title: Knockdown of FoxO3a induces increased neuronal apoptosis during embryonic development in zebrafish.
abstract: Neuronal apoptosis sculpts the developing brain, and nearly all identified classes of neurons seem to be produced "in excess" during development. FoxO transcription factors regulate apoptosis in vitro in deprived of neurotrophins. It is unknown if FoxO3a is involved in the development of neurons. Here, we report a role of FoxO3a during neuronal development in zebrafish. By using in situ hybridization, we revealed that FoxO3a transcripts in zebrafish were gradually confined to regions of the central nervous system during embryonic development, including the forebrain, midbrain, midbrain-hindbrain boundary and hindbrain. By using FoxO3a morpholino antisense oligonucleotides, we observed that FoxO3a loss-of-function led to neural developmental defects, including increased neural apoptosis as detected by acridine orange and terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling. These defects could be partially rescued by the injection of FoxO3a mRNA. In this study, we found that FoxO3a loss-of-function resulted in the decreased expression of neuronal markers as determined by in situ hybridization and relative quantitative real-time PCR. Furthermore, the activation of FoxO3a was required for the maintenance of neuron survival but not necessary for the induction of neurogenesis. Our results indicated that FoxO3a might be essential for the maintenance of neural development in zebrafish. Therefore, this work provides novel evidence of FoxO3a in the embryonic neurodevelopment from zebrafish to other mammals.
authors.affiliation: Laboratory of Integrated Bioscience, School of Life Science, Sun Yat-sen University, No. 135 West XinGang Road, Guangzhou 510275, China.
authors.forename: Kou
authors.initials: K
authors.lastname: Peng
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
authors.forename: Ling
authors.initials: L
authors.lastname: Long
authors.forename: Dong
authors.initials: D
authors.lastname: Li
authors.forename: Qiuli
authors.initials: Q
authors.lastname: Jia
authors.forename: Yidong
authors.initials: Y
authors.lastname: Wang
authors.forename: Qingyu
authors.initials: Q
authors.lastname: Shen
authors.forename: Yamei
authors.initials: Y
authors.lastname: Tang
authors.forename: Lu
authors.initials: L
authors.lastname: Wen
authors.forename: Hsiang-Fu
authors.initials: HF
authors.lastname: Kung
authors.forename: Ying
authors.initials: Y
authors.lastname: Peng
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics*; D001921:Brain / Q000166:cytology* / Q000196:embryology; D004625:Embryo, Nonmammalian; D047108:Embryonic Development / Q000187:drug effects / Q000502:physiology*; D051858:Forkhead Transcription Factors / Q000737:chemistry / Q000172:deficiency* / Q000235:genetics; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D055785:Gene Knockdown Techniques; D049452:Green Fluorescent Proteins / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D019006:Neural Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000737:chemistry / Q000172:deficiency* / Q000235:genetics
chemical_list: D051858:Forkhead Transcription Factors; D009419:Nerve Tissue Proteins; D019006:Neural Cell Adhesion Molecules; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D029961:Zebrafish Proteins; D049452:Green Fluorescent Proteins; D013482:Superoxide Dismutase