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

Abstract

LIM-homeodomain (LIM-HD) genes encode a family of transcription factors known to be involved in development and patterning in several systems. Previously, we have shown that LIM-HD gene Lhx2 is required for the formation of a crucial boundary in the dorsal telencephalon (Bulchand et al. [2001] Mech Dev 100:165-175). To further explore the role of LIM-HD genes as well as the broader LIM gene family in dorsal telencephalic development, we examined the expression pattern of the members of this gene family and their cofactors in the developing mouse cerebral cortex. Transcription factor activity of the LIM-HD proteins requires the formation of a tetrameric complex consisting of two LIM-HD molecules linked by a dimer of cofactor (Clim) molecules. LIM-only (Lmo) proteins can interfere with this process by competing for the cofactors. LIM-HD protein function, thus, can be modulated by the presence of the appropriate Clim or Lmo molecules. At least 13 LIM-HD, 4 Lmo, and 2 Clim genes have been identified in the mouse. Several of these genes exhibit complex spatiotemporal patterns spanning different stages of cortical development, from embryonic to postnatal ages. Noteworthy features of the expression patterns include delineation of boundaries within the developing cortex, up- or down-regulation during formation of selected cortical layers, and a striking complementarity of expression of several members consistent with specific functions in cortical development. Significantly, in some cases, Lmo or Clim gene expression is robust where no LIM-HD gene expression is detectable. These results suggest multiple and distinct roles for LIM-HD, Lmo, and Clim genes in cortical development, and also support a LIM-HD-independent role for some Lmo and Clim members.