Revealing the biological features of the axolotl pancreas as a new research model
IntroductionThe pancreas plays a crucial role in digestion and blood glucose regulation. Current animal models, primarily mice and zebrafish, have limited the exploration of pancreatic biology from an evolutionary-developmental perspective. Tetrapod vertebrate axolotl (Ambystoma mexicanum) serves as...
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Frontiers Media S.A.
2025-01-01
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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.2025.1531903/full |
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| author | Hui Ma Hui Ma Hui Ma Guangcong Peng Yan Hu Binbin Lu Binbin Lu Yiying Zheng Yingxian Wu Weimin Feng Yu Shi Xiangyu Pan Li Song Ina Stützer Yanmei Liu Jifeng Fei Jifeng Fei Jifeng Fei |
| author_facet | Hui Ma Hui Ma Hui Ma Guangcong Peng Yan Hu Binbin Lu Binbin Lu Yiying Zheng Yingxian Wu Weimin Feng Yu Shi Xiangyu Pan Li Song Ina Stützer Yanmei Liu Jifeng Fei Jifeng Fei Jifeng Fei |
| author_sort | Hui Ma |
| collection | DOAJ |
| description | IntroductionThe pancreas plays a crucial role in digestion and blood glucose regulation. Current animal models, primarily mice and zebrafish, have limited the exploration of pancreatic biology from an evolutionary-developmental perspective. Tetrapod vertebrate axolotl (Ambystoma mexicanum) serves as a valuable model in developmental, regenerative, and evolutionary biology. However, the fundamental biology of the axolotl pancreas remains underexplored. This study aims to characterize the unique developmental, functional, and evolutionary features of the axolotl pancreas to expand the understanding of pancreatic biology.MethodsWe conducted morphological, histological, and transcriptomic analyses to investigate the axolotl pancreas. Pancreatic development was observed using in situ hybridization and immunostaining for key pancreatic markers. RNA sequencing was performed to profile global gene expression during larva and adult stages. And differential gene expression analysis was used to characterize the conserved and unique gene patterns in the axolotl pancreas. Functional assays, including glucose tolerance tests and insulin tolerance tests, were optimized for individual axolotls. To assess pancreatic gene function, Pdx1 mutants were generated using CRISPR/Cas9-mediated gene editing, and their effects on pancreatic morphology, endocrine cell populations, and glucose homeostasis were analyzed.ResultsThe axolotl pancreas contains all known pancreatic cell types and develops from dorsal and ventral buds. Both of buds contribute to exocrine and endocrine glands. The dorsal bud produces the major endocrine cell types, while the ventral bud generates α and δ cells, but not β cells. Differential gene expression analysis indicated a transition in global gene expression from pancreatic cell fate commitment and the cell cycle to glucose response, hormone synthesis, and secretion, following the development progression. Notably, the adult axolotl pancreas exhibits slower metabolic activity compared to mammals, as evidenced by the results of GTT and ITT. The mutation of Pdx1 resulted in hyperglycemia and a significant reduction in pancreatic cell mass, including a complete loss of endocrine cells, although it did not lead to a lethal phenotype.DiscussionThis study examines the axolotl pancreas, highlighting the conservation of pancreatic development. Our study highlights the unique features of the axolotl pancreas and broadens the scope of animal models available for pancreatic evolution and disease research. |
| format | Article |
| id | doaj-art-4495f855c7d446ceb46edf6329f27b8e |
| institution | Kabale University |
| issn | 2296-634X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj-art-4495f855c7d446ceb46edf6329f27b8e2025-01-31T06:40:25ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2025-01-011310.3389/fcell.2025.15319031531903Revealing the biological features of the axolotl pancreas as a new research modelHui Ma0Hui Ma1Hui Ma2Guangcong Peng3Yan Hu4Binbin Lu5Binbin Lu6Yiying Zheng7Yingxian Wu8Weimin Feng9Yu Shi10Xiangyu Pan11Li Song12Ina Stützer13Yanmei Liu14Jifeng Fei15Jifeng Fei16Jifeng Fei17Department of Pathology, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, ChinaBGI Research, Qingdao, ChinaSchool of Basic Medical Sciences, Southern Medical University, Guangzhou, ChinaKey Laboratory of Brain, Cognition and Education Sciences, Guangdong Key Laboratory of Mental Health and Cognitive Science, Ministry of Education, Institute for Brain Research and Rehabilitation, South China Normal University, Guangzhou, ChinaDepartment of Pathology, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, ChinaDepartment of Pathology, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, ChinaThe Innovation Centre of Ministry of Education for Development and Diseases, School of Medicine, South China University of Technology, Guangzhou, ChinaKey Laboratory of Brain, Cognition and Education Sciences, Guangdong Key Laboratory of Mental Health and Cognitive Science, Ministry of Education, Institute for Brain Research and Rehabilitation, South China Normal University, Guangzhou, ChinaKey Laboratory of Brain, Cognition and Education