The homeodomain protein is encoded by a 180 base pair homeobox within the homeotic gene. The limb develops as a cooperative morphogenetic field where the chemicals involved in establishing the three different axes interact cooperatively. Initial positioning of the limb fields Hox gene expression in the anterior to posterior axis of the trunk lateral plate mesoderm determines position of forelimb and hindlimb. The most anterior expression of the Hoxc-6 gene locates the forelimb. Lateral plate mesoderm near the limb field induces some myoblasts from the somite to enter the limb bud.
Retinoic acid is also necessary for initiation of limb bud outgrowth.
The AER is present at the border of the dorsal and ventral surfaces of the limb bud. Roles of AER Maintaining mitotic activity in the underlying mesoderm Maintaining expression of molecules that form the anterior-posterior axis of thr limb. Interacting with proteins involved in specifying all axes of limb differentiation. Other surface ectoderm cannot. Experiments with the AER show that the mesenchyme induces and sustains the AER and determines the type of limb that develops.