Page "Bistability" Paragraph 9

A prime example of bistability in biological systems is that of Sonic hedgehog ( Shh ), a secreted signaling molecule, which plays a critical role in development.

Shh functions in diverse processes in development, including patterning limb bud tissue differentiation.

The Shh signaling network behaves as a bistable switch, allowing the cell to abruptly switch states at precise Shh concentrations.

gli1 and gli2 transcription is activated by Shh, and their gene products act as transcriptional activators for their own expression and for targets downstream of Shh signaling.

Simultaneously, the Shh signaling network is controlled by a negative feedback loop wherein the Gli transcription factors activate the enhanced transcription of a repressor ( Ptc ).

This signaling network illustrates the simultaneous positive and negative feedback loops whose exquisite sensitivity helps create a bistable switch.