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Cell Migration and Layer/Nuclear Formation

開催日 2014/9/12
時間 11:00 - 12:00
会場 Poster / Exhibition(Event Hall B)

ATF5 is involved in development of the cerebral cortex

  • P2-091
  • 田辺 涼子 / Ryoko Tanabe:1 梅村 真理子 / Mariko Umemura:1 中野 春男 / Haruo Nakano:1 高橋 滋 / Shigeru Takahashi:1 高橋 勇二 / Yuji Takahashi:1 
  • 1:東薬大・生命科学・環境応用動物 / Sch of Life Sci, Tokyo Univ of Pharm & Life Sci, Tokyo, Japan 

Activating transcription factor 5 (ATF5), a member of the CREB/ATF family of transcription factors, is reported to regulate cell differentiation, survival and apoptosis. Recently, we have demonstrated that ATF5 expression is up-regulated at the translational step when cells respond to stress, including amino acid limitation, arsenite exposure, endoplasmic reticulum (ER) stress and heat shock. To examine the physiological role of ATF5 in vivo, we generated ATF5-dificient (ATF5-/-) mice by homologous recombination. As a result, the survival rate of ATF5-/- mice was decreased to around 30% by three days after birth.
It is reported that ATF5 is widely expressed in the brain and in the olfactory epithelium. Especially, ATF5 is highly expressed in the ventricular zone (VZ) and in the subventricular zone (SVZ) where neurogenesis occurs. We predicted that ATF5 is involved in development for cerebral cortex.
Mammalian cerebral cortex has a six-layered structure that is formed in a birth-date-dependent "inside-out" manner whereby the deepest layers form first and the most superficial layers form last.
In this study, to examine the relationship between ATF5 and cerebral cortex development, we analyzed the cortex layer by immunohistology using antibodies against Cux1 (marker of layer II-IV) and Ctip2 (marker of layer V&VI). Cux1-labeled cells are positioned in deeper cortical layers in ATF5-/- mice compared to wild type littermates. However, Ctip2-labeled cells are positioned in cortical layers V&VI and there is no difference between ATF5-/- mice and wild type littermates. These results suggest that localization of layer II-IV in ATF5-/- mice is disrupted and ATF5 is involved in migration of neuron of layer II-IV.
On the other hand, it has been reported that there are imbalance in inhibitory neuron and excitatory neuron in psychiatric disorder. To test this, we analyzed in inhibitory neuron by immunohistology using antibodies against GABA (marker of inhibitory neuron). The number of GABA-labeled cells was decreased in ATF5-/- mice compared to wild type littermates. These results indicated that ATF5 is involved in cerebral cortex development.

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