Expression of Cux‐1 and Cux‐2 in the subventricular zone and upper layers II–IV of the cerebral cortex

Abstract

Little is known about how neurons in the different layers of the mammalian cerebral cortex are specified at the molecular level. Expression of two homologues of the Drosophila homeobox Cut gene, Cux-1 and Cux-2, is strikingly specific to the pyramidal neurons of the upper layers (II-IV) of the murine cortex, suggesting that they may define the molecular identity of these neurons. An antibody against Cux-1 labels the nucleus of most of the postmitotic upper layer neurons but does not label parvoalbumin-positive cortical interneurons that derive from the medial ganglionic eminence. Cux-1 and Cux-2 represent early markers of neuronal differentiation; both genes are expressed in postmitotic cortical neurons from embryonic stages to adulthood and in the proliferative regions of the developing cortex. In precursors cells, Cux-1 immunoreactivity is weak and diffuse in the cytoplasm and nucleus of ventricular zone (VZ) cells, whereas it is nuclear in the majority of bromodeoxyuridine (BrdU)-positive subventricular zone (SVZ) dividing cells, suggesting that Cux-1 function is first activated in SVZ cells. Cux-2 mRNA expression is also found in the embryonic SVZ, overlapping with BrdU-positive dividing precursors, but it is not expressed in the VZ. A null mutation in Pax-6 disrupts Cux-2 expression in the SVZ and Cux-1 and Cux-2 expression in the postmigratory cortical neurons. Thus, these data support the existence of an intermediate neuronal precursor in the SVZ dedicated to the generation of upper layer neurons, marked specifically by Cux-2. The patterns of expression of Cux genes suggest potential roles as determinants of the neuronal fate of the upper cortical layer neurons.

Expression of Cux‐1 and Cux‐2 in the developing somatosensory cortex of normal and barrel‐defective mice

“…From P21, Cux-2 mRNA was also expressed in the cingulate cortex ( Fig. 1F) (Nieto et al, 2004). A strong expression of Cux-2 was also noted at the level of the claustrum (not shown).…”

“…Cux-1 and Cux-2 are early markers of neuronal differentiation; both genes are expressed in postmitotic neurons at early embryonic stages. Cux-1 and Cux-2 are also expressed in proliferative zones of the cerebral cortex, with selective Cux-2 expression in SVZ progenitors (Nieto et al, 2004;Zimmer et al, 2004). Interestingly, Pax6 mutant mice show a loss of Cux-2-positive cells in the SVZ as well as a loss of Cux-1 and Cux-2 in the upper layer neurons, supporting the SVZ origin of the glutamatergic neurons in layers II-IV of the neocortex (Nieto et al, 2004;Zimmer et al, 2004).…”

The determination of projection neuron identity in the developing cerebral cortex

“…However, this view has been challenged first based on histological studies [16], and subsequently by the observation that SVZ cells show patterns of gene expression that are echoed by those in upper layer neurons. For example, the noncoding RNA Svet1 and several homodomain genes, including Cux1 and Cux2 are expressed both in the SVZ and in layers 2-4 [17,18]. These corresponding patterns of gene expression suggested that upper layer neurons might be derived from the SVZ.…”

Neuronal stem cells in the central nervous system and in human diseases

“…IPC then divides symmetrically to generate two neurons or two additional IPCs (Wu and Cepko, 1993;Haubensak et al, 2004;Miyata et al, 2004;Noctor et al, 2004Noctor et al, , 2007a. Therefore, embryonic SVZ is increasingly considered as a major site of neurogenesis, whereas symmetric division is recognized to transit amplifying division (Miyata et al, 2001(Miyata et al, , 2004Tarabykin et al, 2001;Smart et al, 2002;Nieto et al, 2004;Noctor et al, 2004Noctor et al, , 2007bZimmer et al, 2004;Martínez-Cerdeño et al, 2006).…”