Patterning along the limb bud requires signals from many sources.
Specifically, proteins called transcription factors (TF) help control the rate at which a gene is transcribed.
The limb bud expresses a TF called ALX4 at the anterior part of the mesoderm, with the TF HOXB8 being expressed at the posterior portion.
The Alx4 region, the medial region, and the Hox8 expressing area meet at a proximal area where the AER develops.
The ZPA forms where the Hox8 region joins the AER.

These regions are dependent on signaling in order for the appropriate induction events to occur.
 The AER expresses FGF8    which induces Shh expression in the posterior mesoderm.
 Shh then stimulates FGF4 to be expressed in the posterior part of the AER.
After these events, there is a co-dependence between FGF-4 and Shh for their subsequent expression and maintenance.
Additionally, Wnt7a is expressed in the dorsal ectoderm, is needed to maintain the FGF and Shh signaling.
Patterning along the limb bud requires signals from many sources. Specifically, proteins called transcription factors (TF) help control the rate at which a gene is transcribed. The limb bud expresses a TF called ALX4 at the anterior part of the mesoderm, with the TF HOXB8 being expressed at the posterior portion. The Alx4 region, the medial region, and the Hox8 expressing area meet at a proximal area where the AER develops. The ZPA forms where the Hox8 region joins the AER.
These regions are dependent on signaling in order for the appropriate induction events to occur.  The AER expresses FGF8    which induces Shh expression in the posterior mesoderm.  Shh then stimulates FGF4 to be expressed in the posterior part of the AER. After these events, there is a co-dependence between FGF-4 and Shh for their subsequent expression and maintenance. Additionally, Wnt7a is expressed in the dorsal ectoderm, is needed to maintain the FGF and Shh signaling.
Zone of polarizing activity