Spatiotemporal regulation by downstream genes of Prok2 in the olfactory system: from development to function
IntroductionOlfaction 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 uncle...
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Frontiers Media S.A.
2025-07-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2025.1550845/full |
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| author | Bo-Ra Kim Min-Seok Rha Min-Seok Rha Hyung-Ju Cho Hyung-Ju Cho Joo-Heon Yoon Joo-Heon Yoon Chang-Hoon Kim Chang-Hoon Kim Chang-Hoon Kim Chang-Hoon Kim |
| author_facet | Bo-Ra Kim Min-Seok Rha Min-Seok Rha Hyung-Ju Cho Hyung-Ju Cho Joo-Heon Yoon Joo-Heon Yoon Chang-Hoon Kim Chang-Hoon Kim Chang-Hoon Kim Chang-Hoon Kim |
| author_sort | Bo-Ra Kim |
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| description | IntroductionOlfaction 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.MethodsWe 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.ResultsThe 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.DiscussionOverall, these findings reveal the role of Prok2 in olfactory system organization and elucidate how olfactory development defects translate to olfactory function. |
| format | Article |
| id | doaj-art-5e3a8992b30e4381b096e186fe8b7d3c |
| institution | DOAJ |
| issn | 2296-634X |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj-art-5e3a8992b30e4381b096e186fe8b7d3c2025-08-20T03:13:35ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2025-07-011310.3389/fcell.2025.15508451550845Spatiotemporal regulation by downstream genes of Prok2 in the olfactory system: from development to functionBo-Ra Kim0Min-Seok Rha1Min-Seok Rha2Hyung-Ju Cho3Hyung-Ju Cho4Joo-Heon Yoon5Joo-Heon Yoon6Chang-Hoon Kim7Chang-Hoon Kim8Chang-Hoon Kim9Chang-Hoon Kim10The Airway Mucus Institute, Yonsei University College of Medicine Seoul, Seoul, Republic of KoreaThe Airway Mucus Institute, Yonsei University College of Medicine Seoul, Seoul, Republic of KoreaDepartment of Otorhinolaryngology, Yonsei University College of Medicine, Seoul, Republic of KoreaThe Airway Mucus Institute, Yonsei University College of Medicine Seoul, Seoul, Republic of KoreaDepartment of Otorhinolaryngology, Yonsei University College of Medicine, Seoul, Republic of KoreaThe Airway Mucus Institute, Yonsei University College of Medicine Seoul, Seoul, Republic of KoreaDepartment of Otorhinolaryngology, Yonsei University College of Medicine, Seoul, Republic of KoreaThe Airway Mucus Institute, Yonsei University College of Medicine Seoul, Seoul, Republic of KoreaDepartment of Otorhinolaryngology, Yonsei University College of Medicine, Seoul, Republic of KoreaKorea Mouse Sensory Phenotyping Center, Yonsei University College of Medicine, Seoul, Republic of KoreaHuman Microbiome Center, Yonsei University College of Medicine, Seoul, Republic of KoreaIntroductionOlfaction 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.MethodsWe 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.ResultsThe 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.DiscussionOverall, these findings reveal the role of Prok2 in olfactory system organization and elucidate how olfactory development defects translate to olfactory function.https://www.frontiersin.org/articles/10.3389/fcell.2025.1550845/fullprokineticin 2 genekallman syndromeolfactory dysfunctionolfactory sensory neuronembryonic developmentspatiotemporal regulation |
| spellingShingle | Bo-Ra Kim Min-Seok Rha Min-Seok Rha Hyung-Ju Cho Hyung-Ju Cho Joo-Heon Yoon Joo-Heon Yoon Chang-Hoon Kim Chang-Hoon Kim Chang-Hoon Kim Chang-Hoon Kim Spatiotemporal regulation by downstream genes of Prok2 in the olfactory system: from development to function Frontiers in Cell and Developmental Biology prokineticin 2 gene kallman syndrome olfactory dysfunction olfactory sensory neuron embryonic development spatiotemporal regulation |
| title | Spatiotemporal regulation by downstream genes of Prok2 in the olfactory system: from development to function |
| title_full | Spatiotemporal regulation by downstream genes of Prok2 in the olfactory system: from development to function |
| title_fullStr | Spatiotemporal regulation by downstream genes of Prok2 in the olfactory system: from development to function |
| title_full_unstemmed | Spatiotemporal regulation by downstream genes of Prok2 in the olfactory system: from development to function |
| title_short | Spatiotemporal regulation by downstream genes of Prok2 in the olfactory system: from development to function |
| title_sort | spatiotemporal regulation by downstream genes of prok2 in the olfactory system from development to function |
| topic | prokineticin 2 gene kallman syndrome olfactory dysfunction olfactory sensory neuron embryonic development spatiotemporal regulation |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2025.1550845/full |
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