engleski

The role of Npas4 in brain development

Purpose: To elucidate the developmental role a NPAS4 which is a member of the neural transcription factor bHLH / PAS family. These factors have key roles during development and in the mature organism. NPAS4 expression is restricted to brain, with minor levels detected in testes. NPAS4 expression is specifically expressed in the neurogenic regions of the brain. In adults NPAS4 expression is induced in response to environmental stresses such as ischaemia and seizure. The interest of this study is the role of NPAS4 in the developing embryo. Methods: Zebrafish embryos (n=100s) were injected with three different NPAS4 antisense morpholino oligonucleotides at the single cell stage to reduce expression. Markers of brain development were analysed by whole-mount in-situ hybridisation. Results: Firstly, NPAS4 expression was detected in the developing brain of Danio rerio. Zebrafish embryos at 24hpf displayed reduced brain size and organisation. Morphogens responsible for patterning and neural cell fates had altered expression levels as a result of NPAS4 knock-down. The change in expression patterns of shh and dlx molecules supported the observed morphant phenotype of a reduction in development of the diencephalon. Conclusion: NPAS4 does have a developmental role in forebrain.

Zebrafish, npas4a, neurodevelopment

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