When citing an abstract from the 2014 annual meeting please use

1862 Pages·2014·7.43 MB·English

by  Michele Appley

When citing an abstract from the 2014 annual meeting please use the format below.

[Authors]. [Abstract Title]. Program No. XXX.XX. 2014 Neuroscience Meeting Planner.
Washington, DC: Society for Neuroscience, 2014. Online.

2014 Copyright by the Society for Neuroscience all rights reserved. Permission to republish any
abstract or part of any abstract in any form must be obtained in writing by SfN office prior to
publication.
Poster
588. Neuronal Differentiation: Transcriptional Mechanisms
Location: Halls A-C
Time: Tuesday, November 18, 2014, 1:00 PM - 5:00 PM
Program#/Poster: 588.01/A1
Topic: A.02. Neurogenesis and Gliogenesis
Support: NIH Grant DC008955
Burke Medical Research Institute
Title: Differential conservation of transcription factor codes specifying mouse and human
olfactory bulb interneuron phenotypes
Authors: *N. FUJIWARA1, J. W. CAVE1,2;
1BURKE MEDICAL RESEARCH INSTITUTE, WHITE PLAINS, NY; 2WEILL CORNELL
MEDICAL COLLEGE, BRAIN AND MIND RESEARCH INSTITUTE, New York, NY
Abstracts: The mechanisms that generate neuronal phenotypic diversity in the mammalian brain
are not fully established. To better understand these mechanisms, this study examined
transcription factor specification of olfactory bulb interneuron phenotypes. Most studies
examining phenotypic diversity in olfactory bulb interneurons have been conducted with rodents
and have indicated that individual phenotypes are specified by combinatorial co-expression of
different transcription factors. To establish whether the transcription factor codes established in
the mouse are conserved in the human olfactory bulb, we examined adult human and mouse
olfactory bulb tissue by immunofluorescence. These studies compared the co-expression of
MEIS2, SP8, FOXP2 and PAX6 transcription factors in interneurons specified by the expression
of either Calretinin, Calbindin or Tyrosine Hydroxylase. In both species, FOXP2 and PAX6 were
co-expressed with Calbindin and Tyrosine Hydroxylase, respectively. MEIS2 was co-expressed
with both Calretinin and Tyrosine Hydroxylase in both species, but co-expression with Calbindin
was only observed in mice. SP8 was co-expressed with Calretinin in both species, but in humans,
it was also observed in cells containing either Calbindin or Tyrosine Hydroxylase. The co-
expression of SP8 with Calbindin in humans coincided with a co-expression of Calbindin and
Calretinin that was not observed in mice. The human-specific co-expression of Calbindin and
Calretinin revealed a novel olfactory bulb interneuron phenotype not observed in mice. Together,
the findings in this study show some significant differences in transcription factor co-expression
patterns in mouse and human olfactory bulb interneurons, which may underlie differential
phenotype specification between these species.
Disclosures: N. Fujiwara: None. J.W. Cave: None.
Poster
588. Neuronal Differentiation: Transcriptional Mechanisms
Location: Halls A-C
Time: Tuesday, November 18, 2014, 1:00 PM - 5:00 PM
Program#/Poster: 588.02/A2
Topic: A.02. Neurogenesis and Gliogenesis
Support: Jerome Lejeune Foundation
Title: Mechanisms of neuronal maturation are impaired in the developing neocortex of Mecp2
null embryos
Authors: *F. BEDOGNI1, C. COBOLLI GIGLI1, D. POZZI2, R. ROSSI3, L. SCARAMUZZA1,
C. ZELI1, C. KILSTRUP-NIELSEN4, M. MATTEOLI2, N. LANDSBERGER1;
1San Raffaele Res. Inst., Milan, Italy; 2Humanitas Clin. and Res. Ctr., Milan, Italy; 3Inst.
Nazionale Genetica Molecolare, Milan, Italy; 4Univ. of Insubria, Varese, Italy
Abstracts: Rett syndrome (RTT) is a neurological disorder that affects mainly girls (1/10.000
live born female) and is characterized by autistic features, seizures, ataxia and stereotypical hand
movements. Due to the timing of the onset of RTT symptoms (6-18 months of life), researchers
so far mainly studied the postnatal period. However, evidences of subtle defects at birth (both in
humans and RTT animal models) are now increasing, while the investigation of any possible
prenatal neurodevelopment impairments has been largely neglected. We thus hypothesized that
MeCP2 (the cause of roughly 90% of RTT cases worldwide) could play a role during embryonic
and early postnatal development, as we detected Mecp2 expression in both progenitors and post-
mitotic neurons of the cerebral cortex as early as E10. Searching for possible transcriptional
impairments, possibly leading to subtle alterations during early stages of development, we
performed a microarray analysis on wt and Mecp2 null embryonic cortical tissues (E15). Overall,
our transcriptional screening highlighted the deregulation of a large plethora of genes typically
expressed by maturing or matured neurons. This is suggestive of a delay (or possibly a stall) in
the acquisition of the full mature neuronal identity, as many of these genes were accordingly
deregulated at later time points (E18 and P8). Of particular interest for their involvement in
activity dependent maturation, we detected defects in the transcription of several receptors and
ionic channels that likely produced perturbation in down stream signalling pathways, as verified
with functional experiments. Our data suggest the intriguing hypothesis that impairments during
early embryonic maturation of the Mecp2 null cortex can lead to subtle pre-symptomatic features
and concur to the typical neuronal impairments in adulthood, thus opening up new perspectives
on the aetiology of RTT neurological features.
Disclosures: F. Bedogni: None. C. Cobolli Gigli: None. D. Pozzi: None. R. Rossi: None. L.
Scaramuzza: None. C. Kilstrup-Nielsen: None. M. Matteoli: None. N. Landsberger:
None. C. Zeli: None.

