Upper Limb Development

Alphonsus Chong Department of Hand and Reconstructive Microsurgery National University Hospital Why bother?

 Most congenital limb anomalies are due to:  Disorders of embryogenesis or  Problems during fetal development Some terminology

 Embryogenesis  0-8 weeks – new organ systems appear  Fetal period  Appearance of primary ossification center in humerus  Differentiation, maturation and enlargement of existing organs Limb Development

 Limb Patterning  Tissue Differentiation  Why is it an arm and not  Skeletal a leg?  Joint  Vascular  Nerve  Muscle and Tendon Positional Information and Axes of the upper limb Limb Bud in E3 Chick Embryo

 Limb bud (lateral plate)  Loose mesenchymal cells from lateral plate mesoderm  Ectodermal epithelial cells  Migrating cells  Somites --> Muscle  Nerves  Vasculature Limb Bud Development

 Limb bud  Ectoderm and mesenchyme  Not fully differentiated yet but all ingredients there  If transplanted  ectopic limb

Limb Bud

 Regions  AER  Progress zone  Zone of polarizing activity AER – Proximal to Distal formation Zone of Polarizing Actvity – AP development Morphogen Gradient Model

Dorsal / ventral patterning less well understood Separation of Digits

 Apoptosis (Programmed cell death) of interdigital mesenchyme  BMPs important  Starts post-axial to pre-axial Mesoderm specifies amount of apoptosis How does this relate to pathogensis?

 Picture from Greene Learning Points

 UE development occurs early in embryogenesis – most risk of development congenital anomalies  Pattern of limb development follows a body plan  Digit formation is by apoptosis Thank You

Further Reading Principles of Development 3rd Ed by Lewis Wolpert. Oxford University Press Growing Hand. Amit Gupta and Louisville Group