2. MECHANISMS OF DEVELOPMENT 1 Cells proliferate to: Increase a cell mass, to cover a growing surface, or to create or increase the stratification of a layer or structure Cells differentiate to specialized forms, e.g., mesenchymal cells to osteoblasts & cementoblasts Cells migrate to new positions ,e.g., neural crest cells Cells produce extracellular materials: fibers, matrix, cuticle, etc Cell die by apoptosis and/ or digest their surroundings , so that some structures regress in size and disappear, e.g., Meckel’s cartilage, Hertwig’s root sheath Differential growth of tissues, e.g., mesenchyme growing more than overlying ectoderm to yield protrusions or ridges, with clefts in between them GENERAL

3. MECHANISMS OF DEVELOPMENT 2 Differential growth of tissues, e.g., mesenchyme growing more than overlying ectoderm to yield protrusions or ridges, with clefts in between them ECTODERM MESENCHYME Mesenchyme has grown more & unevenly Surface is greater so that some ectodermal proliferation must have occurred Basal lamina is important, but not shown GENERAL

4. GENERAL MECHANISMS OF DEVELOPMENT 3 Fate of clefts between ridges: (i) the cleft may deepen by further growth in the bulges; (ii) the cleft may be eradicated by disproportionate growth beneath it

5. MECHANISMS OF DEVELOPMENT 4 Fate of clefts between ridges: (iii) the cleft may be bridged or covered over to form a duct-like structure, e.g., groove becoming a duct Fusion mark most growth GENERAL

6. MECHANISMS OF DEVELOPMENT Figs show that: (I) the duct thus formed is lined by ectoderm; (ii) the ectodermal cells (& endodermal) can attach to each other when meeting cells approaching from another direction This kind of fusion is very important in development GENERAL Fusion

7. MECHANISMS OF DEVELOPMENT 5 Fate of clefts between ridges: (iv) base of the cleft forms a cord that separates, then is canalized -- constructs a tube , e.g., to form the nasolacrimal duct Fusion Cord canalizes Loss of connection GENERAL Proliferation a cord of cells

8. GENERAL MECHANISMS OF DEVELOPMENT 6 Fate of fused ectoderm I Creation of epithelial diaphragm Creation of epithelial diaphragm Which may later disappear, e.g., bucconasal membrane

9. MECHANISMS OF DEVELOPMENT 7 Fate of fused ectoderm II Penetration of dissolving fused ectoderm by mesenchyme E.g., fusion of palatal processes GENERAL

10. MECHANISMS OF DEVELOPMENT 8 Fate of fused ectoderm II Penetration of dissolving fused ectoderm by mesenchyme Mesenchyme later becomes bone & CT Some ectodermal cells become mesenchymal - an epithelio-mesenchymal conversion Others die by apoptosis GENERAL

11. MECHANISMS OF DEVELOPMENT 9 Downgrowth of ectoderm into mesenchyme Relies on an INDUCTIVE exchange of chemical messages between mesenchyme and ectoderm Mitotic area BUD CORD e.g., for gland or hair follicle LAMINA (sheet) e.g., dental or bucco-labial OR GENERAL

12. MECHANISMS OF DEVELOPMENT 10 Ectodermal laminae can be used: LAMINA At discrete points only , for making dental organs of tooth germs. The remainder of the lamina then breaks up and disappears, but a few ectodermal cells may remain as epithelial rests or pearls The whole sheet may split to form a furrow lined by ectodermal epithelium on both sides, e.g., formation of vestibule from bucco-labial/vestibular lamina Split Split involves loss of cell-cell adhesion, apoptosis & continued proliferation GENERAL

13. The whole sheet may split to form a furrow lined by ectodermal epithelium on both sides, e.g., formation of vestibule from bucco-labial/vestibular lamina Split involves loss of cell-cell adhesion, apoptosis & continued proliferation GENERAL Split

