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Essential function of Nr4a2 in subicular development and social novelty
Xi-Yue Liu1, Yun-Chao Tao1, Qiong Zhang2
1State Key Laboratory of Brain Function and Disorders, MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University, Shanghai 200032, China.
Journal of Advanced Research
|December 13, 2025
Summary
The orphan nuclear receptor Nr4a2 is crucial for subiculum proper (Sub) neuron development and function. Loss of Nr4a2 impairs social novelty behavior and disrupts Sub neuron identity and connectivity.
Area of Science:
- Neuroscience
- Molecular Biology
- Developmental Biology
Background:
- The subicular region is a key hippocampal output area with diverse neuronal subtypes.
- The developmental transcriptional programs governing subicular neuron specification are not well understood.
Purpose of the Study:
- To investigate the role of the orphan nuclear receptor Nr4a2 in subicular neuron development and function.
- To uncover the molecular mechanisms by which Nr4a2 regulates subicular neuron identity and connectivity.
Main Methods:
- Utilized Nr4a2 conditional knockout (CKO) mouse models.
- Employed RNA-sequencing, CUT&Tag, immunohistochemistry, slice electrophysiology, and behavioral assays.
- Investigated both embryonic development and adult function following Nr4a2 ablation.
Main Results:
- Nr4a2 is essential for establishing and maintaining the molecular identity of subiculum proper (Sub) neurons.
- Nr4a2 regulates the connectivity between subicular neurons and the retrosplenial cortex (Rsp).
- Loss of Nr4a2 leads to deficits in social novelty behavior and direct regulation of Sub-enriched genes.
Conclusions:
- Nr4a2 plays a critical role in the genetic specification and connectivity of Sub neurons.
- Dysfunction of Nr4a2 may be implicated in hippocampus-related neurodevelopmental disorders.
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