cJun integrates calcium activity and tlx3 expression to regulate neurotransmitter specification.

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.

journal_name

Nat Neurosci

journal_title

Nature neuroscience

authors

Marek KW,Kurtz LM,Spitzer NC

doi

10.1038/nn.2582

subject

Has Abstract

pub_date

2010-08-01 00:00:00

pages

944-50

issue

8

eissn

1097-6256

issn

1546-1726

pii

nn.2582

journal_volume

13

pub_type

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