Naoko Koyano Nakagawa, Ph.D.

Education

Dr. Koyano-Nakagawa is an assistant professor in the Department of Neuroscience and a member of the Stem Cell Institute. She received her Ph.D. from the University of Tokyo, Japan, studying cytokine gene regulation under the direction of Drs. Ken-ichi Arai and Takashi Yokota. She worked with Dr. Chris Kintner as a postdoctoral fellow at the Salk Institute for Biological Studies and investigated functions and regulatory mechanisms of neuronal transcription factors neurogenin and Hes6.

Research Interests

My lab aims to understand the functions of transcription factors regulating differentiation of neurons from neural stem cells.

There are at least two mechanisms that regulate the formation of neurons, namely pan-neuronal and cell type-specific mechanisms. The former endows general properties common to all neurons, for instance, choice of neuronal fate instead of others, withdrawal from the cell cycle, expression of general neuronal markers, and axon extension.

The latter defines traits of each subset of neurons. Gene cascades regulating each process as well as how these processes interact with each other are major questions in developmental neurobiology.

We focus on analyzing the pan-neuronal aspect of neurogenesis using Xenopus laevis and chick embryos as model systems. Group of genes that are pan-neuronally expressed are usually expressed in a defined time frame. We hypothesize that there are cascade of events that occur once differentiation program is initiated, and the tight temporal regulation of factors involved in this process is essential for differentiation to proceed.

Genes have to be turned on properly and also have to be shut off timely for cells to progress to the next developmental stage. There are two main approaches we take to analyze gene regulatory mechanism.

 First, we approach from the transcription factor side by isolating and characterizing downstream targets of frog neurogenin, one of the master neurogenic genes. Of current particular interest is MTG family of transcription factors, whose members regulate different steps of neuronal differentiation. We take gain-of-function and loss-of-function approaches as well as further cloning of interaction molecules to characterize the function of MTG proteins.

The second approach is from the promoter side. We identify regulatory elements of pan-neuronal genes to reveal the mechanism of developmental progression.

Selected Publications

• Schlosser, G., Koyano-Nakagawa, N., and Kintner, C. (2002). Thyroid hormone promotes neurogenesis in the Xenopus spinal cord. Developmental Dynamics 225, 485-498.

• Koyano-Nakagawa, N., Kim, J., Anderson, D., and Kintner, C. (2000) Hes6 acts in a positive feedback loop with the neurogenins to promote neuronal differentiation. Development 127, 4203-4216.

• Koyano-Nakagawa, N., Wettstein, D., and Kintner, C. (1999) Activation of Xenopus genes required for lateral inhibition and neuronal differentiation during primary neurogenesis. Molec. Cell. Neurosci. 14, 327-339.

• Deblandre, G. A., Wettstein, D. A., Koyano-Nakagawa, N., and Kintner, C. (1999) A two-step mechanism generates the spacing pattern of the ciliated cells in the skin of Xenopus embryos. Development 126, 4715-4728.

• Kao, H. Y., Ordentlich, P., Koyano-Nakagawa, N., Tang, Z., Downes, M., Kintner, C. R., Evans, R. M., and Kadesch, T. (1998) A histone deacetylase corepressor complex regulates the Notch signal transduction pathway. Genes Dev 12, 2269-77.