Expression of LIM Protein GenesLmo1, Lmo2,andLmo3in Adult Mouse Hippocampus and Other Forebrain Regions: Differential Regulation by Seizure Activity

Abstract

The LIM domain is a zinc-binding amino acid motif that characterizes various proteins which function in protein-protein interactions and transcriptional regulation. Expression patterns of several LIM protein genes are compatible with roles in vertebrate CNS development, but little is known about the expression, regulation, or function of LIM proteins in the mature CNS. Lmo1, Lmo2, and Lmo3 are LIM-only genes originally identified as putative oncogenes that have been implicated in the control of cell differentiation and are active during CNS development. Using in situ hybridization for mRNA and immunohistochemical detection of reporter protein expression in transgenic mice, we found that Lmo1, Lmo2, and Lmo3 show individually unique but partially overlapping patterns of expression in several regions of the adult mouse forebrain, including hippocampus, caudate putamen, medial habenula, thalamus, amygdala, olfactory bulb, hypothalamus, and cerebral cortex. In the hippocampal formation, Lmo1, Lmo2, and Lmo3 show different combinatorial patterns of expression levels in CA pyramidal and dentate granule neurons, and Lmo1 is present in topographically restricted subpopulations of astrocytes. Kainic acid-induced limbic seizures differentially regulated Lmo1, Lmo2, and Lmo3 mRNA levels in hippocampal pyramidal and granule neurons, such that Lmo1 mRNA increased, whereas Lmo2 and Lmo3 mRNAs decreased significantly, with maximal changes at 6 hr after seizure onset and return to baseline by 24 hr. These findings show that Lmo1, Lmo2, and Lmo3 continue to be expressed in the adult mammalian CNS in a cell type-specific manner, are differentially regulated by neuronal activity, and may thus be involved in cell phenotype-specific regulatory functions.

The oncogenic LIM-only transcription factor Lmo2 regulates angiogenesis but not vasculogenesis in mice

“…2C). These ␤-galactosidase expression data are compatible with Lmo2 expression patterns observed with RNA in situ hybridization (25)(26)(27)(28), indicating that the expression of ␤-galactosidase in endothelial cells is also a true reflection of Lmo2 promoter activity in embryogenesis.…”

LMO4 can interact with Smad proteins and modulate transforming growth factor-β signaling in epithelial cells

“…Our data, which suggest that TGFb regulation of at least some genes may be sensitive to LMO4 levels, are likely to have implications for understanding LMO4-mediated gene regulation because LMO4 is highly regulated under a variety of conditions that include normal and cancer development, as well as in response to physiological stimuli (Hinks et al, 1997;Wang et al, 2004). Owing to the cell-and developmental-specific regulation of LMO4, our findings may provide a mechanistic basis for aspects of cell-type-and context-specific gene regulation by TGFb.…”

Dynamic spatiotemporal expression of LIM genes and cofactors in the embryonic and postnatal cerebral cortex

“…Lmo genes, expressed in distinct patterns in the adult mouse hippocampus, are regulated in seizure, implicating them in cell phenotype-specific regulatory functions in maturity (Hinks et al, 1997).…”