Poster
588. Neuronal Differentiation: Transcriptional Mechanisms
Location: Halls A-C
Time: Tuesday, November 18, 2014, 1:00 PM - 5:00 PM
Program#/Poster: 588.03/A3
Topic: A.02. Neurogenesis and Gliogenesis
Support: NEI P30 EY022589
NEI P30 EY014081
Research to Prevent Blindness
Title: Novel regulatory mechanisms for the SoxC transcriptional network required for visual
pathway development
Authors: *X. ZHANG1, J. HERTZ2, X.-L. JIN2, B. A. DEROSA2, J. Y. LI2, P.
VENUGOPALAN1, D. A. VALENZUELA2, R. D. PATEL2, K. R. RUSSANO1, S. A.
ALSHAMEKH2, D. VELMESHEV3, Y. CHENG2, T. M. BOYCE2, A. DREYFUSS2, M. S.
UDDIN2, K. J. MULLER4, D. M. DYKXHOORN3, J. L. GOLDBERG1;
1Shiley Eye Ctr., UCSD, La Jolla, CA; 2Bascom Palmer Eye Institute, Interdisciplinary Stem
Cell Inst., 3Hussman Inst. for Human Genomics, 4Dept. of Physiol. and Biophysics, Univ. of
Miami, Miami, FL
Abstracts: What pathways specify retinal ganglion cell (RGC) fate in the developing retina?
Here we report on mechanisms by which a new molecular pathway involving Sox4/Sox11
required for RGC differentiation from retinal progenitor cells (RPCs) and for optic nerve
formation in mice in vivo, and sufficient to differentiate human induced pluripotent stem cells
into electrophysiologically active RGC-like cells. We show a regulatory network where by the
previously described inhibitor of RGC differentiation, REST, depends on suppression of Sox4
expression, and provide evidence for a novel soluble regulator for RGC differentiation, TGFβ
superfamily member GDF-15, which also acts through Sox4 to induce RGC differentiation from
progenitor cells. Although our data suggests that Sox4 and Sox11 are independently required for
RGC development, the two family members interact such that the normal SUMOylation of
Sox11, which decreases its nuclear localization and suppresses its pro-RGC activity, is decreased
in the absence of Sox4, allowing Sox11 to compensate for Sox4 absence. These data define
novel regulatory mechanisms for this SoxC molecular network, and suggest pro-RGC molecular
manipulations with potential promise for cell replacement-based therapies for glaucoma and
other optic neuropathies.
Disclosures: X. Zhang: None. J. Hertz: None. X. Jin: None. B.A. Derosa: None. J.Y. Li:
None. P. Venugopalan: None. D.A. Valenzuela: None. R.D. Patel: None. K.R. Russano:
None. S.A. Alshamekh: None. D. Velmeshev: None. Y. Cheng: None. T.M. Boyce: None. A.
Dreyfuss: None. M.S. Uddin: None. K.J. Muller: None. D.M. Dykxhoorn: None. J.L.
Goldberg: None.

