2. Academic Validation
  3. HIF signaling overactivation inhibits lateral line neuromast development through Wnt in zebrafish

HIF signaling overactivation inhibits lateral line neuromast development through Wnt in zebrafish

  • Gene. 2023 Dec 12:898:148077. doi: 10.1016/j.gene.2023.148077.
Ran Zhang 1,  Ziyue Ma 1,  Jian Wang 2,  Chunxin Fan 3
Affiliations

Affiliations

  • 1 Key Laboratory of Exploration and Utilization of Aquatic Genetic Resources, Ministry of Education, Shanghai Ocean University, Shanghai, China; International Research Center for Marine Biosciences, Ministry of Science and Technology, Shanghai Ocean University, Shanghai, China.
  • 2 Key Laboratory of Exploration and Utilization of Aquatic Genetic Resources, Ministry of Education, Shanghai Ocean University, Shanghai, China; International Research Center for Marine Biosciences, Ministry of Science and Technology, Shanghai Ocean University, Shanghai, China. Electronic address: J_wang@shou.edu.cn.
  • 3 Key Laboratory of Exploration and Utilization of Aquatic Genetic Resources, Ministry of Education, Shanghai Ocean University, Shanghai, China; International Research Center for Marine Biosciences, Ministry of Science and Technology, Shanghai Ocean University, Shanghai, China; Marine Biomedical Science and Technology Innovation Platform of Lingang New Area, Shanghai, China. Electronic address: cxfan@shou.edu.cn.
PMID: 38097093 DOI: 10.1016/j.gene.2023.148077
Abstract

The lateral line is critical for prey detection, predator avoidance, schooling, and rheotaxis behavior in fish. As similar to hair cells in the mammalian inner ear, the lateral line sensory organ called neuromasts is a popular model for hair cell regeneration. However, the mechanism of lateral line development has not been fully understood. In this study, we showed for the first time that hypoxia-inducible factor (HIF) signaling is involved in lateral line development in zebrafish. hif1ab and epas1b were highly expressed in neuromasts during lateral line development. Hypoxia response induced by a prolyl hydroxylase domain-containing proteins (PHD) inhibitor treatment or vhl gene knockout significantly reduced hair cells and support cells in neuromast during lateral line development. In addition, inhibition of Hif-1α or Epas1 could partially rescue hair cells in the larvae with increased HIF activity, respectively. Moreover, the support cell proliferation and the expression of Wnt target genes decreased in vhl mutants which suggests that Wnt signaling mediated the role of HIF signaling in lateral line development. Collectively, our results demonstrate that HIF signaling overactivation inhibits lateral line development in zebrafish and suggest that inhibition of HIF signaling might be a potential therapeutic method for hair cell death.

Keywords

HIF signaling; Hair cells; Lateral line; Support cells; Vhl.

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