Sonic hedgehog promotes proliferation and tyrosine hydroxylase induction of postnatal sympathetic cells in vitro

Abstract

The role of Sonic hedgehog (shh) in neural crest development was initially suggested by its involvement in patterning of the neural tube. While largely implicated in cell fate determination during development, its recently discovered role in the development of neurons postnatally prompted the possibility that neural crest derivatives of the sympathoadrenal lineage may respond to Shh postnatally. In the present study, we show that Shh promotes proliferation of postnatal sympathetic cells in culture. While it has been previously found to induce tyrosine hydroxylase (TH) production in the developing midbrain, we also demonstrated that Shh is capable of promoting TH induction of mature sympathetic neurons in vitro. This duality in Shh can be inhibited by activation of protein kinase A. These findings suggest that cell response to Shh is conserved in sympathetic ganglia derived from the neural crest, and further supports the notion that Shh can function postnatally in a dose-dependent manner to mediate neuronal cell fate.