Orofacial Embryology

1. Orofacial Embryology Prenatal Development

2. Websites to check out • http://www.bioscience.org/atlases/fert/htm/develhuman/fetdev.htm • http://embryology.med.unsw.edu.au/wwwhuman/stages/stage16.htm • http://www.visembryo.com/ • http://www1.umn.edu/dental/course/dent_5725/ • http://www.fleshandbones.com/readingroom/pdf/101.pdf • http://www.med.umich.edu/lrc/coursepages/M1/embryology/embryo/05embryonicperiod.htm

3. Fertilization & Development in Utero -fertilization in the upper third of the oviduct/fallopian tube -fertilization = union of egg and sperm -after fertilization = zygote -first period of prenatal development = preimplantation period -first week of development -development of the unattached zygote/embryo -immediately prior to the union of egg and sperm nuclei – the egg must complete the final stages of meiosis (meiosis I is completed as the egg primordium then stops) -fertilzation result in the combination of the haploid egg and sperm = diploid zygote -called an embryo once it begins to divide (within 24 hours) -division = mitosis

4. Embryonic terms to consider • induction • first process to occur during embryogenesis • interaction between developing embryonic cells • morphogenesis • may also be called morphodifferentiation • development of form and specific tissues • results from migration of embryonic cells and inductive interactions between these cells • patterning • specification of the embryo through segmentation • differentiation • process of specialization of embryonic cells • proliferation • controlled levels of mitosis • interstitial growth • growth deep within a tissue of organ • as opposed to appositional growth – growth at the periphery through the addition of additional cell layers

5. Prenatal development • 10 lunar months • three phases (first two = embryonic stage) • first – after fertilization and spans the first 4 weeks • largely cellular proliferation and migration • some differentiation • next 4 weeks of development • largely the differentiation of all major internal and external organs = morphogenesis • very vulnerable stage • remaining phase – fetal stage • largely a matter of growth and maturation

6. -preimplantation period – first week -embryonic stage - week 2 to week 8 OVIDUCT: -union of sperm and egg nuclei (zygote) -> first mitotic cell division (embryo) -> cell division continues -> formation of the morula UTERUS: -morula forms a blastocyst or blastula (assymetrical ball of cells with a cavity) -> implantation into the endometrium

7. -formation of the blastula marks the beginning of morphogenesis - shaping of the embryo, migration of dividing cells to specific locations -blastula = blastocyst - hollow ball of cells -outer layer = trophoblast - forms extraembryonic tissues (e.g. placenta, yolk sac) -inner mass of cells at one end - totipotent embryonic stem cells or embryoblasts

8. Second week of development • blastocyst increases in size by proliferation • a blastocoel or blastocyst cavity forms between the inner cell mass and the trophoblast • differentiation of the inner cell mass ES cells begins • results in the formation of a bilaminar embryonic disc comprised of two cell layers • two layers are called an upper epiblast (ectoderm, mesoderm, endoderm) and a lower hypoblast (extraembryonic endoderm) • above this disk is an upper amniotic cavity and a lower yolk sac (primitive hematopoietic organ for the embryo/fetus) • trophoblast also begins to differentiate to form a primitive placenta • the embryo connects to the developing placenta through a stalk

9. Third week of development • the bilaminar embryonic disk converts into a trilaminar • disk of ectoderm, mesoderm, endoderm (gastrulation) • formation of the primitive streak within the embryonic • disc critical to this formation • -migration of epiblast cells through the primitive streak • towards the hypoblast – eventually creates three tissue layers called the • germ layers • 1. ectoderm • 2. mesoderm • 3. endoderm humans are deuterostomes

10. Fourth week of embryonic development -portions of the mesoderm that do not form the notochord divide into sections called somites -> specific body regions and structures -38 somite pairs -give rise to most of the skeletal structures of the head, neck and trunk -by the end of the third week: trilaminar embryonic disc has a definite orientation -during the fourth week - embryo begins to form a tubular structure -in front of the primitive streak is the primitive node – mesodermal cells that will form the notochord -also have differentiation of cells from the ectoderm forms the neuroectoderm -a neural plate forms -this plate thickens with proliferation – invaginates centrally and forms the neural groove -this groove deepens and is surrounded by the two neural folds -development of the neural crest cells from these neural folds

