• Somatic layer of lateral plate/ splanic mesoderm
• Ectoderm

• Epidermis and derivatives (hairs, nails, sweat, & sebaceous glands)

• Dermis
• Connective tissue
• Tendons
• Cartilage
• Bone
• Muscle

paraxial mesoderm

myotome of somites

• Posterior:Anterior
• Dorsal:Ventral
• Proximal:Distal

• Proximodistal: Limb outgrowth
• Anteroposterior: Digit specification (thunb to ring finger)
• Dorsoventral: AER position, Muscle pattern

• Induced by underlying mesenchyme.
• Secretes FGF-8 & FGF-4 into underlying mesenchyme (progress zone)
• Maintains progress zone by causing the cells close to the ridge to remain undifferentiated and rapidly proliferating.
• The cells further from the AER begin to differentiate into cartilage and muscle in a proximodistal direction.
• Required for limb develpoment.

• Induced by AER
• Secretes  FGF-10 in to AER
• Rapid cell division occurs here
• No differentiation
• Required for limb growth.

• genes that code for the growth of different parts of the limb.
• nested 5' to 3'
• The order that they are expressed are the exact same order that they are in the DNA
• Proximodistal and Anteroposterior
• induced by Shh and FGF-4

• mice lacked radius and ulna
• Indicates genetic speciicity of proximodistal pattern.
• Hoxa-11 and Hoxd-11 were both knocked out. If only one were knocked out there would be less of an issue because one can substitute for another.

• Involved in Digit Specification 
• Located on the posterior border of the limb.
• Encodes posterior positional information.
• If grafted to anterior limb border it will induce a mirror image of the other side.

• Mimics ZPA and stimulates the production of Shh in the anterior part of the bud (if grafted there) resulting in a mirror image limb.
• If too much is used it will kill the limb.
• Also stilumates Hox

• Involved in Digit Specification 
• Normal product of ZPA region
• enduces AER to secrete FGF-4
• Intergrates proximodistal with anteroposterior patterning.
• Induces Hoxd expression.
• Can be induced by RA implants
• Skeletal duplication induced by Shh implants
• Anteroposterior

• Restricted to Dorsal Ectoderm (round side of bud)
• Induces Lmx1 in dorsal mesoderm
• Wnt7a knockouts fail to form an AER
• Dorsoventral

• Restricted to Ventral Ectoderm
• Inhibits r-fng in ventral ectoderm expressing Wnt7a.
• Dorsoventral

• Proximodistal
• secreted by entire AER
• maintains proliferation and inhibits differentiation in progress zone.
• maintained by FGF-10

• Proximodistal
• secreted by posterior AER
• maintains proliferation and inhibits differentiation in progress zone.
• Induced by Shh

• Proximodistal
• secreted by the progress zone
• maintains AER structure and function.

5 weeks: Limbs have formed finlike appendages and point laterally and caudaily.

6 weeks: Limbs bend anteriorly so elbows and knees point laterally. Palms and soles face trunk.

7 weeks: Upper and lower limbs twist 90^o in opposite directions so that elbows point caudaily and knees cranially.

8 weeks: Lower limbs twist more

This explains why there a "barber pole" twisting of the cutaneous innervation of the limbs.