14. MECHANISMS OF DEVELOPMENT 11 Ectodermal cells can differentiate Cord cells into DUCT & SECRETORY cells within a gland Dental organ cells into outer epithelium, inner epithelium, stellate reticulum, & stratum intermedium cells TOOTH GERM DENTAL LAMINA Outer dental epithelium Stellate reticulum Inner dental epithelium Stratum intermedium GENERAL Stroma

15. MECHANISMS OF DEVELOPMENT 12 Fate of diffferentiated cells (N ot confined to ectodermal cells) Might go back to a less active/differentiated state, e.g., cementoblasts to resting cementoblasts May remain as they are, e.g., odontoblasts May be resorbed or commit suicide/ apoptosis , e.g., root sheath cells May fuse with other cells and lose their identity, e.g., reduced dental epithelium fuses with the gingival epithelium in eruption GENERAL

16. CARDIAC BULGE Remains of FRONTONASAL PROMINENCE after development of nasal placodes OPTIC PLACODE NASAL PLACODE MAXILLARY PROCESS MANDIBULAR ARCH HYOID ARCH STOMODEUM with perforating membrane 4-w/3.5mm EMBRYO Full-face FACE

17. FACIAL DEVELOPMENT 1-7 wks The slides to follow cannot convey the increase in size involved First shown is the external story of the face, but this will be matched in subsequent slides by the internal oral developments for tongue, palate, etc The change is continuous so that the Figs represent a just few ‘baby pictures’ as the elaborate events unfold FACE

18. FACIAL DEVELOPMENT 1-7 wks At each ‘stage’ be able to analyze the view for its parts, and for what will happen to each part in transforming to the next ‘stage’ The change is continuous so that the Figs represent a just few ‘baby pictures’ as the elaborate events unfold Stories for face, nasal cavity, palates, jaws & teeth, & tongue FACE

19. FRONTONASAL PROMINENCE Brain developing behind NASAL & OPTIC PLACODES thickenings of ectoderm MANDIBULAR ARCH formed by early fusion of mandibular processes STOMODEUM oral depression - part that did not grow forward - with bucco/oro-pharyngeal membrane at bottom 4-w/3.5mm EMBRYO Full-face FACE CARDIAC BULGE

20. OPTIC PLACODE NASAL PLACODES are prime movers CARDIAC BULGE deepen to form NASAL PITS defi ning lateral from medial nasal processes These move medially allowing maxillary processes to move from sides of head to a frontal position & allowing eyes to move from sides to a more frontal position Lateral processes will become alae of nose Medial processes form midline nose & contribute to lip, central upper jaw & primary palate 4-w/3.5mm EMBRYO FACE

21. CARDIAC BULGE 5.5-w/9mm EMBRYO Stomodeum FACE OLFACTORY/NASAL PIT EYE NASOMEDIAL PROCESS NASO-OPTIC GROOVE MANDIBULAR ARCH HYOID ARCH MAXILLARY PROCESS

22. 5.5-w/9mm EMBRYO NASOLATERAL PROCESS NASO-OPTIC GROOVE or furrow between lateral-nasal & maxillary processes will later be covered over to form part of the nasolacrimal duct MAXILLARY PROCESS Stomodeum FACE

23. 5.5-w/9mm EMBRYO NASOMEDIAL PROCESS MAXILLARY PROCESS grow to meet just off the midline, which is occupied by the fusing medial nasal processes & FACE FRONTONASAL REGION gets squeezed back by merging nasomedial processes

24. 7-w/19mm EMBRYO EAR TUBERCLES EYE FOREHEAD MOUTH LOWER JAW HYOID BONE MAXILLARY PROCESS LARYNGEAL CARTILAGES FACE

25. 7-w/19mm EMBRYO EAR TUBERCLES Ear will move posteriorly FOREHEAD bulges forward as brain enlarges MOUTH MAXILLARY PROCESS Joining of maxillary processes & mandibular arch moving medially reduces width of the mouth & contributes to cheek LOWER JAW FACE

26. 7-w/19mm EMBRYO becomes INTER-MAXILLARY SEGMENT (i) Philtrum of lip (ii) Upper jaw region carrying 4 incisor teeth (iii) Triangular primary palate FACE

