Chapter 21 Outline

The Limb Bud

Hox Gene Specification of Limb Skeleton Identity

• From proximal to distal: Hox genes in the limb
• Hox genes and beyond

Determining What Kind of Limb to Form and Where to Put It

• Specifying the limb fields
• Induction of the early limb bud
• 1. Mesoderm is made permissive by retinoic acid
• 2. Specification by Tbx5 and Islet1
• 3. Induction of epithelia-mesenchymal transitions by Tbx5
• 4. Positive feedback and limb bud formation
• The apical ectodermal ridge generates a second feedback loop

Outgrowth: The Proximal-Distal Axis

• Determining proximal-distal polarity: the role of the AER
• Gradient models of limb patterning

Turing’s model: A mechanism for proximal-distal limb development

• The reaction-diffusion mechanism

Specifying the Anterior-Posterior Axis

• Sonic hedgehog defines a zone of polarizing activity
• Specifying digit identity by Sonic hedgehog
• Sonic hedgehog and FGFs: Yet more feedback loops
• Hox genes are part of the regulatory network specifying digit identity

Generating the Dorsal-Ventral Axis

Cell Death and the Formation of Digits and Joints

• Sculpting the autopod
• Forming the joints

Evolution by Altering Limb Signaling Centers

• Autopod sculpture by our web-footed friends
• Tinkering with the signaling centers: Making whales