GIL

• Embryo

  The unborn offspring in the process of development, in the period from fertilization until birth
• Odontogenesis

  The process of tooth development
• Embryology

  The study of the development of an embryo and fetus
• Week 1: fertilisation, implantation


  1. Ovum & sperm meet in uterine tube -> zygote -> forms morula (through mitosis & cleavage) -> blastocyst (increase in cell size w/ no change in cell number; consists of 2 types of cells - trophoblast & embryoblast). Implantation on 7th day

  2. Trophoblast: helps embryo to attach to the uterus wall; embryo's contribution to placenta

  3. Embryoblast: becomes the embryo

  
• Week 2: bilaminar embryonic disc


  1. Blastocyst proliferates, forming the bilaminar embryonic disc

  2. Cells receive external induction signals to differentiate into epiblast or hypoblast cell

  3. Epiblast, primary ectoderm & dorsal columnar cells -> amniotic cavity

  4. Hypoblast, primary endoderm & ventral cuboidal cells -> yolk sac

  5. Disc is suspended between these two cavities

  6. Prochordal plate: thickened area where the epiblast & hypoblast meet --> first visual sign of embryonic axis development
• Week 3: trilaminar disc; neurulation & NCC migration; mesoderm differentiation


  1. Cells of the amniotic cavity differentiate & burrow to form the primitive streak

  2. Epiblast cells (soon to be ectoderm) move towards the hypoblast (soon to be endoderm) to form the mesoderm

  3. Neurulation: ectoderm cells -> neural plate -> invaginates inwards to form neural groove & folds -> neural folds undergo fusion to become neural tube -> neural tube later becomes brain & spinal cord

  4. NCC: develop from neuroectoderm -> epithelial-mesenchymal transformation; migrates from the crests of neural folds to join the mesoderm --> mesenchyme --> ectomesenchyme

  5. Mesoderm -> somites
• Week 4: formation of stomadeum, forebrain, tongue


  1. Rostrocaudal axis folding -> primitive stomadeum

  2. Neural tube expansion -> primitive forebrain

  3. Tongue: from local proliferation of mesenchyme in the floor of the mouth (tuberculum impar & lingual swellings at 1st branchial arch, fuse with hypobranchial eminence)

  
• Week 5: olfactory placode & nasal process development


  1. Olfactory placode: localised thickenings within ectoderm of frontal prominence

  2. Nasal process: proliferation from mesenchyme around olfactory placode

  3. Lateral nasal process

  4. Medial nasal process
• Formation of lips


  1. Week 5: formation of lower lip (apparent fusion of Md processes)

  2. Week 7: formation of upper lip

  3. Middle portion (+ philtrum, primary palate, anterior maxilla): medial nasal processes + frontonasal processes

  4. Lateral aspect: ant. aspect of the Mx process + lateral aspect of medial nasal process

  
• Week 6: rudimentary mandible formation

  1. Meckel's cartilage acts as a scaffold for intramembranous ossification; it is then resorbed

  2. Ossification occurs where IAN divides into incisive & mental branch
• Week 7-9: 2º palate formation

  1. Nasal septum grows downwards from frontonasal process

  2. Palatal shelves (from Mx processes): grow downwards -> then ascend -> fusion

  3. By W12: final palate is formed

  
• True fusion

  Breakdown of surface epithelium to allow continuity of the underlying mesenchyme
• Apparent / Faux fusion

  Tissues were originally connected with continuous epithelium, lateral extension eliminates the furrow
• EMT - epithelio-mesenchymal transformation

  Epithelial cells lose cell polarity and cell-cell adhesion > Gaining migratory properties to become mesenchymal stem cells and differentiate into a range of cell types (multipotent)
• Epithelial-mesenchymal interactions

  Programmed communication between epithelial and mesenchymal cells, resulting in further cell differentiation
• Reciprocal induction in amelogenesis


  Interaction between pre-dentine and pre-ameloblasts
• Genetic factors that cause CLP

  • Hox gene mutations: Hox genes act on 3 levels - regulate genes that regulate other genes, regulate effectors genes that form the tissues, structures and organs, regulate cell division & adhesion, apoptosis & cell migration
  • MSX 1 homeobox gene: needed for expression of BMP2 & BMP4 in palatal mesenchyme
  • FGF9: responsible for palatal growth & fusion
• Environmental factors that cause CLP

