ORIGINAL RESEARCH article
Front. Cell Dev. Biol.
Sec. Embryonic Development
Volume 13 - 2025 | doi: 10.3389/fcell.2025.1550845
This article is part of the Research TopicNeurodevelopment: From Stem Cells to Signaling and BeyondView all 6 articles
Spatiotemporal Regulation by Downstream Genes of Prok2 in the Olfactory System: From Development to Function
Provisionally accepted
- 1The Airway Mucus Institute, Yonsei University College of Medicine, Seoul, Republic of Korea
- 2Department of Otorhinolaryngology, Yonsei University College of Medicine, Seoul, Republic of Korea
- 3Korea Mouse Sensory Phenotyping Center, Yonsei University College of Medicine, Seoul, Republic of Korea
- 4Human Microbiome Center, Yonsei University College of Medicine, Seoul, Republic of Korea
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Olfaction is important for the quality of life; however, in Kallmann syndrome (KS), defective development results in olfactory dysfunction. Notably, the mechanism underlying olfactory development, especially in the olfactory epithelium (OE), which detects olfactory signals, remains unclear. Mutations in PROK2, which encodes prokineticin-2, have been identified in approximately 9% of the KS patients with olfactory defects. Methods: We examined olfactory function and analyzed the causes of olfactory dysfunction based on spatiotemporal development and gene expression changes in Prok2 knockout (KO) model mice with KS. Results: The ability of the OE to detect olfactory signals was diminished in adult Prok2 KO mice. Maturation of olfactory sensory neurons (OSNs) in the OE and formation of glomeruli in the olfactory bulb (OB) in adult Prok2 KO mice were disrupted, thus causing olfactory dysfunction. Furthermore, molecular analysis of Prok2 KO mice during embryonic development revealed abnormal development of OB layers and diminished differentiation to mature OSNs in the OE at the later stage, which caused defects in the entire olfactory system. Remarkably, downstream signaling genes of Prok2, including intermediate filament genes and genes expressed in the putative OB, were found to mediate olfactory system organization. Discussion: Overall, these findings reveal the role of Prok2 in olfactory system organization and elucidate how olfactory development defects translate to olfactory function.
Keywords: prokineticin 2 gene, Kallman syndrome, olfactory dysfunction, olfactory sensory neuron, Embryonic Development, Spatiotemporal regulation, Transcriptomic (RNA-Seq), intermediate filament (IF)
Received: 24 Dec 2024; Accepted: 07 Jul 2025.
Copyright: © 2025 Kim, Rha, Cho, YOON and Kim. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Chang-Hoon Kim, The Airway Mucus Institute, Yonsei University College of Medicine, Seoul, Republic of Korea
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