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academies

August 16-17, 2018 | Copenhagen, Denmark

Dementia and Alzheimer ’s Disease

10

th

World congress on

Journal of Neurology and Neurorehabilitation Research | Volume: 3

Electric axon guidance in embryonic retina: Involvement of integrins

Masayuki Yamashita

Center for Medical Science, Japan

T

he axons of embryonic brain, spinal cord, and retina extend

along the extracellular voltage gradient towards the cathode

in a process known as galvanotropism. In embryonic nervous

tissues, positive direct current (DC) potentials are generated by

neuroepithelial cell’s sodium transport1, of which disruption

results in erroneous axon path-finding4, suggesting that electric

fields play a pivotal role in orienting newborn axons. However,

the experimental evidence was lacking for the cell surface

molecule that is activated asymmetrically in an electric field.

Here I show that integrin activation mediates electric axon

guidance. Retinal strips of chick embryos were embedded

in Matrigel®, and cultured in the electric field of the same

strength as that in vivo (15 mV/mm)4. Matrigel® contained the

same extracellular matrix proteins as in the embryonic retina,

laminin and collagen, to which integrins bind. Retinal ganglion

cell axons extended towards the cathode2. A monoclonal anti-

chicken integrin antibody (TASC), which enhances integrin-

ligand binding, accelerated the cathodal growth. A reduction

in the extracellular free Ca2+ with EGTA also enhanced the

cathodal growth, which suggested that millimolar Ca2+ inhibits

axon growth, and also that the influx of Ca2+ was unlikely to

be essential for cathodal steering. In the presence of Mn2+,

which non-specifically activates integrin-ligand binding, the

axons formed local meshes. These results suggested that the

inhibition of integrins by the extracellular Ca2+ underlies

electric axon guidance.

Recent Publications:

1. Yamashita M (2016) Epithelial sodium channels (ENaC)

produce extracellular positive DC potentials in the retinal

neuroepithelium. Data in Brief, 6: 253-256.

2. Yamashita M (2015) Weak electric fields serve as

guidance cues that direct retinal ganglion cell axons in vitro.

Biochemistry and Biophysics Reports, 4: 83-88.

3. Yamashita M (2015) Electrophysiological recordings from

neuroepithelial stem cells. Stem Cell Renewal and Cell-Cell

Communication (Ed. Turksen K), Methods in Molecular

Biology, Springer Protocols, 1212: 195-200.

4. Yamashita M (2013) Electric axon guidance in embryonic

retina: Galvanotropism revisited. Biochem Biophys Res

Commun, 431: 280-283.

5. Yamashita M (2013) From neuroepithelial cells to neurons:

Changes in the physiological properties of neuroepithelial

stem cells. Arch Biochem Biophys, 534: 64-70.

6. Yamashita M (2012) Ion channel activities in neural stem

cells of the neuroepithelium. Stem Cells International, 2012:

doi: org/10.1155/2012/247670.

Speaker Biography

Masayuki Yamashita is a professor of physiology at International University of

Health and Welfare. He received his PhD at the Department of Neurophysiology,

Institute of Brain Research, School of Medicine, University of Tokyo in 1986. He

moved to National Institute for Physiological Sciences (Okazaki, Japan) as a JSPS

fellow and a research associate. In 1989, he started physiological studies of retina

at the Department of Neuroanatomy, Max-Planck-Institute for Brain Research

(Frankfurt/M). After the reunification of Germany, he moved to the Department

of Physiology, Osaka University Medical School. He studied the calcium signaling

systems in embryonic chick retina. Then, he moved to the Department of Physiology,

Nara Medical University as a professor (1999-2014). He has been interested in the

electrophysiological properties of neuroepithelial cells and newborn neurons. The

retina is a nice model for studying the early development of central nervous systems.

e:

my57@iuhw.ac.jp