COUP-TFI: an intrinsic factor for early regionalization of the neocortex

Abstract

Regionalization of the cerebral cortex is thought to involve two phases: an early regionalization phase and a later refinement phase. It has been shown that early regionalization of the neocortex does not require thalamic inputs and is regulated by intrinsic factors. Recently, two such intrinsic factors, Pax6 and Emx2, have been identified. In this study, we identified COUP-TFI as a regulatory factor for early neocortical regionalization. The spatial and temporal expression pattern of COUP-TFI suggested a role in specification of the neocortex and in maintaining cortical identity. Altered region-specific expression of marker genes in the cortex as well as miswired area-specific connections between the cortex and the thalamus in COUP-TFI null mice indicate COUP-TFI plays a critical role in regulating early regionalization. Our results substantiate that COUP-TFI, an intrinsic factor, may work in concert with Pax6 and Emx2 to specify neocortical identity.

The expression pattern of nuclear receptors during cerebellar development

“…In general, COUP-TFI is more highly expressed in the neuronal tissue of the central and peripheral nervous systems, whereas COUP-TFII is expressed in the mesenchyme of developing organs (Pereira et al, 1995). Loss of function assays indicate that COUP-TFI is important for neurogenesis and neural crest cell differentiation during embryonic development Zhou et al, 2001;Yamaguchi et al, 2004), while COUP-TFII acts as a major regulator of angiogenesis, vein identity, and organ development (Pereira et al, 1999;Takamoto et al, 2005;You et al, 2005). In the cerebellum, the expressions patterns of these two receptors are not co-localized.…”

Requirement of the orphan nuclear receptor SF-1 in terminal differentiation of ventromedial hypothalamic neurons

“…Similarly, the orphan nuclear receptor RORα is crucial for maturation and survival of Purkinje cells in the cerebellum (Dussault et al, 1998;Chu and Zingg, 1999;Vogel et al, 2000). Finally, the inhibitory orphan receptor, COUP-TFI, is known to mediate neocortex identity as suggested by the loss of regional organization and specific gene expression in the absence of COUP-TFI function (Zhou et al, 2001). In the absence of bona fide ligands, potential mechanisms for regulating these orphan receptors include posttranslational phosphorylation and selective recruitment of coactivator proteins, as shown for SF-1 (Hammer et al, 1999;Ito et al, 2000;Desclozeaux et al, 2002).…”

Gradients in the Brain: The Control of the Development of Form and Function in the Cerebral Cortex

“…3B). The roles of COUP-TFI in cortical development have been studied in germline and cortexspecific mutant mice, and have also been investigated by in vivo overexpression (Zhou et al 2001;Armentano et al 2007;Faedo et al 2008). In mice with a cortex-specific deletion of COUP-TFI, the expression of regional cortical plate markers Cdh8, Id2, Fezf2, and Efna5 revealed that the balance of area pattern was changed such that the majority of the cortex was transformed into motor cortex, and the somatosensory and visual areas were greatly reduced in size and located at the caudal pole of the structure (Fig.…”

“…The orphan nuclear receptor COUP-TFI is a transcription factor expressed in a caudomedialhigh to rostrolateral-low gradient in the developing neocortex (Zhou et al 2001) (Fig. 3B).…”