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Nat Neurosci 2010 Aug 01;138:944-50. doi: 10.1038/nn.2582.
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cJun integrates calcium activity and tlx3 expression to regulate neurotransmitter specification.

Marek KW , Kurtz LM , Spitzer NC .

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.

PubMed ID: 20581840
PMC ID: PMC2910808
Article link: Nat Neurosci
Grant support: [+]

Species referenced: Xenopus tropicalis
Genes referenced: atf2 jun lbx1 myc slc17a7 tlx3
Morpholinos: tlx3 MO1 tlx3 MO2

Article Images: [+] show captions
References [+] :
Baumgardt, Specification of neuronal identities by feedforward combinatorial coding. 2007, Pubmed