27. INTERMAXILLARY SEGMENT Sagittal cut BRAIN PHILTRUM of LIP PRIMARY PALATE LIP 4-INCISOR MAXILLA = INTER-MAXILLARY SEGMENT 1 2 3 PALATE

28. MATURE FACE: Sources FRONTONASAL PROMINENCE OPTIC PLACODE NASAL PLACODE central part inside as olfactory mucosa MAXILLARY PROCESS MANDIBULAR ARCH HYOID and STOMODEUM NASOMEDIAL PROCESS NASOLATERAL PROCESS NASAL PIT MANDIBULAR ARCHES FACE

29. FACE FACIAL DEFECTS: Developmental OBLIQUE FACIAL CLEFT MEDIAN CLEFT JAW UNILATERAL MACROSTOMIA mouth too wide (microstomia - too small) MEDIAN CLEFT LIP Nose may also be cleft UNILATERAL CLEFT LIP

30. FACIAL DEFECTS: Failures of processes to fuse OBLIQUE FACIAL CLEFT MEDIAN CLEFT JAW UNILATERAL MACROSTOMIA MEDIAN CLEFT LIP UNILATERAL CLEFT LIP Mandibular & Maxillary Maxillary & Nasolateral Nasomedial & Nasomedial Mandibular & Mandibular Maxillary & Nasomedial FACE

31. FACIAL DEVELOPMENT 1-7 wks MOSTLY BY ALTERING PROPORTIONS FACE

32. CHEEK HAIRY SKIN BUCCAL MUCOSA thick strat squam ep BUCCAL GLAND mucous MUSCLE ADIPOSE TISSUE MUSCLE Buccinator CONNECTIVE TISSUE GENERAL

33. BUCCAL MUCOSA SKIN MUSCLE ADIPOSE TISSUE MUSCLE Buccinator CHEEK: Germ-layer Origins MUSCLE migrated somitic MESODERM BUCCAL MUCOSA Oral ECTODERM SKIN Surface ECTODERM CONNECTIVE TISSUE Neural crest MESECTODERM GENERAL

34. GENERAL FACIAL STRUCTURES thus depart from body plan MUSCLE migrated somitic MESODERM BUCCAL MUCOSA Oral ECTODERM SKIN Surface ECTODERM CONNECTIVE TISSUE Neural crest MESECTODERM ECTODERM MESODERM ENDODERM SKIN

35. FACIAL & ORAL STRUCTURES More sources Neural crest MESECTODERM also forms cartilage, bone & some periodontal tissues ORAL ECTODERM also forms anterior salivary glands , dental organs & enamel GENERAL

36. Mid-sagittal section CARDIAC BULGE Full-face view 4-w embryo What is going on inside the cranial end of the embryo? E.g., plans for nose & mouth? GENERAL BRAIN HEART I II CORD

37. PHARYNGEAL ARCHES covered by ectoderm & demarcated by PHARYNGEAL GROOVES Mid-sagittal section of 4-w embryo BRAIN HEART ESOPHAGUS MESECTODERM PHARYNGEAL POUCHES lined by endoderm AORTA I II CORD CARDIAC BULGE GENERAL

38. Mid-sagittal section of 1-m embryo OLFACTORY PLACODE off the midline STOMODEUM FRONTONASAL PROMINENCE BRAIN PHARYNGEAL ARCHES covered by ectoderm I II NOSE

39. OLFACTORY PLACODE Lens & Otic similar BRAIN ECTODERM OLFACTORY PLACODE Neural crest MESECTODERM OLFACTORY PLACODE’s rims rise, so creating & deepening the nasal pit & forming two processes NOSE

40. BRAIN WALL NASAL PIT ORAL CAVITY NASOLATERAL PROCESS NASOMEDIAL PROCESS ORONASAL MEMBRANE MANDIBULAR ARCH TONGUE START OF NASAL CAVITY & NOSTRIL (Naris) NOSE

