Stem Cell and Neuro-Vascular Development and Patterning Section

Yosuke Mukoyama, PhD, Principal Investigator

Nerves and blood vessels provide a vital network among tissues. Our research focuses on interactions between developing nervous system and vascular system, particularly neuronal influences on angiogenesis and vascular influences on neurogenesis and stem cell maintenance. We study how nerve controls blood vessel identity (artery and vein) and branching pattern during development. We are trying to understand how blood vessels function as a stem cell niche. We utilize a broad range of techniques encompassing fluorescence-activated-cell sorting (FACS), microarray analyses, loss- and gain-of-function genetic manipulations in mouse, rat and chicken to identify the signals to coordinate the interactions of these two systems.

Image	Description
	Figure 1. Nerves (green) associate with arteries (red) in the embryonic limb skin.
	Figure 2. Motoneurons and their progenitors (green) are surrounded by blood vessels (red) in the embryonic spinal cord.
	Figure 3. Transplanted murine motoneuron progenitors (green) differentiate motoneurons that project axons (labeled by anti-Tuj1 antibody, red) from the ventral root of the chick spinal cord.

SELECTED PUBLICATIONS

(Cardiovascular development)
GREGO-BESSA, J., LUNA-ZURITA, L., DEL MONTE, G., BOLÓS, V., MELGAR, P., ARANDILLA, A., GARRATT, AN., ZANG, H., MUKOUYAMA, Y., CHEN, H., SHOU, W., BALLESTAR, E., ESTELLER, M., ROJAS, A., PÉREZ-POMARES, JM., DE LA POMPA, JL. (2007) Notch signaling is essential for ventricular chamber development. Dev Cell. 3:415-29.

(Nerve-blood vessel alignment)
MUKOUYAMA, Y., GERBER, H., FERRARA, N., GU, C. AND ANDERSON, D.J. (2005). Peripheral nerve-derived VEGF promotes arterial differentiation via neuropilin-1-mediated positive-feedback. Development 132 :941-952.

MUKOUYAMA, Y., SHIN, D., BRITSCH, S., TANIGUCHI, M., AND ANDERSON, D.J. (2002) Sensory nerves determine the pattern of arterial differentiation and blood vessel branching in the skin. Cell 109: 693-705.

(Neural stem cells and neurogenesis)
MUKOUYAMA, Y., DENEEN, B., LUKASZEXICZ, A., NOVITCH, B.G., WICHTERLE, H., JESSELL, T.M., AND ANDERSON, D.J. (2006) Olig2+ neuroepithelial motoneuron progenitors are not multipotent stem cells in vivo. Proc Natl Acad Sci U S A. 103(5):1551-6.

(Hematopoiesis)
MUKOUYAMA, Y., CHIBA, N., MUCENSKI, M. L., SATAKE, M., MIYAJIMA, A., HARA, T AND WATANABE, T. (1999). Hematopoietic cells in cultures of the murine embryonic aorta-gonad-mesonephros region are induced by c-Myb. Current Biology 9:833-836.

MUKOUYAMA, Y., HARA, T., XU, M., TAMURA, K., DONOVAN, P.J., KIM, H., KOGO, H., TSUJI, K., NAKAHATA, T AND MIYAJIMA, A. (1998). In vitro expansion of murine multipotential hematopoietic progenitors derived from the embryonic aorta gonad mesonephros region. Immunity 8:105-114.

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