Title | cJun integrates calcium activity and tlx3 expression to regulate neurotransmitter specification. |
Publication Type | Journal Article |
Year of Publication | 2010 |
Authors | Marek KW, Kurtz LM, Spitzer NC |
Journal | Nat Neurosci |
Volume | 13 |
Issue | 8 |
Pagination | 944-50 |
Date Published | 2010 Aug |
ISSN | 1546-1726 |
Keywords | Animals, Base Sequence, Calcium, Calcium Signaling, Electrophoretic Mobility Shift Assay, Gene Expression, Gene Expression Regulation, Developmental, Homeodomain Proteins, Immunohistochemistry, In Situ Hybridization, Molecular Sequence Data, Neurogenesis, Neurons, Neurotransmitter Agents, Promoter Regions, Genetic, Proto-Oncogene Proteins c-jun, Response Elements, Reverse Transcriptase Polymerase Chain Reaction, Xenopus, Xenopus Proteins |
Abstract | Neuronal differentiation is accomplished through cascades of intrinsic genetic factors initiated in neuronal progenitors by external gradients of morphogens. Activity has been thought to be important only late in development, but recent evidence suggests that activity also regulates early neuronal differentiation. Activity in post-mitotic neurons before synapse formation can regulate phenotypic specification, including neurotransmitter choice, but the mechanisms are not clear. We identified a mechanism that links endogenous calcium spike activity with an intrinsic genetic pathway to specify neurotransmitter choice in neurons in the dorsal embryonic spinal cord of Xenopus tropicalis. Early activity modulated transcription of the GABAergic/glutamatergic selection gene tlx3 through a variant cAMP response element (CRE) in its promoter. The cJun transcription factor bound to this CRE site, modulated transcription and regulated neurotransmitter phenotype via its transactivation domain. Calcium signaled through cJun N-terminal phosphorylation, which integrated activity-dependent and intrinsic neurotransmitter specification. This mechanism provides a basis for early activity to regulate genetic pathways at critical decision points, switching the phenotype of developing neurons. |
DOI | 10.1038/nn.2582 |
Alternate Journal | Nat. Neurosci. |
PubMed ID | 20581840 |
PubMed Central ID | PMC2910808 |
Grant List | MH 074702 / MH / NIMH NIH HHS / United States R01 MH074702 / MH / NIMH NIH HHS / United States R01 MH074702-02 / MH / NIMH NIH HHS / United States R01 MH074702-03 / MH / NIMH NIH HHS / United States R01 MH074702-04 / MH / NIMH NIH HHS / United States R01 MH074702-05 / MH / NIMH NIH HHS / United States R01 NS015918 / NS / NINDS NIH HHS / United States R01 NS057690 / NS / NINDS NIH HHS / United States T32 AG00216 / AG / NIA NIH HHS / United States |
cJun integrates calcium activity and tlx3 expression to regulate neurotransmitter specification.
Category:
Spitzer Laboratory