41. ORONASAL MEMBRANE breaks down, creating a passage - primitive choana - between nasal & oral spaces BRAIN WALL ORAL CAVITY NASOMEDIAL PROCESS moves to fuse with its fellow & start primary palate MANDIBULAR ARCH protrudes with the support of Meckel’s cartilage TONGUE NASAL CAVITY- next events Upper nasal lining differentiates into olfactory mucosa NOSE

42. TONGUE Secondary PALATE will grow from maxillary process toward the midline NASAL SEPTUM grows down in midline from frontonasal prominence Nasomedial processes forming tip of nose & intermaxillary segment NASAL CAVITY- more events & slightly later 1 nasal- oral cavity Primary palate growing back NARIS primitive choana NOSE

43. TONGUE Protrusions for NASAL CONCHAE grow in from lateral nasal process Respiratory mucosa diffferentiating NASAL CAVITY- more events & slightly later 2 nasal oral NOSE

44. NASAL CAVITY at 3-m, just off the midline TONGUE LIP BRAIN NASAL CONCHAE Olfactory bulb JAW SECONDARY PALATE NARIS LIP PHARYNX Hence no nasal septum olfactory mucosa NOSE

45. INTERMAXILLARY SEGMENT Sagittal BRAIN PHILTRUM of LIP PRIMARY PALATE LIP 4-INCISOR MAXILLA = INTER-MAXILLARY SEGMENT 1 2 3 PALATE

46. EYE NASAL SEPTUM grows down in midline from frontonasal prominence & nasomedial process? BRAIN LATERAL PALATINE SHELF/PALATAL PROCESS TONGUE MECKEL’S CARTILAGE PALATE FRONTAL SECTION at 6-w

47. PALATE EYE develops NASAL SEPTUM grows down durther BRAIN LATERAL PALATINE SHELVES grow inwards & elevate TONGUE MECKEL’S CARTILAGE degenerates to be replaced by mandibular bone PALATE FRONTAL SECTION at 6-w: next events TONGUE drops below meeting palatine processes LATERAL WALL grows in as conchae

48. PALATE EYE PALATE FRONTAL SECTION at 8-w TOOTH BUD * Site for meeting and fusion of nasal septum & palatal shelves BRAIN TONGUE * NASAL SEPTUM LATERAL PALATINE SHELF MECKEL’S CARTILAGE mandibular bone NASAL CONCHAE Maxillary bone

49. MECHANISMS OF DEVELOPMENT 7 Fate of fused ectoderm II Penetration of dissolving fused ectoderm by mesenchyme E.g., fusion of palatal processes GENERAL

50. PALATE PROXIMITY Epithelial disintegration & conversion Mesenchymal continuity FUSION Epithelial & Mesenchymal differentiation STEPS IN PALATAL-NASAL FUSION

51. PALATE TONGUE X X X X X X Mandibular bone NASAL CONCHAE FACIAL REINFORCEMENT X Skeletal muscle starting Tongue gets larger, develops papillae X X SEPTAL CARTILAGE Maxillary bone TOOTH BUD not seen in every section HARD PALATE VESTIBULAR LAMINA

52. NARIS INTER-MAXILLARY SEGMENT PALATE FROM BELOW GUM LATERAL PALATINE PROCESS/SHELF PRIMARY PALATE/ Median palatine process NASAL SEPTUM (mostly from median nasal processes) UPPER LIP PALATE

53. LATERAL PALATINE PROCESS/SHELF PRIMARY PALATE/ Median palatine process Once the primary palate is fused in place, the lateral shelves meet & fuse zipper-like towards the rear PALATE FROM BELOW Fusion between PALATE

54. PALATE FROM BELOW a little later LATERAL PALATINE PROCESS/SHELF PRIMARY PALATE/ Median palatine process Once the primary palate is fused in place, the lateral shelves meet & fuse zipper-like towards the rear fuses with NASAL SEPTUM partly hidden by palate Incisive foramen PALATE

55. PALATE FROM BELOW 12-w GUM SOFT PALATE UPPER LIP HARD PALATE PALATE

56. PALATE FROM BELOW 12-w SOFT PALATE Uvula last site to fuse UPPER LIP Developing 1 0 Incisors not yet erupted Raphe of HARD PALATE Incisive papilla GUM Frenulum of PALATE

