The ultra-conserved lncRNA <i>Crnde</i> regulates neural differentiation by targeting <i>Gbx2</i> during embryonic development of the thalamus

Wen-Zhu Hu; Ya-Yun Gu; Yuan-Lin He; Yuan Hong; Yue-Wen He; Zi-Cheng Zhang; Yuan-Hao Wang; Jia-Ning Sun; Xiao Han; Yan Liu; Zhi-Bin Hu

doi:10.1016/j.jgg.2026.02.002

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The ultra-conserved lncRNA Crnde regulates neural differentiation by targeting Gbx2 during embryonic development of the thalamus

doi: 10.1016/j.jgg.2026.02.002

Wen-Zhu Hu^a,b,c,
Ya-Yun Gu^b,c,d,
Yuan-Lin He^b,c,
Yuan Hong^e,f,
Yue-Wen He^b,
Zi-Cheng Zhang^b,
Yuan-Hao Wang^e,
Jia-Ning Sun^b,
Xiao Han^d,e,
Yan Liu^b,d,e,
Zhi-Bin Hu^a,b,c,d

a. Department of Epidemiology, School of Public Health, Southeast University, Nanjing, Jiangsu 211189, China;
b. State Key Laboratory of Reproductive Medicine and Offspring Health, Nanjing Medical University, Nanjing, Jiangsu 211166, China;
c. Department of Epidemiology and Biostatistics, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu 211166, China;
d. State Key Laboratory of Reproductive Medicine and Offspring Health (Suzhou Centre), The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, Jiangsu 215002, China;
e. Institute of Stem Cell and Neural Regeneration, School of Pharmacy, Nanjing Medical University, Nanjing, Jiangsu 211166, China;
f. Department of Pharmacy, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, Jiangsu 215002, China

Funds:

This work was funded by the National Key Project of Research and Development Program of China (2024YFC2706800), the Program of the National Natural Science Foundation of China Grants (82221005), the National Key Project of Research and Development Program of China (2021YFC2700600, 2021YFA1101800, 2021YFA1101801), and the National Natural Science Foundation of China Grants (82325015, 82401794). This study used data generated by the DECIPHER community. A list of participants who contributed to the generation of the data can be obtained from http://decipher.sanger.ac.uk. The project was funded by the Wellcome Trust. We thank Yiqiang Cui, State Key Laboratory of Reproductive Medicine, Nanjing Medical University, for technical support in constructing Crnde knockout mice. We thank Junhai Han and Wenhua Liu, School of Life Science and Technology, Southeast University, for their support of embryo electrotransfer technology.

Received Date: 2025-07-09
Accepted Date: 2026-02-01
Rev Recd Date: 2026-02-01

Available Online: 2026-02-09

Abstract

Abstract

The thalamus regulates sensory processing, cognition, and sleep, yet the molecular mechanisms underlying its development remain incompletely understood. Long noncoding RNAs (lncRNAs), particularly evolutionarily conserved ones, are highly enriched in the brain. Using public mRNA databases, we screen for lncRNAs with embryonic brain expression and harboring ultraconserved non-coding elements (UCNEs) in humans and mice, identifying colorectal neoplasia differentially expressed (Crnde). It exhibits stage-specific upregulation in the embryonic thalamus. The Database of Genomic Variation and Phenotype in Humans using Ensembl Resources (DECIPHER) database suggests a potential association between Crnde and intellectual disability. Crnde-deficient mice display anxiety-like behaviors and spatial memory deficits. Furthermore, Crnde ablation increases progenitor cell numbers and impairs neuronal differentiation during embryonic thalamic development. Mechanistically, Crnde modulates the mRNA expression of gastrulation brain homeobox 2 (Gbx2), a gene critical for thalamic development. Collectively, our results implicate lncRNA Crnde in the proper progression of embryonic thalamic development in mice.
- Neurodevelopmental disorders,
- Intellectual disability,
- Long noncoding RNA,
- Crnde,
- Thalamus development,
- Neuronal differentiation

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