Laminar and Areal Expression of Unc5d and Its Role in Cortical Cell Survival

Abstract

The UNC-5 family of netrin receptors is known to regulate axon guidance, cell migration, and cell survival. We have previously demonstrated that unc5d, one of the UNC-5 family member genes, is specifically expressed in layer 4 of the developing rat neocortex (Zhong Y, Takemoto M, Fukuda T, Hattori Y, Murakami F, Nakajima D, Nakayama M, Yamamoto N. 2004. Identification of the genes that are expressed in the upper layers of the neocortex. Cereb Cortex. 14:1144-1152). However, the role of UNC5D in cortical development is still unknown. In this study, we revealed that unc5d was highly expressed in the primary sensory areas of the mouse neocortex at around postnatal day 7. Netrin-4 was also found to be predominantly expressed in layer 4 of the sensory cortex and sensory thalamic nuclei. Cell surface binding assay showed that netrin-4 protein bound to UNC5D-expressing cells. An in vitro study further demonstrated that cell death of unc5d-expressing layer 4 cells was reduced by exogenous application of netrin-4 protein, whereas UNC5D is not sufficient to mediate the effect of netrin-4 in deep layer cells. Taken together, these results suggest that UNC5D is primarily expressed by layer 4 cells in the primary sensory areas of the developing neocortex and may mediate the effect of netrin-4 on cortical cell survival in a lamina-specific manner.

Behavioral Abnormalities and Circuit Defects in the Basal Ganglia of a Mouse Model of 16p11.2 Deletion Syndrome

“…In the cortex (Figure 3C), we found gene clusters that distinguish progenitor populations, cortical interneurons, and distinct groups of cortical excitatory neurons. Among these are deeper layer excitatory neurons that are born earliest during corticogenesis and already express mature markers indicating synaptogenesis, upper layer excitatory neurons generated late in embryogenesis, and ventricular zone (VZ) progenitors, which in the neonate also start to express glial progenitor markers (Arlotta et al, 2005, Chen et al, 2008, Lai et al, 2008 Molnár and Cheung, 2006 Sasaki et al, 2008 and Takemoto et al, 2011). This analysis strategy therefore identified gene clusters correlating with specific cell types previously described using other methods in vivo.…”

RNA-seq based transcriptomic map reveals new insights into mouse salivary gland development and maturation

“…For example after mining our embryo enriched dataset, we identified several genes which showed peak expression levels very early during salivary gland morphogenesis and then declined over the course of late embryonic development and into adult. While several of the highly differentially expressed genes at E14.5 have been implicated in axonal guidance such as Unc5d [64] and Tubb2b [65], we also identified additional genes from this group that may be interesting for future follow up studies including Scube1 [66] and Dlx1 [67], both of which have been implicated in craniofacial development but not in salivary gland biology. Needless to say, RNA-seq based analysis similar to those described in this work can be further extended to additional time points during mouse embryogenesis, in particular at stages earlier than E12.5 during which the salivary gland fate is being established.…”

Exome sequencing identifies a novel UNC5D mutation in a severe myopic anisometropia family

“…The detail information and clinical characters of eyes have been showed in our previous report [24] (Supplemental Table 1). The family comprised 20 individuals, of whom 18 participated in this study.…”