Some of these cells undergo two waves of migration—one rostrally to form the nucleus

posterior limitans (PLi) and the lateral habenula selleck chemicals (LHa) and the other ventrally into the ventral LGN which is largely populated by Dlx-expressing cells. The expression of Dlx in the vLGN offers a repulsive signal to the invading Sox14 cells, thus ensuring only a few Sox14 cells populate the vLGN. In the absence of Dlx1/2 this repulsive signal is abolished leading to mass migration of Sox14 cells into the vLGN turning it into an IGL phenotype territory ( Figure 1A). The Sox14-deficient mice in which the Sox14 coding sequence is replaced by GFP show no significant changes in the overall organization of the SVS except for the redistribution of cell populations in the IGL/vLGN region. The presumptive Sox14 cells fail to migrate ventrally to partially populate the vLGN and remain in the IGL region (Figure 1A), increasing their density. Sox14 appears to be dispensable for expression

of Gad1 and NPY suggesting the Sox14-deficient cells are still neurotransmitter competent. An increased density of Sox14-GFP cells in the IGL also correlated with increased immunoreactivity for NPY. Taken together, the combined function of Sox14 and Dlx define the spatial distribution of Sox14-expressing cells in the IGL and vLGN region of the SVS. The loss of Sox14 leads to changes in the regional distribution of Sox14 cells and consequently nearly potential changes in the pattern and strength of connectivity of IGL with INCB024360 purchase target regions. To assess the functional consequence of the loss of Sox14 expression, Delogu et al. (2012) used a suite of behavioral tests. Intact pupillary light reflex and

light induction of c-Fos in the SCN implied normal ontogeny and projection of the ipRGCs in these mice. The circadian activity rhythm under constant darkness also showed normal periodicity, thus indicating no gross defect in the endogenous SCN clock. However, the Sox14 knockout mice showed profound alteration in activity-rest pattern. Several studies have demonstrated the IGL participates in at least three different aspects of daily arousal-rest pattern: overall activity level, entrainment of the circadian clock, and light suppression of activity or masking. Since the loss of Sox14 affects the cellular composition of the IGL and consequently changes the circuitry, the mice show remarkable defects in all three aspects of activity regulation. Increased number of functionally active NPY-positive cells in the IGL and potentially increased NPY-mediated signaling is opposite to IGL lesion resulting in reduced activity (Redlin et al., 1999). Overall, the Sox14 knockout mice appear to exhibit increased basal activity. Light is known to enhance NPY release from the GHT at the SCN, thereby driving early morning NPY release near the SCN (Glass et al., 2010).