Sciences, Guangdong Key Laboratory of Mental Health and Cognitive Science, Ministry of Education, Institute for Brain Research and Rehabilitation, South China Normal University, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Medical Immunology and Molecular Diagnostics, Guangdong Medical University, Dongguan, ChinaKey Laboratory of Brain, Cognition and Education Sciences, Guangdong Key Laboratory of Mental Health and Cognitive Science, Ministry of Education, Institute for Brain Research and Rehabilitation, South China Normal University, Guangzhou, ChinaDepartment of Pathology, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, ChinaDepartment of Pathology, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, ChinaDeutsche Forschungsgemeinschaft (DFG)-Center for Regenerative Therapies Dresden, Technische Universität Dresden, Dresden, GermanyKey Laboratory of Brain, Cognition and Education Sciences, Guangdong Key Laboratory of Mental Health and Cognitive Science, Ministry of Education, Institute for Brain Research and Rehabilitation, South China Normal University, Guangzhou, ChinaDepartment of Pathology, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, ChinaSchool of Basic Medical Sciences, Southern Medical University, Guangzhou, ChinaThe Innovation Centre of Ministry of Education for Development and Diseases, School of Medicine, South China University of Technology, Guangzhou, ChinaIntroductionThe pancreas plays a crucial role in digestion and blood glucose regulation. Current animal models, primarily mice and zebrafish, have limited the exploration of pancreatic biology from an evolutionary-developmental perspective. Tetrapod vertebrate axolotl (Ambystoma mexicanum) serves as a valuable model in developmental, regenerative, and evolutionary biology. However, the fundamental biology of the axolotl pancreas remains underexplored. This study aims to characterize the unique developmental, functional, and evolutionary features of the axolotl pancreas to expand the understanding of pancreatic biology.MethodsWe conducted morphological, histological, and transcriptomic analyses to investigate the axolotl pancreas. Pancreatic development was observed using in situ hybridization and immunostaining for key pancreatic markers. RNA sequencing was performed to profile global gene expression during larva and adult stages. And differential gene expression analysis was used to characterize the conserved and unique gene patterns in the axolotl pancreas. Functional assays, including glucose tolerance tests and insulin tolerance tests, were optimized for individual axolotls. To assess pancreatic gene function, Pdx1 mutants were generated using CRISPR/Cas9-mediated gene editing, and their effects on pancreatic morphology, endocrine cell populations, and glucose homeostasis were analyzed.ResultsThe axolotl pancreas contains all known pancreatic cell types and develops from dorsal and ventral buds. Both of buds contribute to exocrine and endocrine glands. The dorsal bud produces the major endocrine cell types, while the ventral bud generates α and δ cells, but not β cells. Differential gene expression analysis indicated a transition in global gene expression from pancreatic cell fate commitment and the cell cycle to glucose response, hormone synthesis, and secretion, following the development progression. Notably, the adult axolotl pancreas exhibits slower metabolic activity compared to mammals, as evidenced by the results of GTT and ITT. The mutation of Pdx1 resulted in hyperglycemia and a significant reduction in pancreatic cell mass, including a complete loss of endocrine cells, although it did not lead to a lethal phenotype.DiscussionThis study examines the axolotl pancreas, highlighting the conservation of pancreatic development. Our study highlights the unique features of the axolotl pancreas and broadens the scope of animal models available for pancreatic evolution and disease research.https://www.frontiersin.org/articles/10.3389/fcell.2025.1531903/fullaxolotldiabetesglucose metabolismpancreas developmentPdx1 mutation |
| spellingShingle | Hui Ma Hui Ma Hui Ma Guangcong Peng Yan Hu Binbin Lu Binbin Lu Yiying Zheng Yingxian Wu Weimin Feng Yu Shi Xiangyu Pan Li Song Ina Stützer Yanmei Liu Jifeng Fei Jifeng Fei Jifeng Fei Revealing the biological features of the axolotl pancreas as a new research model Frontiers in Cell and Developmental Biology axolotl diabetes glucose metabolism pancreas development Pdx1 mutation |
| title | Revealing the biological features of the axolotl pancreas as a new research model |
| title_full | Revealing the biological features of the axolotl pancreas as a new research model |
| title_fullStr | Revealing the biological features of the axolotl pancreas as a new research model |
| title_full_unstemmed | Revealing the biological features of the axolotl pancreas as a new research model |
| title_short | Revealing the biological features of the axolotl pancreas as a new research model |
| title_sort | revealing the biological features of the axolotl pancreas as a new research model |
| topic | axolotl diabetes glucose metabolism pancreas development Pdx1 mutation |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2025.1531903/full |
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