2. Academic Validation
  3. Irg1l regulates neuromast size via metabolic reprogramming to promote supporting cell proliferation

Irg1l regulates neuromast size via metabolic reprogramming to promote supporting cell proliferation

  • J Cell Biol. 2025 Dec 1;224(12):e202501122. doi: 10.1083/jcb.202501122.
Xin Wang # 1,  Ruijun Shi # 1,  Yuqing Xiang # 2,  Yajing Gao # 2,  Guoqiang Wan 3,  Shan Sun 4,  Dong Liu 1 2
Affiliations

Affiliations

  • 1 Institute of Special Environmental Medicine, Affiliated Hospital 2, Nantong University , Nantong, China.
  • 2 Nantong Laboratory of Development and Diseases, School of Life Sciences, Co-innovation Center of Neuroregeneration, Nantong University, Nantong, China.
  • 3 State Key Laboratory of Pharmaceutical Biotechnology, Department of Otolaryngology-Head and Neck Surgery, Jiangsu Provincial Key Medical Discipline (Laboratory), The Affiliated Drum Tower Hospital of Medical School, Model Animal Research Center of Medical School, Nanjing University, Nanjing, China.
  • 4 ENT institute and Otorhinolaryngology Department of Eye and ENT Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan University, Shanghai, China.
  • # Contributed equally.
PMID: 41147954 DOI: 10.1083/jcb.202501122
Abstract

One of the most basic principles in embryonic development is ensuring the proper size of tissues and organs to meet functional needs. So far, an Endogenous Metabolite regulating organ size has not been described. The current study highlights itaconate, the product of Irg1, in regulating zebrafish neuromast size. Single-cell transcriptomic Sequencing analysis of Enzymes catalyzing metabolic processes revealed that irg1l, a homolog of Irg1, is highly expressed in supporting cells of developing neuromast in zebrafish. Deficiency of irg1l reduced the size of the neuromast and caused auditory dysfunction. Conversely, overexpression of irg1l resulted in increased size due to excessive proliferation of supporting cells. Notably, 4-octyl itaconate (4-OI), an itaconate derivative, treatment recapitulates the phenotype of irg1l overexpression and increases the neuromast size. Finally, we revealed that the Irg1l/itaconate axis induces metabolic reprogramming to promote activation of the YAP, drive supporting cell proliferation, and enlarge neuromast size. These findings provide a novel insight into the role of metabolites in organ development.

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