Differential regulation of tyrosine hydroxylase expression by sonic hedgehog.
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.
Kwon
Ii Sun
IS
Department of Anatomy bNeuroscience Graduate Program, Ajou University, School of Medicine, Suwon, Korea.
Park
Rae Hee
RH
Choi
Jung Mi
JM
Kim
Seung U
SU
Lee
Young Don
YD
Suh-Kim
Haeyoung
H
D000818:Animals; D015153:Blotting, Western / Q000379:methods; D002454:Cell Differentiation / Q000502:physiology; D002460:Cell Line; D003001:Cloning, Molecular / Q000379:methods; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology*; D053823:Hedgehog Proteins; D051381:Rats; D015398:Signal Transduction / Q000502:physiology; D013234:Stem Cells / Q000502:physiology; D015534:Trans-Activators / Q000737:chemistry / Q000502:physiology*; D014162:Transfection / Q000379:methods; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics / Q000378:metabolism*
D053823:Hedgehog Proteins; D015534:Trans-Activators; D014446:Tyrosine 3-Monooxygenase