Identification and characterization of a novel axon guidance receptor in the eye-specific visual projection

Correct functioning of the nervous system critically depends on the formation of the precise neuronal network. In mammals with binocular vision, axons of retinal ganglion cells from the right and left eyes project to different domains of the lateral geniculate nucleus in the thalamus (Retinogeniculate projection). The eye-specific visual projection provides the anatomical basis for disparity-based stereopsis (perception of depth). However, the molecular mechanism that regulates the eye-specific visual projection is not well understood. Nell2 (neural epidermal growth factor (EGF)-like-like 2) is an extracellular glycoprotein that is predominantly expressed in the nervous system. Our lab has previously shown that Nell2 acts as an inhibitory axon guidance molecule in establishment of the eye-specific retinogeniculate projection. The current work aims to identify and functionally characterize the receptor molecule that transduces Nell2-mediated signaling in retinal ganglion cells. By using immunohistochemistry, we found that the receptor tyrosine kinase Ros1, which is known to bind the Nell2, is expressed in developing chick retinal ganglion cells., suggesting that Ros1 may act as a receptor for Nell2 in the visual projection. We are currently generating gene knock-down constructs for Ros1, which will be used in in vitro and in vivo axon guidance assays. We expect that this project will elucidate the function of Nell2-Ros1 interaction in establishment of the eye-specific retinogeniculate projection

Molecular Mechanisms that establish the eye-specific visual projection

Correct functioning of the nervous system critically depends on the formation of the precise neuronal network. For example, axons of retinal ganglion cells from the right and left eyes project to different domains in the lateral geniculate nucleus of the thalamus. This eye-specific retinogeniculate projection provides the anatomical basis for binocular vision. Nell2 (neural epidermal growth factor (EGF)-like-like-2) is an extracellular glycoprotein that is predominately expressed in the nervous system. Our lab has previously shown that Nell2 acts as an inhibitory axon guidance molecule in the establishment of the eye-specific retinogeniculate projection. The current work aims to identify the Nell2 receptor in the retinal axon guidance. By using immunohistochemistry, we found that the receptor tyrosine kinase Ros1, which binds to Nell2, is expressed in the developing chick retinal ganglion cells. Our results suggest that Ros1 may act as a receptor for Nell2 in the retinal ganglion cells and play a significant role in the establishment of the eye-specific retinogeniculate projection

Identification and characterization of a novel axon guidance receptor in the eye-specific visual projection

Correct functioning of the nervous system critically depends on the formation of the precise neuronal network. In mammals with binocular vision, axons of the retinal ganglion cells from the right and left eyes project to different domains of the lateral geniculate nucleus in the thalamus (Retinogeniculate projection). The eye-specific visual projection provides the anatomical basis for disparity-based stereopsis (perception of depth). However, the molecular mechanism that regulated the eye-specific visual projection is not well understood. Nell2 (neural epidermal growth factor (EGF)-like-like 2) is an extracellular glycoprotein that is predominantly expressed in the nervous system. Our lab has previously shown that Nell2 acts as an inhibitory axon guidance molecule in the establishment of the eye-specific retinogeniculate projection. The current wor aims to identify and functionally characterize the receptor molecule that transduces Nell2-mediated signaling in retinal ganglion cells. By using immunohistochemistry, we found that the receptor tyrosine kinase Ros1, which is known to bind to Nell2, is expressed in developing chick retinal ganglion cells, suggesting that Ros1 may act as a receptor for Nell2 in the visual projection, We are currently generating gene known-down constructs for Ros1, which will be used in in vitro and in vivo axon guidance assays. We expect that this project will elucidate the function of Nell2-Ros1 interaction in establishment of the eye-specific retinogeniculate projection

Expression and regulatory effects on cancer cell behavior of NELL1 and NELL2 in human renal cell carcinoma

We thank Professors Michael Rehli, Yoshiaki Ito, and Kristian Helin for gifting plasmids, Dr. Alasdair MacKenzie (University of Aberdeen) for helpful discussion, and Mr. Takashi Mizukami, Ms. Ryoko Tokuda, and Ms. Sanae Funaoka (Kanazawa University) for technical assistance.Peer reviewedPublisher PD

Complementary gradients in expression and binding of ELF-1 and Mek4 in development of the topographic retinotectal projection map

