flexura occipitalis Human fetus at the end of 1st month of development Pharyngeal (branchial) aparatus: 6 Branchial arches 4 Branchial clefts (grooves) (ectodermal) 5 Branchial pouches (entodermal) Separated by membranae obturantes Human fetus at the end of 1st month of development Branchial aparatus Doc. Petr Vaňhara 1. Pharyngeal arch (mandibular) is divided into : - Processus maxillaris - Processus mandibularis Branchial aparatus Doc. Petr Vaňhara By the end of 4th week of development the face development is initiated around the primitive mouth opening: stomodeum The oral cavity develops from the stomodeum or primitive mouth Bottom of the stomodeum is constituted by oropharyngeal membrane (membrana oropharyngea) Development is organized by 2 centers: - Prosencephalic - Rhombencephalic 5 processes limit the stomodeum: - Frontonasal prominence - Paired maxillary prominences (processus maxillares) - Paired mandibular prominences (processus mandibulares) The base of the prominences is formed by an ectomesenchyme, which populated them from the lower mesencephalic and upper rhombencephalic section of the neural crest. The surface of the prominences is covered by an ectoderm, which also lines the stomodeum. Prominences are initially separated from each other by deep grooves. It is a dynamic process - it starts at the end of the 4th and beginning of 5th week of development and ends at about the 8th week. It depends on the proliferation of the ectoderm and ectomezenchyme of the prominences and their further divisions, movements and different growth rates. It is terminated by the fusion of the protrusions. Face development Face development Doc. Petr Vaňhara Frontonasal prominence (processus frontonasalis) Paired prominences for upper jaw (processus maxillares) aired prominences for lower jaw (processus mandibulares) Face development Face development processus maxillares processus mandibularis nasal placode stomodeum 2. Pharyngeal arch processus frontonasalis stomodeum Doc. Petr Vaňhara Face development 4th week Doc. Petr Vaňhara • Nasal pits surrrounded by paired prominences – medial and lateral nasal prominence • Area triangularis (nose) • Intermaxilary segment (medial part of upper lip, part of upper jaw, primary palate) Face development Doc. Petr Vaňhara Frontonasal prominence (gives rise to forehead, nose and middle part of upper lip - philtrum) After the formation of nasal pits the ectomesenchyme is divided into parts: Processus nasalis medialis Processus nasalis lateralis Triangular area between medial nose processes is called area triangularis By the end of the 5th week, the medial nasal prominences fuse with each other to form the intermaxillary segment The segment proliferates caudally and inserts between ends of maxillary prominences which merge with it during the 6th week The intermaxillary segment gives rise to: a) middle portion of the upper lip, or philtrum b) the premaxillary part of the maxilla c) the primary palate The common upper lip is formed after the intermaxillary segment has fused with the maxillary processes At first, lateral nasal prominences are separated from the maxillary prominences by a furrow, called the nasolacrimal groove During next days, the maxillary prominences enlarge and fuse with lateral nasal prominences. Intermaxillary segment Face development Maxillary prominences fuse with: 1. Intermaxillar segment (formation of upper lip and palate) 2. Lateral nasal prominences (the rest of upper lip and part of nose) Lateral nasal prominences are divided from the maxillary prominences by - sulcus nasolacrimalis Doc. Petr Vaňhara Summary of face development timing Between 5. - 7. week Beginning of 5th week: fusion of medial edges of mandibular prominences: lower lip and chin Beginning of 6th week: fusion of medial edges of maxillary prominences with intermaxillary segment: common upper lip In the middle of 7th week: processus nasalis lateralis (at both sides) fuse with the upper part of maxillary prominence – the nasomaxillary groove disappears Between 7th-8th week: the fusion of maxillary and mandibular processes: narrowing of rima oris Doc. Petr Vaňhara Face development Shh a FGF Doc. Petr Vaňhara Face development – Shh (Sonic Hedgehog) Doc. Petr Vaňhara Normal Cyclopamine (teratogen) anti-SHH Ab Face development Doc. Petr Vaňhara Orofacial clefts Clefts of the upper lip Median clefts of the lower lip and chin (mandible) Oblique facial clefts Lateral, or transverse, facial clefts When the processes fuse, the basis of the brain, in particular the telencephalon, grows rapidly and so does the neurocranium The originally laterally oriented eyes shift forward. By the end of the second month, the embryo's face already shows characteristic human features Clefts emerge when the development of prominences was incorrect: prominences did not fuse, were not established, belated migration or proliferation Facial clefts belong to the most common developmental defects Incidence: 1,7 : 1 000 newborns Lateral or medial Lateral: • Unilateral cleft lip - results from failure of maxillary prominence to merge with the lateral edge of intermaxillary segment on the one side • Bilateral cleft lip - results from failure of mesenchymal masses of both maxillary prominences to merge with lateral edges of intermaxillary segment cheiloschisis unilateralis / cheiloschisis bilateralis Clefts of the