GDA 1-2.txt

• 1st week
• a. Preimplantation: first six days after fertilization
• a.i. no blood supply between mother and fetus
• a.ii. rapid cell division occurs
• a.iii. zygotes  2 cells  4 cells  8 cells  12-16 cells  blastocyst (5 days)  implantation (6 days)

6 days

• 2nd week
• a. developing embryo is a flat sheet of cells/ a disc
• b. bilaminar embryonic disc consists of two layers (upper and lower), which forms embryo
• b.i. epiblast and hypoblast
• c. center region of the bilaminar disc forms primitive streak
• c.i. epiblast cell division forms the primitive streak

• bilaminar
• cells divide and move in through the primitive streak to populate a middle cell layer.

• 3rd week
• a. Trilaminar disc
• a.i. trilaminar – epiblast cells divide and move in through the primitive streak to populate the middle cell layer
• a.i.1. epiblast, migratory cells, and hypoblast
• a.i.2. migratory comes from the epiblast
• a.ii. polarity of trilaminar disc = asymmetry in the disc
• a.ii.1. head is larger due to more rapid cell division compare to tail
• a.ii.2. head is cephalic and tail is caudal
• a.ii.3. oral pharyngeal membrane is the future mouth site
• a.iii. trilaminar disc becomes ectoderm, mesoderm, and endoderm (the three primary germ layers)

• b.i. Notochord
• b.i.1. provides support for the embryo
• b.i.2. induces the overlying ectoderm to specialize and undergo neurulation
• b.i.3. it is made of cartilage from the mesoderm region (region that influence cell behavior in midline)
• b.i.4. helps the convexity of the formation of the neural tube
• b.ii. Process:
• b.ii.1. Ectoderm cells in the midline starts to divide more than the cells that are lateral to them
• b.ii.2. Notochord directs the invagination of ectoderm cells
• b.ii.3. Formation of the neural tube
• **** two parts of the ectoderm (neural fold and neural groove) are involved
• b.iii. Neural tube forms the spinal cord, brain, and vertebral column
• b.iv. Neural tube defects - tube failing to close
• b.iv.1. associated with folic acid deficiency

• c.i. started from cells in ectoderm and has now moved to mesoderm layer when neural tube is formed
• c.ii. resulting tissue = ectomesenchyme
• c.ii.1. named due to origin from neuroectoderm and location in mesoderm layer
• c.ii.2. embryonic connective tissued needed for craniofacial development
• c.iii. behavior similar to cancer cells due to
• c.iii.1. uncontrolled division
• c.iii.2. moving to new locations
• c.iv. Failure of Neural Crest Cell Migration  Treacher-Collins Syndrome (mandibular dysostosis)
• c.iv.1. underdevelopment of mandible (lower jaw)
• c.iv.2. syndrome involves a package of related findings

• Neural crest cells migrate and populate the mesoderm layer
• embryonic connective tissue needed for craniofacial development

• similar to cancer cells, that can metastasize to new locations
• -Neural crest cells are studied because of their significance in embryological development, but also as part of oral cancer research

• d.i. four main layers (ecto, meso, endo, and neural crest cells
• d.ii. Orofacial Structures
• d.ii.1. ectoderm – epidermis, oral mucosa, enamel
• d.ii.2. mesoderm – skeletal muscle
• d.ii.3. endoderm – lining of the gut (pharynx)
• d.ii.4. neural crest – connective tissue proper (supporting tissue), cartilage, bone, dentin, cementum, pulp, periodontal ligament (PDL)
• d.iii. If neural crest cells removed, only enamel appears in the mouth
• d.iii.1. bone does not form well like in Treacher-Collins Syndrome)

• 4th week
• (folding occurs to form 3D shape - before this shape has been 2D)
• a. differential cell division occurs – cells divide more rapidly on one side driving the folding
• b. Process
• b.i. folding occurs along the lateral axis
• b.ii. folding then occurs along the head-tail axis
• b.ii.1. head fold is large - more divisions occur here
• *** brings the tissues into their proper position for further development
• c. A tube-like embryo results
• c.i. ectoderm on the outside
• c.ii. tube of endoderm inside
• c.iii. mesoderm in the middle

Epidermis, Oral Mucosa, Enamel

Skeletal muscle

Lining of the gut (pharynx)