11. Fourth week of embryonic development • the neural folds meet superior to the neural groove and forms the neural tube • neural folds also form the cells of the neural crest • migratory population of cells • multipotent • gives rise to ectodermal tissues and mesenchyme in specific areas of the head/face • embryo folds along this tube – results from extensive proliferation of the ectoderm and the differentiation of specific tissues at the cephalic end • the anterior end of the neural tube rapidly expands to form the beginnings of the forebrain, midbrain and hindbrain • also folds along the rostrocaudal axis • continued development of the somites

12. development of a head fold • is critical to the formation of the primitive oral cavity • folding results in the formation of the primitive oral cavity = stomatodeum • separated from the developing and expanding gut by a buccopharyngeal membrane (or oropharyngeal membrane)

13. the mesoderm can be divided into three distinct types • paraxial mesoderm • intermediate mesoderm • lateral plate mesoderm • the lateral folding determines the disposition of the germ layers • with lateral folding the amniotic cavity encompasses the entire embryo • the paraxial mesoderm remains adjacent to the developing neural tissue (induction) • the lateral plate mesoderm drops down and cavitates -the resulting cavity forms the coelom

14. Check out this site • http://php.med.unsw.edu.au/embryology/index.php?title=2010_Lecture_11#Animation_of_Face_Development

15. Head formation • rostral or head fold • anterior portion of the neural tube expands as the forebrain, midbrain and hindbrain • the neuroectoderm in this region will form the olfactory, orbital and otic placodes • the hindbrain forms 8 bulges = rhombomeres • the paraxial mesoderm in this region also segments into somites • migration of neural crest cells into this region provides the embryonic connective tissue (mesenchyme) required for development of the craniofacial structures • these neural crest cells arise from the midbrain and the first two rhombomeres as two streams

16. Branchial arches • also called pharyngeal arches • figure 4-11 • fourth week: development of a frontal prominence forms the stomatodeum • below this is the formation of the first branchial arch (mandibular arch) • 6 pairs – U shaped • core of mesenchymal tissue formed from neural crest cells that migrate in to form the arches • covered externally by ectoderm and lined internally by endoderm • each has its own developing cartilage, nerve, vascular and muscular components • these arches separate the stomatodeum from the developing heart

17. Branchial arches • separated laterally by branchial grooves/clefts • medially they are separated by pharyngeal pouches • first arch (mandibular arch) – maxillary and mandibular processes • second arch (hyoid arch) - hyoid bone, part of the temporal bone (VII nerve) • cartilage = Reichert’s cartilage • the mesoderm of this arch will form the muscles of facial expression, the middle ear muscles • third arch –tongue (IX nerve) • fourth arch –tongue, most of the laryngeal cartilages (IX and X nerves) • fifth arch – becomes incorporated into the fourth • sixth arch – most of the laryngeal cartilages (IX and X nerves)

18. Pharyngeal Pouches • four well-defined pairs of pharyngeal pouches develop from the lateral walls of the pharynx • first pouch (betwen the 1st and 2nd arches) - external acoustic meatus, tympanic membrane, and eustachian tube • second pouch – palatine tonsils • third pouch - thyroid and parathyroid glands, • fourth pouch – parathryoid gland • fifth pouch -becomes incorporated into the fourth

19. Development of the Face • forms from the fusion of 5 face primordia which develop during week 4 and fuse during weeks 5 through 8 • primordia = ectodermal swellings or prominences that are filled with mesodermal and neural crest cells • frontonasal prominence • mandibular prominences (2) – from branchial arch #1 • maxillary prominences (2) – from branchial arch #1

20. Development of the Face MOVIE http://www.indiana.edu/~anat550/hnanim/face/face.html

22. Stomatodeum • primitive stomatodeum forms a wide shallow depression in the face – limited in its depth by the buccopharyngeal membrane