Poster
588. Neuronal Differentiation: Transcriptional Mechanisms
Location: Halls A-C
Time: Tuesday, November 18, 2014, 1:00 PM - 5:00 PM
Program#/Poster: 588.04/A4
Topic: A.02. Neurogenesis and Gliogenesis
Support: EU ZF-HEALTH 242048
EU DOPAMINET
EU mesDAneurodev
DFG SFB 780-B6
Title: Genetic control of dopaminergic neuron subtype differentiation in zebrafish
Authors: *W. DRIEVER, M. MANOLI, M. RATH, E. CARL, T. MUELLER, A. FILIPPI;
Univ. Freiburg, Freiburg, BW 79104, Germany
Abstracts: Distinct groups of dopaminergic neurons develop at defined anatomical sites in the
brain to modulate function of a large diversity of local and far-ranging circuits involved in motor
control, perception, sleep and the regulation of emotion-related behavior. We use zebrafish
embryos as genetic models to understand how transcriptional regulatory networks control
dopaminergic subtype identity, co-transmitter phenotypes and projection behavior. Zebrafish
embryos develop dopaminergic neurons at anatomical sites similar to mammals, except for the
lack of a mesencephalic dopaminergic group. We have mapped the complete projectome of all
dopaminergic groups in zebrafish, and have also characterized gabaergic and glutamatergic co-
transmitter phenotypes for each dopaminergic subtype. The only dopaminergic neurons in
zebrafish to provide ascending projections into the subpallium/striatum are A11-type posterior
tubercular dopaminergic neurons which depend on the Orthopedia transcription factor for their
development. these neurons share glutamatergic co-transmission with the mammalian ascending
systems. Zebrafish develop an endostriatal dopaminergic system, which provided most of the
dopaminergic arborization within the striatum. this striatal system is characterized by gabaergic
cotransmission, providing dopaminergic activity with two distinct co-transmitter phenotypes to
the striatum. We have systematically mapped transcription factor expression to each of the
anatomical dopaminergic groups in zebrafish to define their transcriptional codes, and use
genetic loss- and gain-of-function approaches to functionally dissect the transcriptional networks
controlling dopaminergic subtype specificity. Our data suggest specific combinations of
patterning, neurogenesis and differentiation transcription factors to drive dopamine subtype
specification, co-transmitter phenotypes and projection behavior.
Disclosures: W. Driever: None. M. Manoli: None. M. Rath: None. E. Carl: None. T.
Mueller: None. A. Filippi: None.

Poster
588. Neuronal Differentiation: Transcriptional Mechanisms
Location: Halls A-C
Time: Tuesday, November 18, 2014, 1:00 PM - 5:00 PM
Program#/Poster: 588.05/A5
Topic: A.02. Neurogenesis and Gliogenesis
Support: Medical Research Council
Title: The significance of NeuroD1 for external germinal layer formation
Authors: M. HANZEL1, T. BUTTS1, *R. J. WINGATE2;
1MRC Ctr. for Developmental Neurobio., 2MRC Ctr. Dev Neurobiol, King's Col. London,
London, United Kingdom
Abstracts: The cerebellum has evolved elaborate foliation in the amniote lineage as a
consequence of extensive transit amplification in a transient external germinal layer (EGL)
mediated by the bHLH transcription factor, Atonal 1 (Atoh1). At the end of transit amplification,
granule cell precursors (GCPs) transition into mature neurons having undergone a massive
expansion in number. Differentiation is associated with the down regulation of Atoh1 and
upregulation of NeuroD1. To explore the characteristics of transit amplifying cells, we have
examined cerebellar development in the embryonic chicken, mouse and Xenopus.
Electroporation of conditional reporters in vivo in chick at E6-E8 and in cerebellar slice of both
chick and mouse cultured at E10-14 and P1-5, respectively, has allowed us to directly observe
individual granule cells from their origins at the rhombic lip to their descent into the internal
granular layer (IGL) and explore the relationship between NeuroD1 and Atoh1. Our assay
employs two bHLH transcription factor enhancer constructs: NeuroD1::GFP and Atoh1::Cre-
recombinase. By titrating the concentration of this cre-recombinase with co-electroporated “lox-
stop-lox” plasmids encoding either GFP or mCherry, we label progressively sparser cells. Using
this strategy, we show that Atoh1 is expressed in granule cell precursors displaying a variety of
different morphological characteristics. By contrast, the NeuroD1 enhancer construct labels
GCPs as they leave the cell cycle and initiate an inward radial migration suggesting a key role
for NeuroD1 in differentiation. To investigate this, we overexpressed full-length NeuroD1 within
the chick GCP population and assessed the consequences for granule cell development. When
expressed in early rhombic lip migrants (E5), NeuroD1 upregulation cell autonomously inhibits
the formation of EGL cells. When expressed in GCPs of the EGL, NeuroD1 cell autonomously
terminates proliferation, triggers radial migration and down regulates Atoh1. NeuroD1 is thus
sufficient to trigger exit from the EGL. Intriguingly this regulatory relationship appears to be a
relatively recent amniote innovation. In the frog (an anamniote), which has a simple unfoliated
cerebellum, NeuroD1 and Atoh1 are co-expressed in a transient granule cell layer that forms on
the surface of the cerebellum at metamorphosis. This external layer is nevertheless non-
proliferative and thus does not comprise an external germinal layer. The evolution of transit
amplification in the EGL thus required adaptation of NeuroD1, both in the timing of its
expression and regulatory function, with respect to Atoh1 in amniotes.
Disclosures: M. Hanzel: None. T. Butts: None. R.J. Wingate: None.

