DEVELOPMENTAL NEUROSCIENCEDifferential regulation of tyrosine hydroxylase expression by sonic hedgehogKwon, II Suna b; Park, Rae Heea; Choi, Jung Mia b; Kim, Seung U.c; Lee, Young Dona b; Suh-Kim, Haeyounga b cAuthor Information aDepartment of Anatomy bNeuroscience Graduate Program and cBrain Disease Research Center, Ajou University, School of Medicine, Suwon, Korea Correspondence and requests for reprints to Haeyoung Suh-Kim, PhD, Department of Anatomy, Ajou University, School of Medicine, Suwon 443-749, South Korea Tel: +82 31 219 5033; fax: +82 31 219 5039; e-mail: email@example.com Sponsorship: This research was supported by the Brain Research Center of the 21st Century Frontier Research Program (Grant No. M103KV010010 04K2201 01010) to H.S.K. and grants from the Brain Disease Research Center at Ajou University to H.S.K. and S.U.K. Received 23 November 2005; accepted 3 February 2006 NeuroReport: May 15th, 2006 - Volume 17 - Issue 7 - p 693-698 doi: 10.1097/01.wnr.0000209043.66482.0b Buy SDC Metrics Abstract Sonic hedgehog functions to induce floor plate in early stages, and spinal motor neurons and midbrain dopaminergic neurons in later stages of development. Here, we investigated the effects of sonic hedgehog on tyrosine hydroxylase expression in three cell lines that correspond to different stages of neural development. Sonic hedgehog increased the tyrosine hydroxylase gene expression in pluripotent P19 cells but repressed it in tyrosine hydroxylase-producing PC12 cells. Promoter analysis in mouse neural stem cells indicated that the N-terminal of sonic hedgehog repressed both the basal and cAMP-dependent protein kinase A-mediated tyrosine hydroxylase activity. These results suggest that the N-terminal of sonic hedgehog increases tyrosine hydroxylase gene expression in cells to acquire dopaminergic phenotypes, but decreases expression in late born neurons by antagonizing the protein kinase A cAMP-responsive element binding protein pathway. © 2006 Lippincott Williams & Wilkins, Inc.