engleski

Npas4 regulates the expression of Sox1 in an early neural progenitor cell population during neural differentiation of mouse embryonic stem cells

Purpose: In the adult organism, the activity- dependent transcription factor Npas4 plays an important role in several key aspects of neurobiology including inhibitory synapse formation, neuroprotection and memory. However, little is known regarding the role of Npas4 during neurodevelopment. In this study, we used neural differentiation of embryonic stem cells (ESCs) as a model to investigate the expression and function of Npas4 during early development. Methods: Noggininduced differentiation of human ESCs and differentiation of mouse ESCs as an adherent monolayer were used as in vitro models of early embryonic development. Results: We found that while Npas4 is not expressed by undifferentiated ESCs, it becomes transiently up regulated during neural differentiation of both mouse and human ESCs (n=3) at a stage of differentiation that is characterised by proliferation of neural progenitor cells (NPCs). Knock down of Npas4 expression in mouse ESCs undergoing neural differentiation (n>3) resulted in a decrease in the percentage of cells expressing the neuroectoderm marker Sox1, though expression of Nestin, a marker of more mature NPCs, was not affected. Conclusion: Our findings suggest that Npas4 acts upstream of Sox1 during neural differentiation and further suggest a potential role for Npas4 in aspects of NPC maintenance and/or differentiation. Here we provide the first evidence that Npas4 is expressed during development by a population of early NPCs and that it may have a developmental role that is unrelated to its function in the adult brain

Npas4 ; mouse embryonic stem cells ; neural differentiation

nije evidentirano