Klassen, Matthew P.

Poon, Vivian Y.

Shen, Kang

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involved, including members of the FGF, ephs, semaphorin, netrin and
slit families. Hypothyroid mice appear to have fewer afferent and
efferent ﬁbers extending to inner and outer sensory hair cells and
fewer synapses with these cells. Moreover, thyroid hormone regulates
cochlear expression of genes encoding putative axon guidance cues.
The severity of hearing loss is dependent upon the genetic background
strain and can be completely rescued by a locus on chromosome 2.
Discovery of the identity of such a protective factor could lead to
developing treatments that would enhance axonal outgrowth neces-
sary for regenerative therapy in common age-related or environmen-
tally-induced hearing loss, and for the rare cases of congenital
hypothyroidism-induced deafness that are not responsive to thyroid
hormone supplementation. (March of Dimes)
doi:10.1016/j.ydbio.2008.05.016
Program/Abstract # 12
The role of Hox genes in the speciﬁcation of neural crest
Stephanie R. Kadison a, Toshi Iwashita b, Sean J. Morrison b,
Catherine E. Krull a
a Biological and Material Sciences, University of Michigan, Ann Arbor, MI,
USA
b
Stem Cell Biology, HHMI/LSI, University of Michigan, Ann Arbor, MI, USA
The neural crest (NC) is a cell population derived from the dorsal
neural tube that gives rise to distinct cell types during embryonic
development. Depending upon their anterior–posterior (A/P) level, NC
generate cells as disparate as neurons and cartilage. The currentmodel
for NC speciﬁcation suggests that NC fate (with the exception of
melanocytes) is determined by environmental cues they encounter
during migration, rather than by intrinsic cues prior to leaving the
neural tube. To test this model, we performed microarray analyses on
post-migratory NC from two distinct cell/tissue types: enteric neurons
and sciatic nerve. Notably, we found that Hox genes are differentially
expressed between these populations. While it is known that Hox
genes play a role in the generation of cephalic NC-derived-structures,
little is known about their function in NC derived from other regions of
the neural tube. To test whether Hox genes represent an intrinsic cue
sufﬁcient to drive NC fate, we misexpressed posteriorly-expressed
Hoxb7 in anterior, occipital NC using in ovo electroporation. At levels
inconsistent with dorsal root ganglia (DRG) growth, we observed the
formation of ectopic DRG, determined by Islet1/2 and Brn3a
immunoreactivity, suggesting that Hoxb7 confers a truncal identity
to occipital NC. Similar results are observed when other paralogous
Hox genes are misexpressed. Collectively, these results provide
support for an intrinsic model of NC fate speciﬁcation. Additional
experiments are currently underway which will verify whether Hox
genes are required to specify diverse populations of NC.
doi:10.1016/j.ydbio.2008.05.017
Program/Abstract # 13
Extrinsic mechanisms regulate synapse formation
Kang Shen, Vivian Y. Poon, Matthew P. Klassen
Department of Biology, Neuroscience Program, Stanford University,
Stanford, CA 94305, USA
Polarity is an essential feature of many cell types, including
neurons, the primary building blocks of the brain. These highly
polarized cells integrate information from local inputs through their
dendrites and propagate nerve impulses to distant targets through a
single axon. The formation of this polarized structure can be
subdivided into at least two stages: the initial establishment of
axons and dendrites, followed by the polarized localization of axonal
and dendritic cargo. While intrinsic factors have been shown to
regulate the polarized localization of axonal proteins, extracellular
cues that coordinate neuronal polarity in vivo have not been explored.
Here, we show that axon guidance cue UNC-6/netrin and its receptor
UNC-5 exclude presynaptic components from the dendrite of the C.
elegansmotor neuronDA9which normally reside in a regionwith high
UNC-6 concentration. In unc-6 and unc-5 mutants, synaptic vesicles
and active zone proteins are mislocalized to the DA9 dendrite. In
addition, ectopically expressed UNC-6/netrin, acting through UNC-5,
is sufﬁcient to exclude endogenous synapses from nearby DA9 axon.
Interestingly, the antisynaptogenic activity of UNC-6/netrin is inter-
changeable with that of LIN-44/Wnt despite the different receptors
utilized, suggesting that extracellular cues such as Netrin and Wnts
not only guide axon navigation but also regulate the polarized
accumulation of presynaptic components through local exclusion.
doi:10.1016/j.ydbio.2008.05.018
Program/Abstract # 14
Neuromancer-1 and neuromancer-2 regulate cell fate speciﬁcation
in the embryonic CNS of Drosophila melanogaster
Sandra M. Leal a, Li Qian c, Rolf Bodmer d, James B. Skeath b
a Department of Biological Sciences, University of Southern MS,
Hattiesburg, MS, USA
b Department of Genetics, Washington University Medical School,
St. Louis, MO, USA
c The Gladstone Institute, San Francisco, CA, USA
d The Burnham Institute, La Jolla, CA, USA
T-box genes encode a family of transcription factors that regulate a
broad range of developmental processes in vertebrates and inverte-
brates. In addition to their roles in regulating heart and epidermal
development in Drosophila, we provide evidence that the T-box genes
neuromancer-1 (nmr-1) and neuromancer-2 (nmr-2) play key roles in
embryonic CNS development. We ﬁnd that nmr-1 and nmr-2 function
in a partially redundant manner to regulate neuronal cell fate by
inhibiting even-skipped (eve) expression in speciﬁc post-mitotic
neurons in the CNS. Consistent with these observations, we ﬁnd that
Nmr-1 and Nmr-2 transcription factor proteins also exhibit over-
lapping yet distinct expression proﬁles within the CNS. Nmr-2 is
expressed early in segment polarity stripes (Stage 9), deﬁned subsets
of neuroblasts, ganglion mother cells, and discrete sets of post-mitotic
neurons. In contrast, Nmr-1 expression is expressed much later
(Stages 11/12) and restricted to speciﬁc subsets of Nmr-2-expressing
post-mitotic neurons. Expression studies identify all Nmr-1- and Nmr-
2-positive neurons as interneurons and lineage studies map speciﬁc
sets of these neurons to neuroblast lineages 2-2, 6-1 and 6-2. Finally,
genetic analyses reveal that nmr-2 collaborates with nkx6 to regulate
eve expression in speciﬁc neurons. Thus, nmr-1 and nmr-2 appear to
be members of the eve transcriptional regulatory hierarchy that
speciﬁes neuronal subtype identities in the developing CNS.
doi:10.1016/j.ydbio.2008.05.019
Program/Abstract # 15
The zebraﬁsh unplugged/MuSK receptor controls pre- and
postsynaptic development
Michael Granato
Department of Cell and Developmental Biology, UPENN, Philadelphia, USA
467ABSTRACTS / Developmental Biology 319 (2008) 466–468


Extrinsic mechanisms regulate synapse formation 

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Extrinsic mechanisms regulate synapse formation

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