N-terminal fatty-acylation of sonic hedgehog enhances the induction of rodent ventral forebrain neurons

The adult basal ganglia arise from the medial and lateral ganglionic eminen ces, morphologically distinct structures found in the embryonic telencephal on. We have previously shown that temporal changes in sonic hedgehog (Shh) responsiveness determine the sequential induction of embryonic neurons that populate the medial and lateral ganglionic eminences. In this report, we s how that Shh-mediated differentiation of neurons that populate the lateral ganglionic eminence express different combinations of the homeobox-containi ng transcription factors Dir, Mash1 and Islet 1/2, Furthermore, we show tha t N-terminal fatty-acylation of Shh significantly enhances its ability to i nduce the differentiation of rat Ell telencephalic neurons expressing Dir, Islet 1/2 or Mash1. Recent evidence indicates that in utero injection of th e E9.5 mouse forebrain with retroviruses encoding wild-type Shh induces the ectopic expression of D1x2 and severe deformities in the brain, In this re port, we show that Shh containing a mutation at the site of acylation preve nts either of these phenotypes, These results suggest that N-terminal fatty -acylation of Shh may play an important role in Shh-dependent signaling dur ing rodent ventral forebrain formation.