23. Development of the Upper Face • within the fourth week (weeks 5 – 8) • the frontonasal prominence develops two sets of placodes (nasal and lens) • formation is dominated by the proliferation and migration of ectomesenchyme cells • MAJOR EVENTS • development of medial and lateral nasal processes or swellings which encircle the nasal pits • fusion of the medial nasal processes at the midline = intermaxillary/premaxillary process or process • formation of the upper portion of the face is faster than the lower portion (finally cease to grow at puberty) MOVIE http://www.indiana.edu/~anat550/hnanim/face/face.html

24. Development of the Upper Face • rapid proliferation of the underlying mesenchyme around the placodes results in bulges in the frontal eminence and produces a horseshoe-shaped ridge in each olfactory placode • medial and lateral nasal processes • in between the medial nasal processes is where the nose develops = called the frontonasal prominence • the medial nasal processes of both sides + the frontonasal prominence give rise to the middle portion of the nose, upper lip, anterior portion of the maxilla and the primary palate • the medial nasal processes also fuse internally and form the premaxillary segment • the frontonasal prominence will also form part of the forehead

25. Development of the Upper Face • day 24: development of the frontal prominence (covers the rapidly expanding forebrain) • beginnings of the mandibular and maxillary processes from the 1st branchial arch • well-defined boundaries of the stomatodeum results • day 26: well-formed maxillary and mandibular processes • day 27: appearance of the nasal placode and the odontogenic epithelium • day 28: localized thickenings develop within the frontal prominence = olfactory placodes

26. Upper lip formation • during the fourth week • fusion of the maxillary processes with each medial nasal process • this contributes to the lateral sides of the upper lip – together with the medial nasal processes which contribute to the medial aspect of the upper lip • the maxillary processes also fuse with the lateral nasal processes – results in a nasolacrimal groove which extends from the medial corner of the eye to the nasal cavity

27. Development of the Palate • involves the formation of a primary palate, a secondary palate and fusion of their processes • Primary palate • forms from an internal swelling of the intermaxillary/premaxillary process (fusion of medial nasal processes) • Secondary palate • forms from the two lateral palatine shelves or processes • develop as internal projections of the maxillary prominences

28. Primary palate • fusion of the median nasal processes gives rise to the median palatine process – fuses to form the primary palate MOVIES http://www.indiana.edu/~anat550/hnanim/face/face.html

29. Secondary Palate • the common oronasal cavity is bounded anteriorly by the primary palate and occupied by the developing tongue • only after the development of the secondary palate can oral and nasal cavities by distinguished • three outgrowth appear in the oral cavity • nasal septum: • grows downward through the oral cavity • it encounters the primary and secondary palates • two palatine shelves • closure of the secondary palate is likely to involve the hardening of the palatine shelves – mechanism remains unknown + the withdrawl of the tongue

30. Palatine shelves

31. Cleft lip and palate

32. Nose • complex combination of contributions of the frontal prominence (forms the bridge), the merged medial nasal prominences (form the median ridge and tip of nose), the lateral nasal prominences (form the alae) and the cartilage nasal capsule (forms the septum and the nasal conchae) • the external nasal region develops from the superficial alar field – gives rise to the alae • Nasal pits and cavities • separate anteriorly from the stomatodeum by fusion of the medial nasal, lateral nasal and maxillary prominences – form the nostrils • separate posteriorly from the stomatodeum by the oronasal membrane • the developing nasal cavities are separated from the oral cavity by the intermaxillary process (forms the floor of the nasal cavity) • Nasal capsule and nasal septum • condensation of the mesenchyme within the frontonasal prominence – forms the precartilagenous nasal capsule • the capsule develops as two masses around the nasal cavities • the median mass becomes the progenitor of the nasal septum • the lateral masses will form the conchae and nasal alar cartilages

33. nasal cavity • early development of the face is dominated by the proliferation and migration of tissue involved in the formation of the primitive nasal cavities • about 28 days localized thickenings develop within the primitive ectoderm of the embryo – olfactory placodes • rapid proliferation of the underlying mesenchyme around the placodes bulges the frontal eminence forward and produces the nasal pit • the lateral arm of this pit = lateral nasal process • the media arm = medial nasal process • in between these nasal pits is the frontonasal process – where the nose develops • the two medial processes + the frontonasal give rise to the medial portion of the nose and upper lip, the anterior portion of the maxilla and palate

