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Cell Migration and Layer/Nuclear Formation

開催日 2014/9/11
時間 16:00 - 17:00
会場 Poster / Exhibition(Event Hall B)

PR domain protein Prdm8 knockout mouse exhibit abnormal development of upper layer neurons in the neocortex

  • P1-080
  • 岩井 亮太 / Ryota Iwai:1,2 井上 真悠子 / Mayuko Inoue:1 加藤 雅紀 / Masaki Kato :3 本田 文 / Aya Honda:1 手島 羽香 / Waka Teshima:1 渡部 千里 / Chisato Watanabe:1 眞貝 洋一 / Yoichi Shinkai:3 水谷 健一 / Ken-ichi Mizutani:1,4 
  • 1:同志社大学大学院 脳科学研究科 / Graduate School of Brain Science, Doshisha University 2:同志社大学 生命医科学部 / Fac Life Sci, Doshisha Univ, Kyoto, Japan 3:理化学研究所 / RIKEN, Saitama, Japan 4:科学技術振興機構 / JST, Tokyo, Japan 

During neocortical development, a multitude of cellular events must
all occur with exquisite spatiotemporal control. PRDM proto-
oncogene transcription factor family are new candidates implicated in
the control of the developing neocortex. This is because multiple genes
in the Prdm family are expressed in the developing mouse neocortex in a
spatially and temporally restricted manner, and our previous study has
shown that Prdm8 expression is specifically localized in the
intermediate zone at embryonic stage and the upper layer neocortex at
postnatal stage, respectively.
We established Prdm8 KO mice (Prdm8-/-) by the disruption of Prdm8
locus completely, and observed that weight loss of whole brain in the
Prdm8-/-, compared with WT. However, immunostaining data showed that the
number of progenitors and their ratio of proliferation were not
significantly different between WT and Prdm8-/- at embryonic stages. We
also confirmed that the expression of intermediate zone-specific
molecular markers such as NeuroD1 and Unc5d were not affected in the
Prdm8-/- neocortex. Therefore, we next focused on the analysis of the
postnatal neocortex by using the layer-specific molecular markers, which
include Ctip2, a marker for layer V neurons, Cux1, a marker for layer II
-IV neurons, and Brn2, a marker for layer II-III neurons. Interestingly,
we found that the expression pattern of upper-layer neuronal markers
such as Cux1 and Brn2, was significantly affected in Prdm8-/- neocortex,
although deep-layer neuronal markers were not different between WT and
KO mice.
Furthermore, the genomic binding sites of Prdm8 in the dorsal
telencephalon were mapped by chromatin immunoprecipitation followed by
high-throughput sequencing (ChIP-seq), and we identified 6,622 specific
Prdm8 binding sites, and found that some peaks contain upstream region
of layer specific marker genes, such as Cux1, Brn2, and Bhlhb5. These
results suggest that the Prdm8 is one of the important factors to
regulate the precise development or maturation of upper layer neurons.

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