||Sayako Katada, Mizuki Honda, Jun Takouda, Katsuhide Igarashi, and Kinichi Nakashima, Developmental stage-dependent change of SMAD target genes defines the direction of neural stem cell differentiation induced by bone morphogenetic proteins, EMBO Conference Gene regulatory mechanisms in neural fate decision, 2007.09.
||Sayako Katada, Developmental stage-dependent change of SMAD target genes defines the neural stem cell fate, NCU Global Young Investigator forum, 2018.03.
||Sayako Katada, Implication of structure and functional changes of aging choroid plexus in neural stem cells regulation and brain functions, 2017.01.
||Choroid Plexus as the key regulator for development, maturation, and aging of the central nervous system.
||Sayako Katada, Mizuki Honda, Kinichi Nakashima, Oxygen regulates fate specification of neural stem cell during cortical development, Keystone Symposia:, 2015.02.
||堅田 明子, Impact of oxygen levels on fate switching of neural stem cell during corticogenesis, Neuro 2013, 2013.06, Oxygen (O2) is a substrate for energy production and deeply involved in the regulations of cellular metabolism. Although standard cell culture systems are exposed to the environmental O2 level of 21% (normoxia), actual O2 concentration in both developing and adult brains is 1-8% (hypoxia). Accumulating studies have revealed that O2 and its signal transduction pathways control cell proliferation, differentiation, and morphogenesis during the development of various tissues. The mammalian brain cortex comprises deep- and upper-layer neurons (layer V-VI and II-IV, respectively) and glial cells including astrocytes. All these cells are sequentially generated from common multipotent neural stem cells (NSCs) in this order during development. Therefore, NSCs at midgestation produce neither upper-layer neuron nor astrocyte, but mainly differentiate into deep-layer neurons. In addition, it is generally known that this NSC’s property change can be recapitulated in the embryonic stem (ES) cell culture systems. Recently, we have shown that the acquisition of astrogenic potential by NSCs is delayed in standard in vitro culture compared to those in vivo, while, in vitro culture under hypoxic condition can restore this impairment. Herein, we further analyze the impact of O2 levels during corticogenesis, i.e. deep- and upper-layer neuron production of NSCs. Mouse ES cells were cultured and induced to neural differentiation under normoxic or hypoxic condition, and the differentiation was evaluated by quantitative PCR and immunocytochemistry. We found that the expression of upper-layer specific neuronal genes in hypoxia culture appeared earlier than that in normoxia. Thus, it is conceivable that O2 levels contribute to appropriate scheduling of not only neuron-glia fate switching but also neuronal subtype specification throughout development..