Poster
588. Neuronal Differentiation: Transcriptional Mechanisms
Location: Halls A-C
Time: Tuesday, November 18, 2014, 1:00 PM - 5:00 PM
Program#/Poster: 588.06/A6
Topic: A.02. Neurogenesis and Gliogenesis
Title: Analyzing the role of FoxD4 in neuronal differentiation using a mouse embryonic stem
cell model
Authors: *J. H. SHERMAN1, B. KARPINSKI-OAKLEY2, M. FRALISH1, S. MOODY1, A.
LAMANTIA1, T. MAYNARD1;
1The George Washington Univ., Washington, DC; 2The, Washington, DC
Abstracts: Foxd4 is a forkhead box family transcription factor. In Xenopus embryos, foxD4/5
serves as a master regulator of numerous neural transcription factors and plays a key role in
directing embryonic stem cells towards a neural stem cell (NSC) lineage. The homologous gene
in mice, FoxD4, is expressed in the embryonic central nervous system in a pattern similar to
Xenopus. Our data indicates that this transcription factor may play similar role in promoting the
development of mammalian NSCs. We used mouse embryonic stem cells (mESCs) to assess the
NSC-promoting activity of Foxd4. A stable mESC line expressin a Foxd4 targeted siRNA was
used to reduce Foxd4 expression in mESCs in a LIF/RA dependent NSC differentiation assay.
Our results show clearly that this loss of Foxd4 function diminishes the capacity of mESCs to
respond to the NSC-promoting environment in the LIF/RA NSC differentiation assay. We also
found that Foxd4 knockdown does not affect mESCs pluripotency. Furthermore, FoxD4
knockdown results in decreased levels of neural differentiation markers, high levels of
undifferentiated cell markers and lack of expression of mature neuronal markers. In addition, a
mESC line was generated that over-expresses FoxD4 to assess the consequences of gain of
function. We found that FoxD4 upregulation results in low levels of undifferentiated neuronal
markers with increased expression of markers for neuronal maturation and differentiation. We
also confirmed that Foxd4 (the murine gene) has similar functions to its Xenopus counterpart by
injecting full length Foxd4 into frog oocytes and assessing its effects on neural induction. As is
the case for foxD4/5, murine Foxd4 accelerates and enhances expression of neuronal precursor
and differentiation marker. Finally, localization analysis indicates that Foxd4 is expressed in the
neural tube and olfactory placode epithelium at midgestation. We are currently using siRNA
electroporation in an olfactory placode explant assay to assess the function of Foxd4 in
developing embryonic neurogenic ectoderm. Together, our results show that Foxd4, like its
Xenopus orthologue, is a key regulator of the transition from embryonic stem cell to committed
neurogenic neural stem cell.
Disclosures: J.H. Sherman: None. M. Fralish: None. B. Karpinski-Oakley: None. T.
Maynard: None. S. Moody: None. A. LaMantia: None.

