학술논문

Calcium regulation of LMO4-mediated transcription and its role in thalamocortical development.
Document Type
Theses
Source
Dissertation Abstracts International; Dissertation Abstract International; 67-04B.
Subject
Biology, Molecular
Biology, Neuroscience
Language
English
Abstract
Summary: Lasting changes in neuronal connectivity require calcium-dependent gene expression. Using the Transactivator Trap approach we identified 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 transactivation is mediated, at least in part, by signaling via the CaM kinase pathway downstream of synaptic stimulation. These findings suggest that LMO4 may play a role in activity dependent cortical development. 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. LMO4 conditional mice are viable and fertile and the CNS is grossly normal. Interestingly, cytochrome oxidase staining of the cortex reveals that the segregation of thalamic axons in barrel cortex is markedly disrupted in conditional LMO4 knockout mice. These observations indicate that LMO4 is a calcium regulated transactivator that plays a critical role in neonatal cortical development.