7/27/2019 Distinct Roles of Sox Family Transcription Factors in Adult

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Abstracts S5

the historical view, I will mention someproblemsthat should be addressed in future

research.

doi:10.1016/j.neures.2009.09.1488

SY1-B1-2 Distinct roles of Sox family transcription factors in adult

neurogenesis

Satoru Matsuda 1,4,5, James Hirotaka Okano 1, Shuichi Tsutsumi 2,

Hiroyuki Aburatani2

, Yumiko Saga3

, Hachiro Sugimoto4

, HideyukiOkano 1

1 Keio Univ, School of Medicine, Tokyo, Japan; 2 RCAST, Univ of Tokyo, Tokyo,

Japan; 3 National Institute of Genetics, Shizuoka, Japan; 4 Kyoto Univ, Grad-

uate School of Pharmaceutical Sciences, Kyoto, Japan; 5 JSPS, Japan

Adult neurogenesis is strictly regulated by intrinsic factors such as Sox transcrip-

tion factors. It recapitulates the process of neuronal development and of neuronal

maturation to some extents, however, precise intrinsic mechanisms remain to be

clarified. Here we show that Sox21 is required for the proper neurogenesis in hip-

pocampal dentate gyrus (DG). Sox21-deficient mice showed a dramatic decrease

of newly generated neurons and differentiation arrest of transiently amplifying

(TA) cells. Additionally, in vivo/in vitro Sox21-overexpression induced expression

of the neuronal differentiation markers. These results suggest that Sox21 functions

as a regulator of adult neurogenesis by putting TA cells into later differentiation

stages. Furthermore, we are addressing the downstream mechanism of Sox family

by performing ChIP-sequencing.

doi:10.1016/j.neures.2009.09.1489

SY1-B1-3 The significance and mechanism of adult neurogenesis

Ryoichiro Kageyama

Inst Virus Res, Kyoto Univ, Kyoto, Japan

Neurogenesis occurs continuously in the forebrain of the adult mammals, but the

functional significance of adult neurogenesis is still unclear. Here, using a genetic

labeling method, we showed that in adult mice, continuous neurogenesis results in

replacement of the majority of granule neurons in the olfactory bulb and significant

addition of granule neurons to the hippocampal dentate gyrus. Strikingly, genetic

ablation of newly formed neurons in adult mice leads to gradual decrease of the

granule cell number in the olfactory bulb, inhibition of increases in the granule cell

number in the dentate gyrus, and impairment of behaviors in contextual and spatial

memory, which is known to be involved in hippocampus. These results suggest that

continuous neurogenesis is required for maintenance of the brain structures and

functions. For continuous neurogenesis, neural stem cells should be maintained in

the adult brain. We found that maintenance of neural stem cells in the adult brain

depends on the Notch effectorHes1 and its related genes, suggesting that Notch

signaling plays an important role in adult neurogenesis.

doi:10.1016/j.neures.2009.09.1490

SY1-B1-4 Epigenetic treatment for spinal cord injury

Kinichi Nakashima

Lab. Mol. Neurosci., Grad. Sch. Biol. Sci., Nara Inst. Sci. Tech., Japan

In the injured central nervous system (CNS), restoration of damaged neural net-

works is severely limited. Here, using a mouse model of spinal cord injury (SCI), we

show that transplanting neural stem cells (NSCs) and administering VPA to injured

mice synergistically enhances the functional recovery of their hindlimbs. Neuronal

butnot glial differentiation oftransplantedNSCswas promotedin VPA-treated mice.

Anterograde corticospinal tract tracing revealed that transplant-derived neuronspartiallyreconstructed the broken neuronalcircuits, most likely in a relay manner.

Ablationof the transplantedcells abolishedthe recoveryof hindlimbmotor function,

indicating that transplanted cells contributed directly to the improvement of motor

function. These data raise the possibility that epigenetic regulation in transplanted

neural stem cells can be exploited to provide treatment for SCI.

doi:10.1016/j.neures.2009.09.1491

SY1-B2-1 Imaging circuit assembly in the developing retina

Rachel Wong

University of Washington, USA

We are interested in pre- and postsynaptic interactions that shape the axonal and

dendritic architecture of retinal neurons, as well as their connectivity patterns.

Our investigations are based on wildtype and transgenic vertebrate models, using

a combination of live-cell imaging techniques and electrophysiology. I will focus

primarily on our recent findings on the role of neurotransmission in regulating neu-

ronal architecture as well as synapse development of inner retinal neurons in mice.