Poster
588. Neuronal Differentiation: Transcriptional Mechanisms
Location: Halls A-C
Time: Tuesday, November 18, 2014, 1:00 PM - 5:00 PM
Program#/Poster: 588.07/A7
Topic: A.02. Neurogenesis and Gliogenesis
Support: R01 DK064678/DK/NIDDK NIH HHS/United States
R01 NS054941/NS/NINDS NIH HHS/United States
Title: Stat3 promotes motor neuron differentiation by collaborating with motor neuron-specific
LIM complex
Authors: S. SEO1, *J. C. RHEE2, S. LEE1, R. SHEN3, H. CHO3, J. LEE3, S. LEE3;
1Seoul Natl. Univ., Seoul, Korea, Republic of; 2Dept. of Pharmacol., SNU Pharm., Seoul, Korea,
Republic of; 3OHSU, Portland, OR
Abstracts: The motor neuron (MN)-hexamer complex consisting of LIM homeobox 3, Islet-1,
and nuclear LIM interactor is a key determinant of motor neuron specification and
differentiation. To gain insights into the transcriptional network in motor neuron development,
we performed a genome-wide ChIP-sequencing analysis and found that the MN-hexamer
directly regulates a wide array of motor neuron genes by binding to the HxRE (hexamer response
element) shared among the target genes. Interestingly, STAT3-binding motif is highly enriched
in the MN-hexamer-bound peaks in addition to the HxRE. We also found that a transcriptionally
active form of STAT3 is expressed in embryonic motor neurons and that STAT3 associates with
the MN-hexamer, enhancing the transcriptional activity of the MN-hexamer in an upstream
signal-dependent manner. Correspondingly, STAT3 was needed for motor neuron differentiation
in the developing spinal cord. Together, our studies uncover crucial gene regulatory mechanisms
that couple MN-hexamer and STAT-activating extracellular signals to promote motor neuron
differentiation in vertebrate spinal cord.
Disclosures: S. Seo: None. J.C. Rhee: None. S. Lee: None. R. Shen: None. H. Cho: None. J.
Lee: None. S. Lee: None.

Poster
588. Neuronal Differentiation: Transcriptional Mechanisms
Location: Halls A-C
Time: Tuesday, November 18, 2014, 1:00 PM - 5:00 PM
Program#/Poster: 588.08/A8
Topic: A.02. Neurogenesis and Gliogenesis
Support: JSPS KAKENHI 24300116
JSPS KAKENHI 23700410
MEXT KAKENHI 25123701
Title: Postmitotic dorsal spinal cord neurons are transfated into commissural neurons by induced
misexpression of Barh1
Authors: *T. SATO1,2, Y. MUROYAMA3, T. SAITO3;
1Dev. Neurosci. Grad. Sch. of Med. Tohoku Univ., Sendai, Japan; 2Current Address: Dev.
Neurosci., Grad. Sch. of Med., Tohoku Univ., Sendai, Japan; 3Dept. of Dev. Biol., Grad. Sch. of
Med., Chiba Univ., Chiba, Japan
Abstracts: Mammalian Barh1 (Mbh1), which is a Bar-class homeobox gene, has been shown to
confer commissural neuron identity on dorsal cells in the mouse embryonic spinal cord. In our
previous experiments, Mbh1 was transfected into neural stem/progenitor cells and misexpressed
in both neural stem/progenitor cells and postmitotic neurons using in vivo electroporation and a
ubiquitous CAG promoter vector. It has not been clear whether Mbh1 functions in neural
stem/progenitor cells or postmitotic neurons during the fate change into commissural neurons.
We have recently established a gene induction method by combining in vivo electroporation with
the newest version of the Tet-On system. This method enables efficient and strict induction of
gene expression in targeted postmitotic neurons in the presence of doxycycline (Dox). In the
absence of Dox, leaky expression occurrs only at extremely low levels. We have applied the
method to the developing mouse spinal cord to determine whether postmitotic cells would be
transfated into commissural neurons by Mbh1. After in vivo electroporation, postmitotic cells
that were highly labeled with BrdU, six hours before the induction of Mbh1, became neurons
positive for Dcc, which is a netrin receptor and a marker of commissural neurons in the
developing spinal cord, mimicking the phenotype of Mbh1 misexpression under the control of
the CAG promoter. This finding suggests that even postmitotic neurons are transfated into
commissural neurons by Mbh1. This work was supported by JSPS KAKENHI grant numbers
24300116 (to Saito) and 23700410 (to Sato) and MEXT KAKENHI grant number 25123701 (to
Saito).
Disclosures: T. Sato: None. Y. Muroyama: None. T. Saito: None.

Poster
588. Neuronal Differentiation: Transcriptional Mechanisms
Location: Halls A-C