A somitic contribution to the apical ectodermal ridge is essential for fin formation

Area of Science:

• Developmental biology
• Evolutionary developmental biology
• Comparative anatomy

Background:

• The transition from fins to limbs is a critical evolutionary adaptation for terrestrial life.
• Existing models of this transition focus on the apical ectodermal ridge (AER) and its signaling molecules during appendage outgrowth.
• The AER in fins rapidly forms an apical fold, ceasing signals that promote skeletal precursor proliferation, unlike in limbs.

Purpose of the Study:

• To investigate the developmental mechanisms controlling apical fold induction, a poorly understood aspect of limb evolution.
• To test the hypothesis that a heterochronic shift in the AER-to-apical-fold transition is crucial for limb evolution.
• To identify the cellular and molecular players involved in regulating the fin-to-limb developmental shift.

Main Methods:

• Utilized zebrafish as a model organism to study appendage development.
• Identified and characterized a novel somite-derived cell lineage invading the AER.
• Performed cell ablation experiments to assess the role of these cells in apical fold formation and AER activity.
• Examined the evolutionary presence of these cells across gnathostome species.

Main Results:

• Demonstrated that invasion by a specific somite-derived cell lineage into the AER regulates apical fold induction in zebrafish.
• Ablation of these cells prevented apical fold formation, prolonged AER activity, and increased fin bud mesenchyme.
• Showed that these apical-fold inducing cells are progressively lost during gnathostome evolution.
• Found an absence of these cells in tetrapod limbs, suggesting their loss is linked to limb development.

Conclusions:

• A novel somite-derived cell lineage acts as a timing mechanism for apical fold formation, potentially explaining Thorogood's clock model of fin-to-limb transition.
• The evolutionary loss of these apical-fold inducing cells appears to be a prerequisite for the development of tetrapod limb structures.
• This finding provides a new developmental perspective on a major evolutionary transition in vertebrate history.