The Role of ATF3 in Neuronal Differentiation and Development of Neuronal Networks in Opossum Postnatal Cortical Cultures

Int. J. Mol. Sci., 2022 · DOI: 10.3390/ijms23094964 · Published: April 29, 2022

Regenerative Medicine Neurology Genetics

Simple Explanation

This study investigates the role of Activating Transcription Factor 3 (ATF3) in the development and regeneration of neurons using cortical cultures from neonatal opossums. The researchers found that ATF3 is highly expressed in early differentiating neurons and plays a crucial role in neurite outgrowth, differentiation, and regeneration after injury. The study also revealed that the location of ATF3 within the cell changes as neurons mature, shifting from the nucleus in neuronal progenitors to the cytoplasm in mature neurons.

Study Duration

Up to 1 month in vitro

Participants

Neonatal opossums (Monodelphis domestica) P5-6 and P16-17

Evidence Level

In vitro study

Key Findings

1
RAG and ATF genes are differentially expressed in early differentiated neurons versus undifferentiated neurospheres, with ATF3 showing the highest difference in expression.
2
ATF3 intracellular localization shifts from nuclear in neuronal progenitors to cytoplasmic in more mature neurons during neuronal differentiation.
3
Inhibition of ATF3 reduces neurite outgrowth and differentiation, and increases cell death in early differentiating cortical neuronal cultures.

Research Summary

This study investigates the role of ATF3 in neuronal differentiation, network formation, and regeneration using postnatal opossum cortical cultures. The researchers found that ATF3 is differentially expressed and localized during neuronal differentiation and that it plays an important role in neurite outgrowth and regeneration after injury. The study also introduces a novel in vitro injury model with postnatal neurons that have an intrinsic ability to regenerate, providing a platform for studying CNS regeneration mechanisms.

Practical Implications

Understanding CNS Regeneration

The study provides insights into the molecular mechanisms underlying CNS regeneration, particularly the role of ATF3 and other RAG/ATF transcription factors.

Potential Therapeutic Targets

The findings suggest that ATF3 could be a potential therapeutic target for promoting neuronal regeneration and recovery after CNS injuries.

In Vitro Model for Drug Screening

The established opossum primary cortical cultures and neuroregeneration assay offer a valuable in vitro model for screening drugs and investigating molecular pathways involved in neuronal differentiation and regeneration.

Study Limitations

1
The study is limited to in vitro experiments, and further in vivo studies are needed to confirm the findings.
2
The study focuses on ATF3, and further research is needed to investigate the role of other RAG and ATF/CREB family members.
3
The study uses opossum cortical neurons, and the results may not be directly applicable to other species or brain regions.

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