XIII. What are the components of embryological development?
A. Gametogenesis, fertilization, Mitosis vs Meiosis
1. Rates of mutation, chromosome rearrangements
2. Chromosomal aberrations (numerical, structural, mosaic) – See IIC
Disease Ex: T21, T18, T13, 45X, 47XXY, 4p-, 5p-, 22q11 del, 7q11 del
B. Embryotic cell cycle and regulation
1. Initial cell divisions
2. Blastocyst and implantation
3. Gastrulation and cell differentiation
Germ layers – ectoderm, mesoderm, endoderm
C. Tissue & organ development
1. Placentation
2. Body cavity development
3. Cardiac development, heart migration, and septation
Disease Ex: Holt-Oram, Kartagener, 22q11 del, 7q11 del
4. GI tract development, rotations, mesentery alignment (with accessory organ budding)
Disease Ex: omphalocele, gastroschisis, Beckwith-Weidemann, Alagille
5. Lung formation and branching morphogenesis
Disease Ex: Potter sequence
6. Skeletal development
Disease Ex: Achondroplaisa, osteogenesis imperfecta
7. Limb bud development and limb rotation
Disease Ex: Holt-Oram, split hand/split foot, thalidomide, amniotic bands
8. UG development and relationship with hindgut
Disease Ex: polycystic kidneys, OEIS complex
9. Gender development
Disease Ex: androgen insensitivity, Smith-Lemli-Opitz, congenital adrenal hyperplasia, 5 alpha reductase
10. Pharyngeal/Branchial arch contributions
Disease Ex: 22q11 del, brancho-oto-renal, Goldenhar, Treacher-Collins
11. Head and face development
Disease Ex: types of clefts (lip, palate, Tessier), Robin sequence, Stickler, T13, vanderWoude, folate
12. Eye development
Disease Ex: micro/anophthalmia, cataracts, coloboma, CHARGE, Alagille, TORCH
13. Ear development
Disease Ex: connexin 26, TORCH / teratogens, Pendred, CHARGE
14. Brain development
Disease Ex: neuronal migration, lissencephaly, Miller-Dieker / LIS1, holoprosencephaly, T13 / sonic hedgehog, anencephaly, hydranencephaly, porencephaly, schizencephaly, hydrocephalus, TORCH / teratogens
15. Neural crest cell migration
Disease Ex: Hirschprung, Waardenburg, neural tube defects, folate
16. Stem cells, bone marrow
Disease Ex: Fanconi anemia, Bloom, severe combined immunodeficiency
D. Dysregulation – genetic vs environmental
1. Normal development vs aberrant development (spontaneous abortion)
2. Birth defect classification: deformation, disruption, dysplasia, malformation (minor, major), syndrome, sequence, association
3. Pattern recognition:
Associations:
Disease Ex: VACTERL
Sequences:
Disease Ex: Pierre-Robin, Potter
Teratogens
Disease Ex:
Drugs (alcohol, tobacco, cocaine, other illicit drugs)
Medications (antiepileptics, folate antagonists, lithium, thalidomide, warfarin, tetracylines, amnioglycosides, alkylating agents, DES, ACE inhibitors)
Environmental (TORCH, X-rays)
Dietary (iodide, folate, vitamin A),
Maternal conditions (diabetes, PKU, epilepsy)
Chromosomal
Disease Ex: T21, T18, T13, 45X, 47XXY, 4p-, 5p-, 22q11 del, 7q11 del
Single gene defects
Disease Ex: Achondroplasia, Apert, Cornelia deLange, Holt-Oram, Treacher-Collins,
Embryonic patterning genes
Disease Ex: sonic hedgehog, T-box, Wnt, SRY
4. Maternal message vs new transcription
Maternal RNA