Peer reviewedPublisher PD

Cost Analysis of eVTOL Configuration Design for an Air Ambulances System in Japan

Electric-vertical-takeoff-and-landing (eVTOL) aircraft, known as urban air mobility or flying cars, are being considered for widespread use as air taxis, emergency medical transportation, sightseeing vehicles, and rural transportation, owing to their reduced-size, low-cost, and low-noise characteristics. In this study, we conduct an interview at a Japanese hospital that currently uses a helicopter for medical emergencies to output the mission profile. Due to current battery-technology limitations, the new air ambulance, which will deliver a doctor to a patient, is conceived as having 2 passengers, including the pilot. Two eVTOL configurations are studied: a fixed-wing craft and a multi-rotor. The purpose of this study is to develop a cost model for a new air ambulance through a combination of 3 approaches: top-down, bottom-up, and parametric. The cost model is constructed to analyze the production cost of each configuration, broken down into the capital expense and direct operating cost. The result shows that the multi-rotor’s production cost is lower than the fixed-wing craft. The direct operating cost of a fixed-wing craft at high flight hours is higher than that of the multi-rotor. Scenario analysis shows a result that the capacity difference of a battery has a significant difference in the cost in the years 2020 and 2030 due to the high cost of battery replacement

Understanding vertebrate embryonic development under conditions present in outer space

It is currently unknown whether humans can survive and thrive in outer space, which includes human embryonic development. In this study we investigate vertebrate embryonic development under conditions present in outer space including microgravity and an altered day-and-night cycle using zebrafish and chicken model systems. Zebrafish and chicken model systems are widely used in developmental biology research given their similarity as vertebrates to humans. We aim to analyze the development of brain, muscle and other tissues under conditions of microgravity in both zebrafish and chicken embryos. Additionally, we will analyze zebrafish development under an altered day-and-night cycle (16 sunrises and 16 sunsets per day), and determine whether adult zebrafish can survive and reproduce under these conditions. Zebrafish and chicken embryos will be placed onto a clinostat, which is a device used to simulate a microgravity environment. Embryos will be harvested between 2 and 14 days of incubation on the clinostat, and markers of cell proliferation, death, and differentiation will be analyzed on tissue sections of the brain, skeletal muscle, and other tissues. We expect that our results may allow us to better understand embryonic development under conditions present in outer space, which may shed light on this process in humans

Loss-of-function analysis of EphA receptors in retinotectal mapping

Peer reviewedPublisher PD

Expression and regulatory effects on cancer cell behavior of NELL1 and NELL2 in human renal cell carcinoma

Neural epidermal growth factor-like like (NELL) 1 and 2 constitute a family of multimeric and multimodular extracellular glycoproteins. Although the osteogenic effects of NELL1 and functions of NELL2 in neural development have been reported, their expression and functions in cancer are largely unknown. In this study, we examined expression of NELL1 and NELL2 in renal cell carcinoma (RCC) using clinical specimens and cell lines. We show that, whereas NELL1 and NELL2 proteins are strongly expressed in renal tubules in non-cancerous areas of RCC specimens, their expression is significantly downregulated in cancerous areas. Silencing of NELL1 and NELL2 mRNA expression was also detected in RCC cell lines. Analysis of NELL1/2 promoter methylation status indicated that the CpG islands in the NELL1 and NELL2 genes are hypermethylated in RCC cell lines. NELL1 and NELL2 bind to RCC cells, suggesting that these cells express a receptor for NELL1 and NELL2 that can transduce signals. Furthermore, we found that both NELL1 and NELL2 inhibit RCC cell migration, and NELL1 further inhibits RCC cell adhesion. These results suggest that silencing of NELL gene expression by promoter hypermethylation plays roles in RCC progression by affecting cancer cell behavior. We found that the down-regulation of NELL1 and NELL2 in renal cell carcinoma (RCC) is in part due to the hypermethylation of CpG islands in their putative promoter regions. Furthermore, we found that NELL1 suppresses and NELL2 partially suppresses RCC cell migration, and NELL1 further inhibits RCC cell adhesion. © 2015 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association

Neuronal pentraxins mediate synaptic refinement in the developing visual system

Peer reviewedPublisher PD