Calcium activation of the LMO4 transcription complex and its role in the patterning of thalamocortical connections.
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.
Kashani
Amir H
AH
Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Qiu
Zilong
Z
Jurata
Linda
L
Lee
Soo-Kyung
SK
Pfaff
Samuel
S
Goebbels
Sandra
S
Nave
Klaus-Armin
KA
Ghosh
Anirvan
A
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D019521:Body Patterning / Q000502:physiology*; D002118:Calcium / Q000502:physiology*; D020013:Calcium Signaling / Q000502:physiology*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000502:physiology*; D018398:Homeodomain Proteins / Q000378:metabolism*; D060588:LIM Domain Proteins; D051379:Mice; D009434:Neural Pathways / Q000166:cytology / Q000196:embryology / Q000502:physiology; D051381:Rats; D020318:Rats, Long-Evans; D013788:Thalamus / Q000166:cytology / Q000196:embryology* / Q000502:physiology*; D014018:Tissue Distribution; D014157:Transcription Factors / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D018398:Homeodomain Proteins; D060588:LIM Domain Proteins; C491976:Lmo4 protein, mouse; D014157:Transcription Factors; D002118:Calcium