Connective tissue proper, cartilage, bone, dentin, cementum, pulp, PDL (periodontal ligaments)

increase in organization and complexity

increase in size at the cell, tissue, organ, and organism levels

prominence caused by differential growth of the underlying tissue in that region

• 4th to 12th week
• a. Definitions
• a.i. Development – increase in organization and complexity (3 weeks)
• a.ii. Growth – increase in size at the cell, tissue, organ, and organism (3-6 mos)
• a.iii. Process – prominence caused by differential growth of the underlying tissue in that region
• a.iii.1. frontonasal process – forehead and nose region
• a.iii.1.a. enlarged area due to differential growth
• a.iv. Fusions – occurs between processes
• a.iv.1. True Fusion – thru and thru connection (i.e. palate and mandible)
• a.iv.2. Apparent Fuusion - tissues fold in (not separated; origin in one piece)
• a.v. Teratogens – agents that cause developmental defects
• a.v.1. examples: X-rays, drugs, alcohol (causes fetal alcohol syndrome), infectious agents, and nutritional deficiencies

• (vs. apparent)
• two processes come together & completely fuse, eliminating film of tissue where fusion occurred, ex. when palate forms
• Medial Nasal process fusing with maxillary process(becomes philtrum)

• (vs. true fusion)
• tissues fold in (not separated; origin in one piece)
• groove is leveled out & seam erased
• Ex. Medial nasal processes fusing with each other

agents that cause developmental defects.

• b.i.1. Lens placode  eyes
• b.i.2. Site of otic placode  ears
• b.i.3. Frontonasal process  forehead
• b.i.4. Nasal placodes  nostrils
• b.i.5. Stomodeum  mouth
• b.i.6. Near branchial arches  developing heart

• Meckel’s cartilage, trigeminal nerve -> mm of mastication
• mandibular processes which fuse in the midline
• maxillary procceses from from the mandibular arch and grow on either side of stomodeum

Reichart’s cartilage, facial nerve mm of facial expression

the external ear canal meets the eustachian tube at the tympanic membrane

• bars of tissue seen in vertebral development
• b.ii.1. 1st, 2nd, and 3rd play a role in development of face, mouth and tongue
• b.ii.2. Structure
• b.ii.2.a. basic - includes cartilage (derived from neural crest), a nerve, muscle, and blood vessels sounded by mesenchyme
• b.ii.3. 1st or mandibular arch – Meckel’s cartilage, trigeminal nerve (CN V), muscles of mastication
• b.ii.3.a. mandible and maxilla origination
• b.ii.4. 2nd or hyoid arch – Reichart’s cartilage, facial nerve (CN VII), muscles of facial expression
• b.iii. Fate of grooves and pouches
• b.iii.1. between 1st and 2nd arches the external ear canal meets the Eustachian tube at the tympanic membrane
• b.iii.2. groove from the ectodermal side (external auditory meatus) meets with the tube of the endodermal side
• b.iii.2.a. this produces the tympanic membrane and Eustachian tube

keep in mind adult derivative: mandibular process derivative extends superiorly up side of face, interrupting maxillary process derivative along midine is frontonasal process derivative

• b.iv.1. Process
• b.iv.1.a. mandibular processes from the 1st arch fuses at the midline (true fusion)
• b.iv.1.a.i. this includes the bone and soft tissue involved
• b.iv.1.b. bilateral maxillary processes form from the mandibular arch and grow on either side of the stomodeum
• b.iv.1.b.i. maxillary processes don’t fuse with each other but fuse with medial nasal process (abnormal fusion produces cleft lip on the sides of philtrum)
• b.iv.1.b.ii. fusion of the medial nasal processes forms the philtrum
• b.iv.1.c. the frontonasal process is growing along with the enlargement of the underlying brain
• b.iv.1.c.i. the sites of the future nose and eyes
• b.iv.1.c.ii. larger to accommodate the underlying brain
• b.iv.1.d. Nasal placode moves toward the midline to form nostrils

• b.v.1. early development of the nose
• b.v.1.a. lower jaw already produced – mandibular processes fused (true fusion)
• b.v.1.b. medial and lateral nasal processes formed
• b.v.1.b.i. medial nasal processes fuses with each other (apparent fusion)
• b.v.1.b.i.1. forms middle of nose and philtrum
• b.v.1.b.i.2. abonomal fusion  cleft lip in the middle  philtrum fails to fuse
• b.v.1.b.ii. medial nasal process fuse with maxillary process (true fusion)
• b.v.1.b.ii.1. abnormal fusion  cleft lip (could be R or L)
• b.v.1.b.iii. lateral nasal process forms the side of the nose

