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Peng, K, Li, Y, Long, L, Li, D, Jia, Q, Wang, Y, Shen, Q, Tang, Y, Wen, L, Kung, HF and Peng, Y (2010) Knockdown of FoxO3a induces increased neuronal apoptosis during embryonic development in zebrafish. Neurosci. Lett. 484:98-103
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.
Amino Acid Sequence; Animals; Animals, Genetically Modified; Apoptosis/drug effects; Apoptosis/genetics; Brain/cytology; Brain/embryology; Embryo, Nonmammalian; Embryonic Development/drug effects; Embryonic Development/physiology; Forkhead Transcription Factors/chemistry; Forkhead Transcription Factors/deficiency; Forkhead Transcription Factors/genetics; Gene Expression Regulation, Developmental/drug effects; Gene Knockdown Techniques; Green Fluorescent Proteins/genetics; Nerve Tissue Proteins/genetics; Nerve Tissue Proteins/metabolism; Neural Cell Adhesion Molecules/genetics; Neural Cell Adhesion Molecules/metabolism; Neurons/drug effects; Neurons/physiology; Oligonucleotides, Antisense/pharmacology; RNA, Messenger/metabolism; Superoxide Dismutase/genetics; Superoxide Dismutase/metabolism; Zebrafish; Zebrafish Proteins/chemistry; Zebrafish Proteins/deficiency; Zebrafish Proteins/genetics