  • Folic acid: lack of folic acid is associated with neural tube defects
  • Rubella virus
  • Heavy alcohol use during pregnancy
• Suckling


  1. S/P closing nasal passage, lips around bottle or breast, and depression of mandible

  2. Expression of milk from source as tongue presses the source against the H/P

  3. Translocation of milk from oral cavity to GI
• Cleft lip and palate (CLP)

  Consolidation of the nasal and oral cavities and the incompetency of the lips

  
• Effects of CLP

  • Difficulty pronouncing vowels, labial consonants and nasal & oral sounds - due to communication between nasal & oral cavities
  • Hypernasality
  • Increased difficulty when communicating with their caregivers about their needs + difficulty understanding speech from others
• Suckling / swallowing / mastication in those with cleft lip

  • Difficult to achieve a vacuum (negative pressure) due to the consolidation of the nasal and oral cavities and the incompetency of the lips. This makes it difficult to withdraw milk.
  • Swallowing: the food originally aimed to be swallowed to end up in the nasal cavity through nasal regurgitation -> choking / coughing
• Hearing problems in CLP

  • Due to middle ear effusion and related infection
• Dental defects in CLP

  • Agenesis and crowding. This can lead to malocclusion
• Dietary malnutrition in CLP


  • Unable to suckle as well as normal infants
• Sucking mechanism

  1. Levator veli palatini muscle and tensor veli palatini muscle elevate and tense the soft palate to block to nasopharynx: protects airway

  2. Orbicularis oris muscle allows lips to surround bottle or breast

  3. Lateral pterygoid muscle allows depression on mandible
• Swallowing mechanism

  1. Expression of milk suckling from the bottle/nipple occurs next as the tongue presses the bottle or breast against the H/P

  2. Glossopharyngeal muscle elevates the tongue

  3. When liquid reaches palatoglossal arch, S/P remains elevated blocking the nasal cavity, vocal folds close, pharynx elevates and moves anterior by suprahyoid muscle, pharyngeal constrictor muscles move liquid inferior towards the upper oesophageal sphincter
• Oesophageal opening

  1. The upper oesophageal sphincter opens through thyrohyoid contraction, cricopharyngeus relaxation, and distension from the liquid

  2. Once into the oesophagus, liquid travels inferiorly towards stomach by gravity. Upper esophageal sphincter will close while lower esophageal sphincter will open > enter stomach

  
• Molecular causes of CLP

  • Mutations in hox genes & fibroblastic growth factor 9
  • cytokines IL-2 and IFN gamma are highly correlated in promoting mesenchymal cell death
• Cellular causes of CLP

  • NCC: failure to migrate from the crests of neural folds to form mesenchyme
  • due to inappropriate signalling events at a molecular level
  • failure to undergo epithelial mesenchymal transition to give rise to relevant tissues
• Tissue causes of CLP

  • failure of fusion of palatal shelves due to incomplete breakdown of the epithelium
• Organ causes of CLP

  • Failure of tongue depression, preventing the shelves from contacting & fusing together
  • Failure for structures to contact - can be due to failure of mesenchyme proliferation, leading to the shelves not being long enough to make contact
  • Rupture post-fusion
• Odontogenesis


  1. Dental lamina swellings -> Bud stage -> Cap Stage -> Bell stage

  2. Enamel Organ forms Enamel

  3. Dental Papilla forms Dentine & Pulp

  4. Dental Follicle forms Cementum & Periodontal Ligament

  
• Amelogenesis


  Enamel formation
• Dentinogenesis


  Dentine formation

  
• Cementogenesis


  1. Cementum formation

  2. Outer layer of cementoblasts form alveolar bone

  3. Inner layer of cementoblasts form periodontal ligament
• Randomization and its importance
• Lyonisation


  1. inactivation: one of the X chromosomes is randomly and permanently inactivated in cells
• Females less affected than males in sex-linked Amelogenesis Imperfecta
• Amelogenesis Imperfecta


  Hereditary condition affecting enamel formation