• b.v.2.a. Maxillary process enlarge and grow
• b.v.2.b. Nasal placodes thickens and appears on the frontnasal process
• b.v.2.c. Nasal placodes invaginates to form oral nasal pits
• b.v.2.d. Rims of nasal pits forms lateral and medial nasal processes
• b.v.2.e. Medial nasal processes migrate toward each other
• b.v.2.f. Mandibular processes fuse and form lower lip
• b.v.2.g. Nasal pits fuse and form nasal sac
• b.v.2.h. Medial nasal processes fuse and form intermaxillary process
• b.v.2.i. Intermaxillary process gives rise to nose bridge, nose septum, and philtrum
• b.v.2.j. Frontal process and medial nasal process grow and form midline nasal septum
• b.v.2.k. Maxillary and Mandibular processes fuse forming check and reducing mouth to its width

• (more complicated  more possible defects)
• Process
• b.vi.1.a. floor of nasal cavity is posterior extension of intermaxillary process /segment  primary palate
• b.vi.1.a.i. from fusion of medial nasal processes
• b.vi.1.b. palatal shelves grow vertically on either side of the developing tongue
• b.vi.1.b.i. shelves are thin medial extensions from maxillary processes
• b.vi.1.c. palatal shelf eleation occurs rapidly bringing the shelves into proximity
• b.vi.1.c.i. tongue moves downward and shelves rotate upwards towards midline growing horizontally
• b.vi.1.d. palatal shelves fuses to each other and nasal septum follows
• b.vi.1.d.i. fuses ventrodorsally with each other, primary palate and inferior nasal septum
• b.vi.1.d.i.1. ventral secondary plate becomes bony hard palate through mesenchymal condensations (endochondral ossification)
• b.vi.1.d.i.2. dorsal secondary plate becomes the soft palate through myogenic mesenchymal condensation
• b.vi.1.d.ii. separates the mouth and nasal cavity

• b.vi.1.d.iii.1. failure of palatal shelves to fuse
• b.vi.1.d.iii.2. incorrect shelf elevation (blocked by tongue)
• b.vi.1.d.iii.3. excessively wide head
• b.vi.1.d.iii.4. ruptures after fusion
• b.vi.1.d.iv. epithelial tissue pouches meeting must be
• removed for seam to be gone – undergoes apoptosis

• b.vi.2.a. Primary palate with four incisor teeth
• b.vi.2.b. Secondary palate formed from fused palatal shelves with canines and posterior teeth
• b.vi.2.b.i. formation of hard and soft palate
• ***secondary palate must fuse with primary palate

• b.vi.3.a. Cleft Uvula
• b.vi.3.b. Posterior Cleft – palatal shelves failed to fused at the back
• b.vi.3.c. Unilateral Cleft Lip and Anterior Cleft Palate – medial nasal and maxillary processes failed to fused along with primary and secondary palate on one side
• b.vi.3.d. Bilateral Cleft Lip and Anterior Cleft Palate – medial nasal process maxillary processes failed to fused along with primary and secondary palate on both sides
• b.vi.3.e. Bilateral Cleft Lip and Anterior and Posterior Cleft Palate - medial nasal process maxillary processes failed to fused along with primary and secondary palate on both sides and secondary palates too
• V. 12th week – elements of orofacial region development are complete
• a. growth is slow during the first trimester when differentiation and morphogenesis are taking plate
• b. rate of growth is only 7 inches long

palatal shelves failed to fused at the back

medial nasal and maxillary processes failed to fused along with primary and secondary palate on one side

medial nasal process maxillary processes failed to fused along with primary and secondary palate on both sides

medial nasal process maxillary processes failed to fused along with primary and secondary palate on both sides and secondary palates too

• a.i. 3. Embryonic folding
• a.ii. 2. Neural tube closure
• a.iii. 1. Formation of the trilaminar disc
• a.iv. 4. Fusion of the mandibular processes
• 3

• b.i. Ectoderm – Dentin (pulp supporting tissue/cementum – from neural crest); Enamel is from ectoderm
• b.ii. Mesoderm – Meckel’s cartilage (from neural crest cells)
• b.iii. Endoderm – lining of the oral cavity (from ectoderm); until the end of pharynx from then on is mesoderm
• b.iv. Neural crest – bone of the mandible
• 4

• c.i. Maxillary and Mandibular
• c.ii. Maxillary and medial nasal
• c.iii. Mandibular and frontonasal
• c.iv. Lateral nasal and maxillary
• c.v. Multifactorial
• 2

• d.i. Maxillary with mandibular
• d.ii. Mandibular with mandibular
• d.iii. Maxillary with median nasal
• d.iv. Mandibular with lateral nasal
• 2

• tightly connected structures
• skin, oral mucosa, glands

• loose and fewer cells (supports cells)
• bone, cartilage, connective tissue proper