57. PALATAL DEFECTS I: Partial failures to fuse UNILATERAL CLEFT LIP Lateral palatines Maxillary & Nasomedial PALATE CLEFT UVULA/ BIFID UVULA ANTERIOR CLEFT PALATE Incomplete & Unilateral Primary & Lateral palatines

58. PALATAL DEFECTS II: Failures to fuse POSTERIOR CLEFT PALATE Complete COMPLETE UNILATERAL ANTERIOR CLEFT Palate & Lip Primary & Lateral palatines PALATE Can occur independently; can be partial; anterior can be bilateral Maxillary & Nasomedial AND

59. Mid-sagittal section of 1-m embryo ORO/BUCCO-PHARYNGEAL MEMBRANE FRONTONASAL PROMINENCE STOMODEUM BRAIN I II TONGUE PHARYNGEAL ARCHES covered by ectoderm PHARYNGEAL POUCHES lined by endoderm

60. Mid-sagittal section of 1-m embryo Next slides will schematize & simplify floor of Arches I-IV TONGUE BRAIN I II Pouch pattern is more complicated & does not quite match arch pattern PHARYNGEAL ARCHES covered by ectoderm PHARYNGEAL POUCHES lined by endoderm

61. TONGUE Endodermal lining of pharyngeal pouch ARCH I II Pharyngeal groove I III IV Site of Tongue development: inside Endodermal lining of pharyngeal pouch Ectodermal covering Mesenchymal core Arch cut into

62. MECHANISMS OF DEVELOPMENT 2 Differential growth of tissues, e.g., mesenchyme growing more than overlying ectoderm to yield protrusions/ buds ECTODERM MESENCHYME Mesenchyme has grown more & unevenly Surface is greater so that some ectodermal proliferation must have occurred GENERAL

63. Sources of Tongue development I provides growing power to produce bulges/buds Mesenchymal core ARCH I II III IV TUBERCULUM IMPAR Median tongue bud LATERAL LINGUAL SWELLINGS COPULA HYPOBRANCHIAL EMINENCE OCCIPITAL MYOTOMES muscle core TONGUE

64. Sources of Tongue development but not Arch II; & some structures lag & are incorporated ARCH I II III IV ARCH I ARCH III Terminal sulcus TONGUE

65. Sources of Tongue development II ARCH I II III IV LATERAL LINGUAL SWELLINGS HYPOBRANCHIAL EMINENCE OCCIPITAL MYOTOMES muscle core TUBERCULUM IMPAR & COPULA leave no adult mark TONGUE

66. TONGUE TONGUE MALFORMATIONS I ARCH I II III IV LATERAL LINGUAL SWELLINGS Failure of these to fuse properly causes a DEEP MEDIAL SULCUS or at worst a BIFID TONGUE Overgrowth - MACROGLOSSIA Undergrowth - MICROGLOSSIA

67. TONGUE TONGUE MALFORMATIONS II FORAMEN CECUM from whence the thyroglossal duct set out to create the thyroid gland Remnant of duct epithelium forms a LINGUAL CYST Part of duct opens back to foramen - “FISTULA”

68. TONGUE MALFORMATIONS III: Ankyloglossia normal LINGUAL FRENULUM short LINGUAL FRENULUM restricts tongue protrusion Ankyloglossia = Tongue-tied TONGUE

69. Tongue Innervation TONGUE Trigeminal V ARCH I II III IV Facial VII Glossopharyngeal IX OCCIPITAL MYOTOMES muscle core Hypoglossal XII Vagus X CRANIAL NERVE

70. Tongue Innervation TONGUE OCCIPITAL MYOTOMES muscle core Trigeminal V I II III IV Facial VII Glossopharyngeal IX Hypoglossal XII Vagus X Mandibular Trigeminal SENSORY Hypoglossal MOTOR Glossopharyngeal & Facial TASTE Vagus