By perturbing excitatory transmissionin a subset of glutamatergicafferents, we dis-

covered that their target neurons show a reduced synapse density but surprisingly,

no alterations to dendritic structure. Likewise, axonal structure of presynaptic cells

with compromised transmission is similar to that of wildtype axons although their

presynaptic active zones had an abnormal substructure. Our current efforts are now

focused on simultaneous time-lapse imaging of pre- and postsynaptic structures to

gainmore insightinto thedynamicsof synapseassemblyin the transmission-altered

retinas.

doi:10.1016/j.neures.2009.09.1492

SY1-B2-2 Activity-dependent regulation of dendritic growth

Sayaka Takemoto-Kimura, Natsumi Ageta-Ishihara, Mio Nonaka,

Aki Adachi-Morishima, Kanzo Suzuki, Haruhiko Bito

Univ Tokyo Grad Sch Med, Tokyo, Japan

While it is believed that Ca2+ signalling plays important roles during early devel-

opment of neuronal circuits, the identity of the Ca2+ effectors pivotal to regulation

of cortical wiring has remained elusive. Here we present evidence indicating that

the CaMKK-CaMKI pathway critically regulates the morphogenesis of cortical neu-

rons. Distinct limbs of the CaMKKCaMKI cascade were specifically implicated in

determining the extent of either dendritic or axonal growth downstream of dif-

ferent growth/guidance signals. In particular, a lipid-raft-anchored CaM kinase,

CLICKIII/CaMKI, mediated BDNF-stimulated dendrite growth via Rac activation.Furthermore, we found that insertion of CLICK-III/CaMKI into dendritic rafts was

controlled by an activity-dependent palmitoylation process mediated by a Golgi-

localized palmitoyl acyl transferase GODZ. These lines of evidence point to the

crucial importance of targeted CaM kinase activation within discrete membrane

microdomains and cellular compartments in fine-tuning dendritic morphology dur-

ing neuronal development.

doi:10.1016/j.neures.2009.09.1493

SY1-B2-3 Mathematical modeling for self-organizing pattern of neu-

ronal dendrites

Atsushi Mochizuki 1, Kohei Shimono 2, Kaoru Sugimura3, Tadashi

Uemura 2

1 RIKEN ASI, Wako, Japan; 2 Grad Sch Biostd, Kyoto Univ, Kyoto, Japan;3 RIKEN BSI, Wako, Japan

Development of class-specific dendrites is a basis of the correct functioning of

nervous system. Tiling of dendritic arbors (complete, but minimum-overlapping

innervationof a field) supportsuniform reception ofinput stimuli.It hasbeen argued

that the underlying inhibitory interaction between dendrites is realized by contact-

dependent retraction and/or by repulsion of dendrites via extracellular suppressors.

In this study, we show that the development and regeneration of the tiling pattern

can be reproduced by 2 different mathematical models, in both of which dendrite

growth is coupled with dynamics of the extracellular suppressor that is secreted

from dendrites. The analysis of one model in three-dimensional space showed that

it generated patterns resemble phenotypes of the previously reported weak and

strong tiling mutants in vivo. The analysis of 2 models suggest that tiling patterns

can be achieved either by a local increase of the growth-promoting factor or by a

local decrease in production of the suppressor at branch ends.

doi:10.1016/j.neures.2009.09.1494

SY1-B2-4 Dendrite remodeling in adult Drosophila sensory neuronsKei-ichiro Yasunaga, Kazuo Emoto

Neural Morphogenesis Lab, National Institute of Genetics/JST PROTO,

Japan

During neuronalmaturation,dendrites developfrom immature neuritesinto mature

arbors. In response to changes in the environment, dendrites from certain mature

neurons can undergo large-scale morphologic remodeling. A group of Drosophila

peripheralsensory neurons,the class IV dendriticarborization (C4da)neurons, com-

pletely degrade and regrow their elaborate dendrites during pupal to adult stages.

We found that the regrowth process of the C4da dendrites is controlled by two

independent extrinsic mechanisms: The repulsive interactions between homophilic

branches establish entire dendritic fields, and the attractive interactions between

dendritic branches and muscle fibers determine precise positions of the individual

branches. These reveal that the Drosophila sensory neurons provide an excel-

lent system to dissect cellular and molecular mechanisms underlying the dendrite

remodeling in response to environmental changes. We isolated a couple candidate

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