Transient expression of Xpn, an XLMR protein related to neurite extension, during brain development and participation in neurite outgrowth

Abstract

KIAA2022 has been implicated as a gene responsible for expressing X-linked mental retardation (XLMR) proteins in humans. However, the functional role of KIAA2022 in the human brain remains unclear. Here, we revealed that depletion of Kiaa2022 inhibits neurite outgrowth of PC12 cells, indicating that the gene participates in neurite extension. Thus, we termed Kiaa2022 as an XLMR protein related to neurite extension (Xpn). Using the mouse brain as a model and ontogenetic analysis of Xpn by real-time PCR, we clearly demonstrated that Xpn is expressed transiently during the late embryonic and perinatal stages. In situ hybridization histochemistry further revealed that Xpn-expressing neurons could be categorized ontogenetically into three types. The first type showed transient expression of Xpn during development. The second type maximally expressed Xpn during the late embryonic or perinatal stage. Thereafter, Xpn expression in this type of neuron decreased gradually throughout development. Nevertheless, a significant level of Xpn expression was detected even into adulthood. The third type of neurons initiated expression of Xpn during the embryonic stage, and continued to express the gene throughout the remaining developmental stages. Subsequent immunohistochemical analysis revealed that Xpn was localized to the nucleus and cytoplasm throughout brain development. Our findings indicate that Xpn may participate in neural circuit formation during developmental stages via nuclear and cytoplasmic Xpn. Moreover, disturbances of this neuronal circuit formation may play a role in the pathogenesis of mental retardation.