Development of the skin & epidermal appendages:

1. periderm - outer layer of flattened ectoderm cells
2. three layers of epidermis form by 3rd month - basal layer is mitotically active
3. dermis of trunk & limbs is somitic; cranial dermis is from neural crest
4. melanocytes - neural crest cells that migrate through dermis into epidermis
5. inductive interactions between epidermis & dermis guide development
6. hair & sebaceous glands - epidermal growths induced by dermis
7. sebaceous glands produce vernix caseosa, anchored by lanugo hairs
8. mammary glands are ectodermal downgrowths occuring along "milk line"
   1. polythelia/polymastia - supernumerary nipple/breast
   2. testicular feminization syndrome - lack of testosterone receptors
9. abnormal skin development
   1. icthyosis - congenital hyperkeratinization
   2. harlequin fetus - epidermal plates separated by deep cracks
   3. angiomas (birthmarks)

Skeletal development - skull:

1. from somitomeres 1-7, occipital somites, & neural crest (cranial vault & face)
2. neurocranium - surrounds brain
   1. membranous neurocranium - cranial vault (intramembranous ossification)
      • fontanelles (6) - anterior, posterior, anterolateral (2), posterolateral (2)
   2. cartilaginous neurocranium (chondrocranium) - cranial base
3. viscerocranium - facial skeleton
   1. membranous viscerocranium - maxilla, mandible, nasal bones
   2. cartilaginous viscerocranium - branchial arch cartilage derivatives
4. abnormal skull development
   1. neural tube defects - anencephaly, microcephaly, encephalocele/meningocele
   2. suture defects - craniosynostosis - scaphocephaly (keel - sagittal), acrocephaly (tower - coronal), plagiocephaly (asymmetrical), metopic suture (fusion by 6 yrs. normally)

Skeletal development - post-cranial axial skeleton:

1. from sclerotome - vertebrae, ribs, & sternum
2. endochondral ossification - hyaline cartilage model calcifies
3. abnormal development of axial skeleton
   1. Klippel-Feil syndrome - brevicollis, short neck
   2. spina bifida occulta, hemivertebrae
   3. accessory ribs, split or fused ribs
   4. pectus excavatum, split sternum/xiphoid, ectopia cordis

Skeletal muscle development:

1. myogenic cells arise from myotomes or cranial somitomeres 1-7
   1. proliferate under influence of FGF and TGF-beta
   2. become myoblasts under influence of increased MyoD expression
   3. myoblasts fuse, forming myotubes
   4. myotubes produce myofibrils (contractile proteins), become muscle fibers
2. myotomal migration
   1. epimere - deep back muscles - innervated by dorsal primary rami
   2. hypomere - all others (including diaphragm) - innervated by ventral rami
   3. abnormal migration - prune belly, exstrophy of bladder

Cardiac & smooth muscle development:

1. cardiac muscle - from splanchnic mesoderm of cardiogenic area
2. smooth muscle - local mesoderm, neural crest (eye)

Limb development:

1. limb buds first appear as ectodermal ridge 26-28 days, upper limb first
   1. FGF-8 and retinoic acid involved in initial stimulus
   2. apical ectodermal ridge (AER) maintains limb growth through FGF, maintains progress zone of mitotically active undifferentiated mesoderm
   3. zone of polarizing activity (ZPA) - located at caudal base of limb bud, through release of sonic hedgehog, it maintains AER and organizes limb in craniocaudal axis
   4. dorsoventral axis is determined by Wnt-7a expression in dorsal ectoderm and En-1 in ventral ectoderm
   5. proximodistal axis determined by Hox expression
2. breakdown of AER in interdigital spaces causes cell death
3. condensation of limb mesenchyme begins endochondral bone formation
4. limb vasculature
   1. axial artery in limb bud core, remodels throughout development
   2. marginal sinus lies beneath AER - cephalic & basilic in upper limb, great & small saphenous in lower limb
5. myotome & dermatome migrations into limb
   1. establishes proximodistal motor innervation pattern
   2. establishes ventral axial line in dermatome sensory innervation
6. limb malformations
   1. amelia - absence
   2. meromelia - reduction/absence of part of limb
      • phocomelia - reduction/absence of arm/thigh
      • hemimelia - reduction/absence of forearm/leg
   3. hand/foot defects
      • syndactyly - fused digits
      • adactyly - no digits
      • ectrodactyly - loss of digits
      • brachydactyly - shortening of digits
      • polydactyly - extra digits
      • club foot (talipes equinovarus) - some caused by oligohydramnios
      • amniotic band amputations
   4. achondroplasia - congenital dwarfism resulting from improper development of cartilage at the ends of the long bones

When you feel ready for some practice questions, have at it.