Calcium activation of the LMO4 transcription complex and its role in the patterning of thalamocortical connections

Amir H. Kashani, Zilong Qiu, Linda Jurata, Soo-Kyung Lee, Samuel Pfaff, Sandra Goebbels, Klaus Armin Nave, Anirvan Ghosh

Research output: Contribution to journalArticle

55 Citations (Scopus)

Abstract

Lasting changes in neuronal connectivity require calcium-dependent gene expression. Here we report the identification of LIM domain-only 4 (LMO4) as a mediator of calcium-dependent transcription in cortical neurons. Calcium influx via voltage-sensitive calcium channels and NMDA receptors contributes to synaptically induced LMO4-mediated transactivation. LMO4-mediated transcription is dependent on signaling via calcium/calmodulin-dependent protein (CaM) kinase IV and microtubule-associated protein (MAP) kinase downstream of synaptic stimulation. Coimmunoprecipitation experiments indicate that LMO4 can form a complex with cAMP response element-binding protein (CREB) and can interact with cofactor of LIM homeodomain protein 1 (CLIM1) and CLIM2. To evaluate the role of LMO4 in vivo, we examined the consequences of conditional loss of lmo4 in the forebrain, using the Cre-Lox gene-targeting strategy. The organization of the barrel field in somatosensory cortex is disrupted in mice in which lmo4 is deleted conditionally in the cortex. Specifically, in contrast to controls, thalamocortical afferents in conditional lmo4 null mice fail to segregate into distinct barrel-specific domains. These observations identify LMO4 as a calcium-dependent transactivator that plays a key role in patterning thalamocortical connections during development.

Original languageEnglish (US)
Pages (from-to)8398-8408
Number of pages11
JournalJournal of Neuroscience
Volume26
Issue number32
DOIs
StatePublished - Aug 9 2006
Externally publishedYes

Fingerprint

Calcium-Calmodulin-Dependent Protein Kinase Type 4
Calcium
LIM-Homeodomain Proteins
Calcium-Sensing Receptors
Cyclic AMP Response Element-Binding Protein
Somatosensory Cortex
Microtubule-Associated Proteins
Trans-Activators
Gene Targeting
Calcium Channels
Prosencephalon
N-Methyl-D-Aspartate Receptors
Protein Kinases
Transcriptional Activation
Gene Expression
Neurons

Keywords

  • Barrel cortex
  • Calcium
  • Cortex
  • Development
  • LMO4
  • Transcription

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Calcium activation of the LMO4 transcription complex and its role in the patterning of thalamocortical connections. / Kashani, Amir H.; Qiu, Zilong; Jurata, Linda; Lee, Soo-Kyung; Pfaff, Samuel; Goebbels, Sandra; Nave, Klaus Armin; Ghosh, Anirvan.

In: Journal of Neuroscience, Vol. 26, No. 32, 09.08.2006, p. 8398-8408.

Research output: Contribution to journalArticle

Kashani, Amir H. ; Qiu, Zilong ; Jurata, Linda ; Lee, Soo-Kyung ; Pfaff, Samuel ; Goebbels, Sandra ; Nave, Klaus Armin ; Ghosh, Anirvan. / Calcium activation of the LMO4 transcription complex and its role in the patterning of thalamocortical connections. In: Journal of Neuroscience. 2006 ; Vol. 26, No. 32. pp. 8398-8408.
@article{c1c3540b8cb747d3bca2d4aa6b729bc8,
title = "Calcium activation of the LMO4 transcription complex and its role in the patterning of thalamocortical connections",
abstract = "Lasting changes in neuronal connectivity require calcium-dependent gene expression. Here we report the identification of LIM domain-only 4 (LMO4) as a mediator of calcium-dependent transcription in cortical neurons. Calcium influx via voltage-sensitive calcium channels and NMDA receptors contributes to synaptically induced LMO4-mediated transactivation. LMO4-mediated transcription is dependent on signaling via calcium/calmodulin-dependent protein (CaM) kinase IV and microtubule-associated protein (MAP) kinase downstream of synaptic stimulation. Coimmunoprecipitation experiments indicate that LMO4 can form a complex with cAMP response element-binding protein (CREB) and can interact with cofactor of LIM homeodomain protein 1 (CLIM1) and CLIM2. To evaluate the role of LMO4 in vivo, we examined the consequences of conditional loss of lmo4 in the forebrain, using the Cre-Lox gene-targeting strategy. The organization of the barrel field in somatosensory cortex is disrupted in mice in which lmo4 is deleted conditionally in the cortex. Specifically, in contrast to controls, thalamocortical afferents in conditional lmo4 null mice fail to segregate into distinct barrel-specific domains. These observations identify LMO4 as a calcium-dependent transactivator that plays a key role in patterning thalamocortical connections during development.",
keywords = "Barrel cortex, Calcium, Cortex, Development, LMO4, Transcription",
author = "Kashani, {Amir H.} and Zilong Qiu and Linda Jurata and Soo-Kyung Lee and Samuel Pfaff and Sandra Goebbels and Nave, {Klaus Armin} and Anirvan Ghosh",
year = "2006",
month = "8",
day = "9",
doi = "10.1523/JNEUROSCI.0618-06.2006",
language = "English (US)",
volume = "26",
pages = "8398--8408",
journal = "Journal of Neuroscience",
issn = "0270-6474",
publisher = "Society for Neuroscience",
number = "32",

