Motoyama Research Unit
Research Areas
| Our objective is to develop preventive measure for the brain malformation during pregnancy. We focus on the sonic hedgehog (SHH) signaling which is essential for cell-to-cell interaction during mammalian brain development. In humans, mis-regulation of this signaling is closely related to brain defects, mental retardation and brain tumors. Our laboratory has been using the mouse as a model to study the role of SHH signaling during brain development and in the adult brain. The SHH signaling has been shown as necessary to specify the midline structure of the brain. However, little is known about the pathogenesis of the human diseases such as holoprosencephaly, exencephaly and medulloblastomas caused by mutations in SHH signaling. We are currently using targeted mutant mice, which have the similar mutations as those found in these human diseases. Furthermore we investigate the action of environmental factors affecting SHH signaling during brain development. By studying the etiology of the abnormalities caused by genetic and environmental factors, we attempt to understand the mechanisms of the brain development and we would like to contribute to develop the way to protect developing brain during pregnancy. |  Unit Leader Jun MOTOYAMA (Ph.D.)  |
Research Subjects
| (1) | Role of SHH signaling in the proliferation of neuronal stem cells |
| (2) | Role of SHH signaling cascade during developing brain |
| (3) | Molecular pathogenesis of brain defects by the environmental risk factors |
| (4) | Protection of developing brain from genetic and environmental risks |
List of Selected Publications
| (1) | Aoto, K., Nishimura, T., Eto, K., and Motoyama, J.: "Mouse Gli3 regulates FGF8 expression and apoptosis in the developing neural tube, face and limb bud." Developmental. Biology., 251, 320-332 (2002). |
| (2) | Motoyama, J., Milenkovic, L., Iwama, M., Shikata, Y., Scott, M.P., and Hui, C.-c.: "Differential requirement for Gli2 and Gli3 in ventral neural cell fate specification." Developmental Biology, 259, 150-161 (2003). |
| (3) | Motoyama, J., and Aoto, K.: "Important role of Shh controlling Gli3 functions during the dorsal-ventral patterning of the telencephalon." Hedgehog-Gli Signaling in Human Disease, Chapter 14, 177-183 (2006). Landes Bioscience/Eurekah.com, Springer Science+Business Media, Inc. Texas. |
| (4) | Motoyama, J.: "Essential roles of Gli3 and sonic hedgehog in pattern formation and developmental anomalies caused by their dysfunction." Congenit Anom. 46, 123-128 (2006). |
| (5) | Nieuwenhuis, E., Motoyama, J., Barnfield, P.C., Yoshikawa, Y., Zhang, X., Mo, R., Crackower, M.C., and Hui, C.c.: "Mice with a targeted mutation of Patched2 are viable but develop alopecia and epidermal hyperplasia." Mol Cell Biol. 26, 6609-6622 (2006). |
| (6) | Aoto, K., Yayoi, S., Higashiyama, D., Shiota, K., and Motoyama, J.: "Fetal Ethanol Exposure Activates Protein Kinase A and Impairs Shh Expression in Prechordal Mesendoderm Cells in the Pathogenesis of Holoprosencephaly." Birth Defects Research Part A: Clinical and Molecular Teratology 82, 224-231 (2008). |
| (7) | Okada, T., Okumura, Y., Motoyama, J., and Ogawa, M.: "Fgf8 signaling patterns the telencephalic midline by regulating putative key factors of midline development." Developmental Biology 320, 92-101 (2008). |
| (8) | Aoto, K., Shikata, Y., Imai, H., Matsumaru, D., Tokunaga, T., Shioda, S., Yamada, G., and Motoyama, J.: "Mouse Shh is required for prechordal plate maintenance during brain and craniofacial morphogenesis." Developmental Biology (in press 2009). |