Al Diri, Issam

Vetter, Monica L.

Elsevier - Publisher Connector 

The vertebrate telencephalon has the most complex region of the
nervous systemand is responsible for the highest level of neural function,
such as learning, memory, consciousness, emotion and so on. To analyze
the complicated function of the telencephalon, one of the important
issues is that how the neural cell fate is determined during development.
However, the molecular mechanisms of neural cell fate determination
have not been fully elucidated. To make clear these molecular mechan-
isms,wehave takena forwardgenetics approach inzebrafish.We isolated
anovel zebrafishmutantkuririn (krr) and found that krrgene is expressed
in the dorsal telencephalon, ventral diencephalon, and olfactory placode.
In consequenceof thephenotypic analyses of krrmutant,we showed that
the number of GABAergic neurons is increased instead of the glutama-
tergic neurons in the telencephalon. Since this phenotype of krrmutant is
very similar to that of Neurogenin1 (Ngn1); Neurogenin2 (Ngn2) double
mutant inmouse,we examined the expression ofngn1 in krrmutant, and
found that its expression is reduced in the dorsal telencephalon. It is well
knownthatngns arenegatively regulatedby the transcription factorHes1.
We next examined the expression of Hes1-related gene, her6 in krr
mutant, and confirmed that this expression is expanded in the dorsal
telencephalon. Together, we propose that Krr regulates ngn1 through the
regulation of her6 gene in the telencephalon.
doi:10.1016/j.ydbio.2010.05.300
Program/Abstract # 292
Six1 is indispensable for production of functional apical and basal
progenitors during olfactory epithelial development
Keiko Ikedaa, Ryoichiro Kageyamab, Kiyoshi Kawakamia
aDiv. of Biol., Jichi Med. Univ., Tochigi, Japan
bInst for Virus Res., Kyoto Univ., Kyoto, Japan
The olfactory epithelium (OE) is a good model system for studying
principles of stem/progenitor cell biology, because of its capacity for
continuous neurogenesis throughout life. The developmentofmouseOE
is divided into two stages, early and established neurogenesis. We
previously reported that Six1 is essential for production of pioneer
neurons in the early neurogenesis that occurs at embryonic day (E) 10.0.
Here, we focused on the role of Six1 in the established neurogenesis. In
the established neurogenesis, which starts at E12.5, sustentacular cells
and olfactory receptor neurons (ORNs) are produced from apical and
basal progenitors, respectively. We found that Six1 is expressed in both
apical and basal progenitors. In Six1−/−, apical proliferating cells were
absent and no morphologically identifiable sustentacular cells were
observed. Consistently, the expression of Notch2 and Jagged1 in the
apical layerwas absent in Six1−/−. On the other hand, basal proliferating
cells were observed in Six1−/−, but the expression of Ngn1, NeuroD,
Notch1, and Jagged2 in the basal layer was absent in Six1−/−. The
expression of Mash1, the determination gene for ORNs, and Hes genes
was enhanced in Six1−/−. As a result, Six1−/− showed lack of mature
ORN throughout development and disorganization of OE after E12.5.We
conclude that Six1 regulates production of functional apical and basal
progenitors in the established neurogenesis during OE development
through regulating various genes such as neuronal basic helix–loop–
helix and genes involved in Notch signaling pathway.
doi:10.1016/j.ydbio.2010.05.301
Program/Abstract # 293
Sensory neuron differentiation is regulated by Notch signaling in
the trigeminal placode
Rhonda N.T. Lassiter, Matthew K. Ball, Jason S. Adams, Brian T. Wright,
Michael R. Stark
Physiology and Developmental Biology, BYU, Provo, UT, USA
Trigeminal sensory neurons develop from the neural crest and
neurogenic placodes, and have been studied as a principle model of
sensory neuron formation. While the Notch pathway has been
extensively characterized in central nervous system development
and other developmental processes, it has not been well character-
ized in sensory neurogenesis. Here we studied the functional role of
Notch signaling in the ophthalmic placode, a prime model of sensory
neurogenesis. To establish a good spatiotemporal description of
Notch pathway genes in the chick trigeminal placode, a stage-specific
expression analysis was conducted, showing that expression of most
Notch pathway genes and effectors are expressed in the placode, with
expression primarily being confined to ectodermal cells. Expression
was highest at stages of peak neuronal differentiation. To test the
function of Notch signaling in opV placode differentiation, Notch was
blocked using DAPT, or signaling was activated by misexpression of
the Notch intracellular domain. Notch activation resulted in a
significant reduction in sensory neurogenesis. Cells remained in the
ectoderm and did not differentiate ectopically. DAPT exposure re-
sulted in a dramatic increase in neurogenesis without increasing
proliferation, where many differentiated cells were found in the
mesenchyme and, surprisingly, within the ectoderm. This is the first
result clearly showing ectopic neurogenesis in the trigeminal
placodes after experimental manipulation of a molecular signaling
pathway, thus identifying Notch signaling as a primary regulator of
the sensory neuron fate in the opV placode.
doi:10.1016/j.ydbio.2010.05.302
Program/Abstract # 294
The polycomb repressive complex PRC2 regulates retinal
differentiation in Xenopus
Issam Al Diri, Monica L. Vetter
Department of Neurobiology and Anatomy, University of Utah,
Salt Lake City, UT, USA
The mechanisms that govern the transition of retinal progenitors
from proliferation to differentiation are not fully understood. Recent
studies have established that the chromatin remodeling complex
PRC2 is a key switch required for dividing cells to execute correct
genetic reprogramming as they exit the cell cycle and undergo
differentiation in a variety of biological contexts, including in
embryonic stem cells and during cortex development. PRC2 represses
genes by trimethylating lysine 27 of histone 3 tail (H3K27 me3), a
histone mark that is associated with chromatin compaction. Here we
report the involvement of PRC2 in regulating the transition from
retinal proliferation to differentiation during eye development. We
show that the transcripts of the core subunits of PRC2 are
coincidently expressed in retinal progenitors and are downregulated
upon retinal differentiation. Surprisingly, we found that H3K27me3
levels greatly increase in terminally differentiated cells. Inhibition of
Xez, the catalytic subunit of PRC2, using a translation blocking
morpholino leads to a marked decrease in H3K27me3 levels in retinal
cell types. Blocking Xez causes a reduction in eye size and inhibition
of differentiation genes. Importantly, targeted knockdown of Xez in
retinal progenitors biases cell fate toward late born cell types,
suggesting that retinal differentiation is delayed or inhibited. Our
data establishes PRC2 as a major player in retinal neurogenesis and
suggests that it may have multiple roles in eye development,
including regulation of retinal proliferation and/or differentiation.
This work was supported by NIH grant# EY012274 to MLV.
doi:10.1016/j.ydbio.2010.05.303
498 Abstracts


The polycomb repressive complex PRC2 regulates retinal differentiation in Xenopus 

file:///data/remote/core/dit/data/elsevier/pdf/619/aHR0cDovL2FwaS5lbHNldmllci5jb20vY29udGVudC9hcnRpY2xlL3BpaS9zMDAxMjE2MDYxMDAwNTg5MA==.pdf

The polycomb repressive complex PRC2 regulates retinal differentiation in Xenopus

Abstract

Similar works

Full text

Available Versions

Elsevier - Publisher Connector

Elsevier - Publisher Connector