}

TY - JOUR

T1 - Calcium activation of the LMO4 transcription complex and its role in the patterning of thalamocortical connections

AU - Kashani, Amir H.

AU - Qiu, Zilong

AU - Jurata, Linda

AU - Lee, Soo-Kyung

AU - Pfaff, Samuel

AU - Goebbels, Sandra

AU - Nave, Klaus Armin

AU - Ghosh, Anirvan

PY - 2006/8/9

Y1 - 2006/8/9

N2 - Lasting changes in neuronal connectivity require calcium-dependent gene expression. Here we report the identification of LIM domain-only 4 (LMO4) as a mediator of calcium-dependent transcription in cortical neurons. Calcium influx via voltage-sensitive calcium channels and NMDA receptors contributes to synaptically induced LMO4-mediated transactivation. LMO4-mediated transcription is dependent on signaling via calcium/calmodulin-dependent protein (CaM) kinase IV and microtubule-associated protein (MAP) kinase downstream of synaptic stimulation. Coimmunoprecipitation experiments indicate that LMO4 can form a complex with cAMP response element-binding protein (CREB) and can interact with cofactor of LIM homeodomain protein 1 (CLIM1) and CLIM2. To evaluate the role of LMO4 in vivo, we examined the consequences of conditional loss of lmo4 in the forebrain, using the Cre-Lox gene-targeting strategy. The organization of the barrel field in somatosensory cortex is disrupted in mice in which lmo4 is deleted conditionally in the cortex. Specifically, in contrast to controls, thalamocortical afferents in conditional lmo4 null mice fail to segregate into distinct barrel-specific domains. These observations identify LMO4 as a calcium-dependent transactivator that plays a key role in patterning thalamocortical connections during development.

AB - Lasting changes in neuronal connectivity require calcium-dependent gene expression. Here we report the identification of LIM domain-only 4 (LMO4) as a mediator of calcium-dependent transcription in cortical neurons. Calcium influx via voltage-sensitive calcium channels and NMDA receptors contributes to synaptically induced LMO4-mediated transactivation. LMO4-mediated transcription is dependent on signaling via calcium/calmodulin-dependent protein (CaM) kinase IV and microtubule-associated protein (MAP) kinase downstream of synaptic stimulation. Coimmunoprecipitation experiments indicate that LMO4 can form a complex with cAMP response element-binding protein (CREB) and can interact with cofactor of LIM homeodomain protein 1 (CLIM1) and CLIM2. To evaluate the role of LMO4 in vivo, we examined the consequences of conditional loss of lmo4 in the forebrain, using the Cre-Lox gene-targeting strategy. The organization of the barrel field in somatosensory cortex is disrupted in mice in which lmo4 is deleted conditionally in the cortex. Specifically, in contrast to controls, thalamocortical afferents in conditional lmo4 null mice fail to segregate into distinct barrel-specific domains. These observations identify LMO4 as a calcium-dependent transactivator that plays a key role in patterning thalamocortical connections during development.

KW - Barrel cortex

KW - Calcium

KW - Cortex

KW - Development

KW - LMO4

KW - Transcription

UR - http://www.scopus.com/inward/record.url?scp=33748197014&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33748197014&partnerID=8YFLogxK

U2 - 10.1523/JNEUROSCI.0618-06.2006

DO - 10.1523/JNEUROSCI.0618-06.2006

M3 - Article

VL - 26

SP - 8398

EP - 8408

JO - Journal of Neuroscience

JF - Journal of Neuroscience

SN - 0270-6474

IS - 32

ER -