upper lip - cheiloschisis superior Bilateral clefts of the lip and maxilla are very hard defect Clefts can be uni and bilateral The child can not be fed and is in danger of aspiration of food (Bi)lateral clefts of the lip and palate Is caused by delay in development of intermaxillary segment due failure of the medial nasal prominences (processus nasales mediales) to merge Delay in the development of the intermaxillary segment Rarely with the cleft of apex nasi Variable extent Isolated or in combination with facial skeletal clefts Critical period: 27. - 35. day The median cleft lip is one of symptoms of the Mohr syndrome Median cleft lip – cheiloschisis mediana Oblique facial cleft (coloboma faciale, fissura orbitofacialis) The processus maxillaris is not fused with the processus nasalis medialis (intermaxillary segment) and the processus nasalis lateralis Oculonasal groove is preserved Uni- or bilateral Rare incidence Lateral/transverse facial cleft fissura transversa faciei, macrostomia Runs from the mouth toward the ear Bilateral clefts results in a very large rima oris (macrostomia) Results from failure of the lateral parts of the maxillary and mandibular prominences to merge Rare incidence Median cleft of the lower lip and chin (mandible) cheiloschisis et gnathoschisis inferior Cleft resulting from failure of the mesenchymal masses of the mandibular prominences to merge completely Always connected with cleft of the mandible and tongue Rare incidence Treatment: a comprehensive approach (cleft teams) plastic surgeon, dentist - orthodontist, phoniatrist / anthropologist, event. psychologist Pediatrician's recommendation: 1) plastic surgery examination no later than 2 months after birth 2) for simple cleft lip - cheiloplasty: 2nd - 5th month 3) cleft lip combined with lateral cleft of the jaw and primary palate: treated between 2 and 4 years 4) between 12 - 18 months: phoniatric examination + possibly speech therapist 5) orthodontic care - replacement of missing teeth Oral cavity develops from the stomodeum or primitive mouth 5 processes limit the stomodeum: frontonasal prominence paired maxillary prominences (processus maxillares) paired mandibular prominences (processus mandibulares) on sides Stomodeum communicates with the body surface via primitive oral entrance Bottom of the stomodeum - oropharyngeal membrane (membrana oropharyngea) When the oropharyngeal membrane ruptures, the stomodeum becomes continuous with the foregut Roof of the stomodeum consists of a mesenchyme and ectoderm of the frontonasal prominence * Development of oral cavity membrana oropharyngea connection of the nasal passages to the stomodeum They are separated by a two-layered epithelial septum - the ectoderm of the nasal canal and the ectoderm of the stomodeum oronasal (bucconasal) membrane When the membrane perforates (end of 5 week), the nasal canals open into the stomodeum through an opening - primitive choana common oral and nasal cavity (oronasal cavity) approx. 7 days In the middle of the 6th week, the oronasal cavity begins to split with the horizontal septum into the definitive nasal cavity and oral cavity Begins at week 6, ends at about week 12 (the fusion of uvula) 3 primordia: Unpaired medial palate process and paired lateral palate processes (palatal shelves) a) The medial palate process Grows from the dorsal side of the intermaxillary segment at the end of the 5th week and gives rise to primary palate Palatogenesis b) Lateral palate processes - grow out from medial aspects of the maxillary prominences and give rise to the secondary palate (end of 6th week) The palatal plates initially grow caudally (on the sides of the base of the tongue), at the end of the 7th week they rise to the horizontal position of "horizontalisation of the palatal plates" (caudal descent of the tongue caused by the vertical growth of the mandibular processes), the medial ends of the plates grow opposite each other - at the beginning of the 8th week they meet anteriorly. Palatogenesis During the 12th week, palatal fusion is completed at the site of the uvula The site of fusion of both lateral palate processes is known as raphe palati Palatogenesis At the same time, the anterior edges of the lateral palatal plates fuse with the unpaired medial plate - single palate Foramen incisivum opens in the line of growth of all three parts The mesenchyme of the primary palate and the secondary palate (except for a short dorsal section) then ossify (intramembranous) and the palate is differentiated into: Hard palate - palatum durum Soft palate - palatum molle and uvula Palatogenesis Hard palate Primary palate Soft palate Secondary palate Can be of isolated character or associated with clefts of the and upper lip Complete or incomplete unilateral or bilateral The incidence of palate clefts is 1 : 2500 live births 1/5 genetic background Clefts of primary palate (C, D) clefts of both primary and secondary palate (E) clefts of secondary palate (F) Palate clefts Anteriorly to the incisive foramen The primary and secondary palates are separated Results from failure of fusion of lateral palatal shelves with the primary palate Unilateral/bilateral Clefts of primary palate (C,D) Clefts of both primary and secondary palates (E) Both anteriorly and posteriorly to the incisive foramen Lateral palate processes are not fused and separated from the primary palate