ArticleStem cell research & therapy2014
A reduction in Npas4 expression results in delayed neural differentiation of mouse embryonic stem cells.
Article in Stem cell research & therapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 17 citations in OpenAlex.
- Light-activated tetanus neurotoxin for conditional proteolysis and inducible synaptic inhibition in vivo.Nature methods · 2026Article
- NPAS4 Depletion in POMC Neurons Protects From Obesity and Alters the Feeding-regulated Transcriptome in Male Mice.Endocrinology · 2025Article
- Profound downregulation of neural transcription factor Npas4 and Nr4a family in fetal mice neurons infected with Zika virus.PLoS neglected tropical diseases · 2021Article
- Prenatal one-carbon metabolism dysregulation programs schizophrenia-like deficits.Molecular psychiatry · 2018Article
- Propofol Alters Long Non-Coding RNA Profiles in the Neonatal Mouse Hippocampus: Implication of Novel Mechanisms in Anesthetic-Induced Developmental Neurotoxicity.Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology · 2018Article
- miR-744 and miR-224 Downregulate Npas4 and Affect Lineage Differentiation Potential and Neurite Development During Neural Differentiation of Mouse Embryonic Stem Cells.Molecular neurobiology · 2017Article
- Combination of RNA Interference and Stem Cells for Treatment of Central Nervous System Diseases.Genes · 2017Review
- The Role of the Neuroprotective Factor Npas4 in Cerebral Ischemia.International journal of molecular sciences · 2015Review
- Article
- Activity-dependent expression of neuronal PAS domain-containing protein 4 (npas4a) in the developing zebrafish brain.Frontiers in neuroanatomy · 2014Article
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Authors and funding
6 authors at 2 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
introductionNpas4 is a calcium-dependent transcription factor expressed within neurons of the brain where it regulates the expression of several genes that are important for neuronal survival and synaptic plasticity. It is known that in the adult brain Npas4 plays an important role in several key aspects of neurobiology including inhibitory synapse formation, neuroprotection and memory, yet very little is known about the role of Npas4 during neurodevelopment. The aim of this study was to examine the expression and function of Npas4 during nervous system development by using a combination of in vivo experiments in the developing mouse embryo and neural differentiation of embryonic stem cells (ESCs) as an in vitro model of the early stages of embryogenesis.
methodsTwo different neural differentiation paradigms were used to investigate Npas4 expression during neurodevelopment in vitro; adherent monolayer differentiation of mouse ESCs in N2B27 medium and Noggin-induced differentiation of human ESCs. This work was complemented by direct analysis of Npas4 expression in the mouse embryo. The function of Npas4 in the context of neurodevelopment was investigated using loss-of-function experiments in vitro. We created several mouse ESC lines in which Npas4 expression was reduced during neural differentiation through RNA interference and we then analyzed the ability of these Npas4 knockdown mouse ESCs lines to undergo neural differentiation.
resultsWe found that while Npas4 is not expressed in undifferentiated ESCs, it becomes transiently up-regulated during neural differentiation of both mouse and human ESCs at a stage of differentiation that is characterized by proliferation of neural progenitor cells. This was corroborated by analysis of Npas4 expression in the mouse embryo where the Npas4 transcript was detected specifically in the developing forebrain beginning at embryonic day 9.5. Finally, knockdown of Npas4 expression in mouse ESCs undergoing neural differentiation affected their ability to differentiate appropriately, resulting in delayed neural differentiation.
conclusionsHere we provide the first evidence that Npas4 is expressed during embryonic development and that it may have a developmental role that is unrelated to its function in the adult brain.
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