• Structure – condyle, ramus, and body
• Connected to the temporal bone via the temporalmandibular joint via the mandibular condyle
• Consists of Meckel’s Cartilage (R and L) (lateral to cartilage is where mandible develops)
• developed from 1st branchial arch (mandibular arch)
• supports/scaffold for mandibular process
• later forms the incus and malleus

• (bone made directly)
• de novo initiation; production of bone matrix, and ossification within the ectomesenchyme
• ectomesenchyme – embryonic connective tissue and are neural crest cells that migrate from ectoderm

cartilage formed and is replaced by bone

• 7 weeks – intramembranous ossification of body of the mandible occurring lateral to Meckel’s Cartilage
• initial site of osteogenesis (mesenchyme) -> chondrocytes
• between incisive br. (medial) and mental br. (lateral)
• both are branches of the alveolar nerve that is associated to Meckel’s Cartilage
• ossification spreads anteriorly and posteriorly to form the bone of the mandible on both sides
• bones doesn’t fuse at the midline
• Meckel’s Cartilage doesn’t contribute directly to the ossification of the mandible
• bone formation of the mandible starts lateral to it
• tissues around the area also forms

• a.i. TMJ - articulation of the mandibular condyle withy the mandibular fossa of the temporal bone
• a.i.1. external auditory canal is near the TMJ articulation
• a.ii. TMJ components via virtual dissection of preauricular approach (opening the tissue at pre auricular canal)
• a.ii.1. mandibular condyle
• a.ii.2. articular surface of the temporal bone
• a.ii.3. capsule
• a.ii.4. articular disc
• a.ii.5. 3 ligaments: temporomandibular, stylomandibular, and sphenomandibular ligaments
• a.ii.6. lateral pterygoid muscle – protrudes jaw/moves mandible
• *** on a typical radiograph, only the condyle and temporal bone are seen, the articular disc cannot be seen

• lubricated by synovial fluid (reduces friction)
• fibrous capsule (dense connective tissue) keeps the fluid in
• contains upper and lower synovial cavities
• prevents dislocation, separation, arthritis

• TMJ articular surfaces are covered with fibrous connective tissue
• different from knee joint, which has hyaline cartilage
• articular surfaces moves and not the connective tissue

• Hinging or Rotation – opens little
• this is what typodonts do – condyle rotates
• Sliding or Translation – opens wide
• condyle moves forward to temporal bone (whole mandible moves forward)
• some can move forward and muscles tightens = LOCK JAW
• must be guided back using thumb on molar and pushing it down
• patients doesn’t usually have pain

• surfaces of condyle are fibrous cartilage (in knee  hyaline cartilage)
• articular disc separates the two cavities in TMJ; knee joint just has one filled with synovial fluid
• TMJ has a hinge, sliding
• two joints can’t operate separately for TMJ; knee joint doesn’t have to work together

• compound joint with upper and lower compartments separated by articular disc
• hinge-sliding fuction
• one joint can’t operate independently
• fibrous articular surfaces on condyle, disc, and temporal bone
• late embryogenesis compared to other synovial joints

• Condylar Cartilage formation
• between 12-14 weeks
• form from endochondrial process
• gcartilage grows and dies, then leaves space behind
• blood vessels/nerves are drawn to these spaces forming ossification center (primary and secondary)
• bones replace these spaces that are left behind
• bone growth is away from the articulating surfaces
• articulation is not affected
• Formation of Joint Spaces between 13-14 weeks through selective cell death
• Meckel’s Cartilage gets smaller during this time

• Meckel’s cartilage is still present in small amount, but mostly mandible has formed;
• on the top, where the condyle will form, is the condylar cartilage
• cartilage is growing superiorly, but can only become so thick;
• as it grows superiorly, cartilage cells at the cartilage-bone juncture die (bc of limitation of thickness) and bone cells fill in > endochondral bone formation

• Intramembranous bone formation begins at 7 weeks (frontal bone
• Body and ramus
• Frontal bone –grows at the margins/periphery because middle is calcified/mineralized
• Endochondral-condyle

• during development size is reduced
• lower vertebrate – it becomes the jaw bone
• humans – it becomes incorporated into parts of the ear (malleus and incus – ear ossicles)

• made of connective tissue
• articulations that allow adjacent bones to grow while maintaining a fibrous junction
• location when 2 bones grow/come together
• sutures gives space when brain grows
• brain becomes inactive when craniofacial growth is complete
• if it prematurely inactivates  craniosyntosis occurs

• suture closes prematurely
• sutures can expand and so brain goes somewhere else  towards the side, front and back
• affects neuronal processes

• head is bigger proportionally to the body and then it gets smaller proportionally as a person ages
• from 9 to 36 weeks, a 425x increase in size of the fetus occurs
• growth – peaks after organs and tissues have been formed