The nasal septum is free Usually associated with lateral cleft of the maxilla and upper lip cheilognathopalatoschisis unilateralis / bilateralis (very serious malformation) Posteriorly to the incisive foramen Cause: lateral palatine processes do not fuse Affect the all sections of palate (hard, soft and uvula staphyloschisis / uvula bifida) Clefts of the secondary palate occur more frequently in females than males (3:2) Pierre-Robin syndrom: cleft of palate, hypoplasia of the lower jaw, glossoptosis and pseudomacroglosia - malformation with recessive inheritance bound to the X chromosom Clefts of secondary palate (palatoschisis) Staphyloschisis (uvula bifida) – rozštěp uvuly Critical period in palatogenesis: 37. - 53. day (cleft of primary or both palates) 53. - 57/58. day (cleft of secondary palate) Prediction of clefts (in general) Healthy parents having child with cleft: 2% probability of the cleft of the second child 7% probability of the cleft (if both has cleft) One parent had cleft and child with cleft is born 15% probablity of the cleft of the next child Oral vestibule develops from the labiogingival lamina (vestibular lamina) Emerges during the 6th week Thickened area of the ectoderm, fast proliferation of ectoderm against mesenchymal core of prominences that delineate the stomodeum Cells in the center of lamina then undergo apoptosis - labiogingival groove is established Ventral section - the definitive lip Dorsal section - the gingival ridge (torus) Oral vestibule development Maxilla Paired bone, intramembranous ossification Fusion of 3 parts: Frontal part of the bone with incisors (intermaxilla) - intermaxillary segment Lateral parts of the bone - both maxillary prominences (processus maxillares) Lateral parts fuse to the frontal segment in incisive suture (sutura incisiva) on both sides Ossification begins between 6 - 8 week maxilla in newborns is shallow because has not formed alveolar processes yet (developed during the eruption of deciduos dentition) Development of maxilla and mandible Mandible develops partly by intramembranous, partly by intracartilaginous ossification Body of mandible and both ramus of mandible are of intramembranous origin (for ossification is used mesenchyme located anterolateral to the Meckel cartilage that support the mandibular prominences Ossification begins in the 6th week. Condyle and coronoid process develop by intracartilaginous ossification (condyle between 12 - to 20 weeks, coronoid process yet later) Lower jaw of neonates is low and its development continues in postnatal period The angle between ramus and body of mandible continual reduces (from 140-150 to 120 for adult) Development of maxilla and mandible Nosal placodes → Nasal pits → Nasal sacs, grows dorsocaudally to roof of stomodeum, from which are initially separated by the oronasal membrane lens Nasal cavity Lower part of intermaxillar segment – philtrum Middle and upper part of the intermaxillary segment - gives rise to the apex Lateral nasal processes give rise to Dorsum et radix nasi, alae nasi All primordia rapidly proliferate ventrally and nose protrudes (firstly flattened structure) Nose development Septum nasi (9th week) - grows from the intermaxilary segment in form of vertical plate, which fuses with lateral palate processes in the middle line The ventrocranial and dorsocaudal section of the septum intramembraneusly ossifies giving rise to the lamina mediana ossis ethmoidis and vomer, the remaining part forms the cartilaginous part of the septum. At the time of development of the septum, bases of conchae develop on the lateral wall of each nasal fossa (lower, middle and upper) Vývoj nosu a nosních dutin After the 13th week, the ectoderm of nasal cavity differentiates into olfactory epithelium Between 13 and 15 weeks, the nostrils are closed by epithelial plugs Opening (recanalization) occurs in the 6th month Paranasal sinuses (sinus paranasales) are the last to form (at the end of the fetal period) - they are the protuberances of the definitive wall of the nasal cavity: - sinus maxilaris - already present at birth - sinus ethmoidalis - around the 2nd year - sinus frontalis and sphenoidalis - between 4 and 6 years The epithelium of the nasal cavity and sinus epithelium is of ectodermal origin Vývoj nosu a nosních dutin Defects are of rare occurrence Occur separated or in association with anomalies of the upper lip and jaw or whole face Aplasia (agenesis) of the nose - caused by lack of nasal placodes Hypoplasia of the nose - a small nose with a single cavity combined with micrognathy Nasoschisis (nares bifides) - median cleft of the nose - caused by non-fused medial nasal prominences The extent of cleft is variable - from shallow groove on the nose apex to the complete duplication of the nasal septum Developmental defects of the nose Atresia introitus nasi (vestibuli nasi) - vestibulum nasi is closed by thin funnel shaped membrane (caused of persistence of epithelial plugs, which obturate nostrils of the fetus in the 3rd month) Atresia choanarum – choana is closed with connective tissue membrane or bone plate persistence of the oronasal (buconasal) membrane 1: 10 000 autosomal dominant inheritance Other defects: nasus duplex (rhinodynia), proboscis Veratrum californicum http://www.sci-news.com/othersciences/anthropology/newborn-babies-skills-pick-out-individual-words-06863.html