Craniofacial Development

  1. Developmental Craniofacial Biology
    1. Molecular regulation of craniofacial morphogenesis
      1. Facial rhombomeres, HOX and OTX2 genes
      2. Patterns of neural crest formation, migration, fates.
    2. Abnormal neural crest development (neurocristopathies), e.g., Treacher Collins syndrome (mandibulofacial dysostosis), Pierre Robin sequence, DiGeorge sequence, Hemifacial Microsomia.
    3. Molecular regulation of skeletal morphogenesis, e.g., Fibroblast growth factors (FGFs) and receptors (FGFRs).
      1. Fibroblast Growth Factor (FGF) gene
      2. Fibroblast Growth Factor Receptor (FGFR) gene
    4. Molecular regulation of eye development, e.g., PAX6, PAX2, BMP7 genes, and sonic hedgehog (shh).
      1. PAX6 gene
      2. PAX2 gene
      3. Sonic hedgehog (shh)
    5. Molecular regulation of palate formation, e.g. Epidermal growth factor (EGF), transforming growth factor-a (TGF? ).
    6. Genes and tissue interactions in tooth development.
    7. "Time table"
      1. Chronology in craniofacial embryology
      2. Critical periods of peak morphogenesis
  2. Craniofacial Embryology
    1. Development of skull
      1. Neurocranium: membranous (desmocranium) and cartilaginous (chondrocranium).
      2. Viscerocranium, e.g. maxilla, palate, mandible.
      3. Morphogenesis of sutures and synchondroses.
    2. Development of the face, eye, nose, lip, palate, tongue, ear
      1. Facial prominences (5).
      2. Roles of olfactory, optic and otic placodes.
      3. Primary and secondary palates.
      4. Pharyngeal arch contributions to tongue formation.
      5. Morphogenesis of the ear - internal, middle, and external ears.
      6. Morphogenesis of the eye
        1. Optic cup and lens
        2. Retina, lens, iris and ciliary body
        3. Choroid, sclera and cornea
        4. Optic nerve
      7. Organization and development of orofacial and tongue muscles.
      8. Morphogenesis of velopharyngeal muscles.
    3. Pharyngeal arches and pouches
      1. Organization of arches and pouches.
      2. Component tissues of arches and pouches.
      3. Structures developing from arches and pouches.
      4. Malformations related to abnormal pharyngeal arch and pouch formation, e.g., branchial fistulae and cysts.
    4. Development of teeth
      1. Stages in typical tooth morphogenesis.
      2. Tissue interactions in tooth development.
      3. Development and plan of primary, mixed, and permanent teeth.
  3. Basic definitions in craniofacial biology
    1. Anomaly (Major): Condition often defined as malformations (or defects) that create significant medical problems and require surgical and medical management.
    2. Anomaly (Minor): Condition often described as morphologic features that vary from those that are most commonly seen in the normal population but, in and of themselves, are not associated with increased morbidity.
    3. Association: A group of anomalies that occur more frequently together than would be expected by chance alone but do not have a predictable pattern or unified etiology.
    4. Critical Periods: Intrauterine (chiefly embryonic) periods of peak organogenesis during which time the embryo is at high risk for teratogen exposure.
    5. Disruptions: A condition where a fetal structure is growing normally and then growth is arrested by a factor(s) that disrupts the normal development process.
    6. Deformation: A condition (often temporary) caused by an abnormal external force on the fetus during in utero development that results in abnormal form and growth of the fetal structure or region.
    7. Dysplasia: Anomalous development related to an underlying tissue disturbance where the cellular architecture or growth of a tissue is not normally maintained throughout development.
    8. Ectoderm: Outermost of the 3 primary layers that forms the nervous system and outer skin (epidermis).
    9. Endoderm: Innermost of the 3 primary layers that forms the lining of the gut.
    10. Etiology: Underlying factors and causes for congenital anomalies or birth defects. Note that the same apparent conditions may have different etiologies in different individuals.
    11. Facial Prominences: These are the five major building-block structures (frontonasal [1], maxillary [2], and mandibular [3]) that play important roles in the formation of the embryonic head and face.
    12. Fibroblast Growth Factor (FGF): A family of signaling key roles in embryogenesis, including that of the limbs, skeleton, and head and face.
    13. Fibroblast Growth Factor Receptor (FGFR): Protein receptor sites located on cell membranes which bind with specific signaling molecules (e.g. Shh, FGF) that transmit molecular signals to the cell nucleus and the specific development of the cell(s).
    14. Field Defects: Term often used to describe related malformations in a particular region and sometimes used interchangeably with the term "sequence".
    15. Genotype: This is the fundamental genetic constitution or composition of an individual.
    16. HOX genes: A set of homeobox genes with identified DNA sequences controlling those that play important roles in morphogenesis of the body, in general, and in specific structures of the head and face.
    17. Malformation: Malformation signifies that fetal development and growth did not progress normally due to underlying genetic, epigenetic, or environmental factors that altered development of a specific structure or structures.
    18. Mesoderm: Middle layer of the 3 primary layers that forms the dermis, bone, cartilage, blood vessels and connective tissue.
    19. Neural Crest: Layer of cells superior to the developing neural tube that migrate to become part of nearly all major structures and organ systems in the body.
    20. OTX gene: A homeobox containing gene that plays an important role along with HOX genes in the embryogenesis of the brain and the morphogenesis of the first pharyngeal arch and its derivatives, especially the craniofacial regions.
    21. Pathogenesis: The cellular basis of abnormal development associated with known or hypothesized etiologies.
    22. Pharyngeal Arches: Paired arches in embryonic neck region separated by pharyngeal grooves which play important roles in development of the head and neck.
    23. Pharyngeal Grooves: Deep depressions between pharyngeal arches in embryonic neck region. The first groove persists and forms the external acoustic meatus.
    24. Pharyngeal Pouches: Outpocketings from the embryonic pharynx wall that play important roles in development of structures, such as the tympanic membrane, tonsils, thymus and parathyroid glands.
    25. Phenotype: Phenotype is the observed result of the interaction of the genotype with environmental factors, i.e. the observable expressions of a particular gene or genes.
    26. PAX gene: The PAX gene family (e.g. PAX2, PAX6) is an important group of genes that play key roles in the morphogenesis of such structures as the ear, eye, and nose.
    27. Rhombomeres: Blocks of tissue located lateral to the embryonic hindbrain (rhombencephalon), which provide for fundamental organization of hindbrain and eventually play key roles in facial development.
    28. Sequence: A group of related anomalies that generally stem from a single initial major anomaly that alters the development of other surrounding or related tissues and structures.
    29. Sonic Hedgehog (shh): A protein "signaling" molecule that plays the most important role in shaping the entire embryo, and in specific structures of the head and face, including teeth.
    30. Syndrome: A condition generally recognized and defined as a well characterized constellation of major and minor anomalies that occur together in a predictable fashion presumably due to a single underlying etiology (e.g. genes, chromosomes, teratogens).

Core Curriculum for Cleft Palate and Other Craniofacial Anomalies