34. Nasal and Paranasal tissues • nasal cavity lined with a respiratory mucosa like the rest of the respiratory system • pseudostratified columnar epithelium with cilia • interspersed are goblet cells which rest on the basement membrane • very vascular lamina propria – warms the air • roof of the nasal cavity is a specialized area that contains the olfactory epithelium • on the medial wall are the three nasal conchae • paranasal sinuses • frontal, sphenoid, maxillary and ethmoid sinuses • provide mucus for the nasal cavity • respiratory mucosa of ciliated pseudostratified columnar epithelium • but is thinner than the nasal mucosa – also has fewer goblet cells • no erectile tissue

35. Development of Sinuses and Nasal cavity • paranasal sinuses • some develop during late fetal life • frontal and sphenoid not present at birth • at 2 years the two most anterior ethmoid sinuses grow into the frontal bone – visible on X-rays by age 7 • two most posterior ethmoid sinuses grow into the sphenoid bone • sinuses are important in the size and shape of the face during infancy and the resonance of the voice • the rest develop after birth • form as outgrowths of the wall of the nasal cavity • become air-filled extensions in the adjacent bones • the original openings of these outgrowths persist as the orifices of the adult sinuses

36. Maxilla formation • centers of ossification develop in the mesenchyme of the maxillary processes of the first branchial arch • spreads posteriorly below the orbit towards the developing zygoma and anteriorly toward the future incisor region and superiorly to form the frontal process • ossification also spreads into the palatine process to form the hard palate • at the union between the palatal process and the main body of the developing maxilla is the medial alveolar plate – together with the lateral plates – development of the maxillary teeth • a zygomatic or malar cartilage appears in the developing zygomatic processes and contributes to the development of the maxilla

37. Development of the Lower Face • within the fourth week • two bulges form inferior to the stomatodeum

38. Mandible formation • the cartilage of the first branchial arch associated with the formation of the mandible = Meckel’s cartilage • 6 weeks: Meckel’s cartilage forms a rod surrounded by a fibrocellular capsule • the two cartilages do not meet at the midline but are separated by a thin line of cartilage = symphysis • on the lateral aspect of this symphysis – a condensation of mesenchyme forms • at 7 weeks intramembranous ossification begins in this mesenchyme and spreads anteriorly and posteriorly to form the bone of the mandible • the bone spreads anteriorly to the midline of the developing lower jaw – the bones do not fuse at the midline – mandibular symphysis forms (from meckel’s cartilage) • which fuses shortly after birth • the ramus develops from rapid ossification posteriorly into the mesenchyme of the first arch

39. Mandible formation -Meckel’s cartilage does NOT contribute directly to the ossification of the mandible -posterior extremity – malleolus of the inner ear -portion persists as the sphenomandibular ligament -significant portion is resorbed entirely -most anterior portion near the midline may contribute to the jaw through endochondral ossification -growth of the mandible until birth is influences by the appearance of three secondary (growth) cartilages 1. condylar – 12th week, developing ramus by endochondral ossification, a thick layer persists at birth at the condylar head (mechanism for post-natal growth of the ramus = endochondral) 2. coronoid – 4 months, disappears before birth 3. symphyseal – appears in the connective tissue at the ends of the Meckel’s cartilage, gone after 1 year after birth

40. Development of the Tongue • begins to develop about 4 weeks • localized proliferation of the mesenchyme results in formation of several swellings in the floor of the oral cavity • the oral part (anterior two-thirds) develops from the fusion of two distal tongue buds or lateral lingual swellings and a median tongue bud (tuberculum impar) • the pharyngeal part or root of the tongue (posterior one-third) develops from the copula and the hypobranchial eminence (forms from the 2nd, 3rd and 4th branchial arches) • these parts fuse (adult = terminal sulcus) • muscles of the tongue arise from occipital somites which migrate into the tongue area B.As #1,2 and 3 hypobranchial arch overgrows the 2nd arch MOVIE: http://php.med.unsw.edu.au/embryology/images/8/88/Tongue.gif