Face development and defects (face, jaws, palates, nose) 5. 5. 2021 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 Face development – Neural crest Doc. Petr Vaňhara Neuralcrest 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 Initiation Frontonasal prominence (processus frontonasalis) Paired prominences for upper jaw (processus maxillares) Paired 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 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 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 7th week Face development 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: upper lip In the middle of 7th week: processus nasalis lateralis (at both sides) fuse with the upper part of maxillary prominence Between 7th-8th week: the fusion of maxillary and mandibular processes: narrowing of rima oris Doc. Petr Vaňhara Face development - summary 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 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 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 suck 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 Rarely with the cleft of apex nasi Variable Critical period: 27. - 35. day The median cleft lip is one of symptoms of the Mohr syndrome Median cleft lip (labium leporinum) cheiloschisis mediana Oblique facial cleft (coloboma faciale, fissura orbitofacialis) Uni- or bilateral, arises if the nasolacrimal groove us preserved Combined always with the unilateral lip cleft and extends to the medial margin of the orbit Results from failure of the mesenchymal masses of the maxillary prominences to merge with lateral and medial nasal prominences rare 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 or „frog mouth“) Results from failure of the lateral parts of the maxillary and mandibular prominences to merge very rare 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 with each other Always connected with cleft of the mandible and tongue rare Treatment: a comprehensive approach (cleft teams) plastic surgeon, dentist - orthodontist, phoniatrist / anthropologist, event. psychologist 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 Begins at the 7th week Completed by the end of the 12th week The most critical period for the development of palate is from the beginning of 7th week to the beginning of 9th week 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 lateral palate processes are formed by mesenchyme, are covered by ectoderm a have shelf-like form (palatal shelves) Palatal shelves initially grow in caudal direction and laterally along to primordium of the tongue later, due more rapid vertical growth of mandibular processes the tongue descends caudally Palatogenesis During the 10th week shelves meet in the midline to finally fuse The site of fusion of both lateral palate processes is known as raphe palati Palatogenesis definitive palate originates by fusion of ventral edges of both lateral palatal shelves with the medial palate process Line of fusion corresponds to the incisive canal (canalis incisivus) The region of medial palate process (primary palate) and ventral parts of lateral palate processes undergo endesmal ossification The posterior portions of the lateral palate processes do not undergo ossification and give rise to the soft palate and uvula Palatogenesis Hard palate Primary palate Soft palate Secondary palate Palatogenesis • Primary palate (intermaxillary segment) • Secondary palate (lateral maxillary plates) Doc. Petr Vaňhara Horizontalizace a srůst patrových ploténekPalatogenesis Doc. Petr Vaňhara 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 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 Connection of nasal and oral cavities During the 5th week the oronasal membrane perforates via openings - the primitive choanae and both nasal sacs communicate to the stomodeum to form common mouth and nasal cavity (oronasal cavity, only for +-7 days) - see C Sagittal sections through nasal pit and stomodeum: Double-layered oronasal membrane (ectoderm of nasal cavity and stomodeum) Lower part of intermaxillar segment – philtrum Nose develops from 3 primordia simultaneously with development of face: 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 - grows from the intermaxilary segment in form of vertical plate, which fuses with lateral palate processes in the middle line (during 9-10th week) At the time of development of the septum, bases of conchae develop on the lateral wall of each nasal fossa (lower, middle and upper) After 13 week, the ectoderm covering roof of both nasal fossae transforms in the olfactory epithelium consisting of olfactory cells (unipolar neurons), whose axons constitute fila olfactoria The epithelium of sinuses is of the 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