Zhe Wang, Yue Zhang, Min Zhang, Yuhong Shi, Zhenyu Cai, Wenteng Xu, Xihong Li, Na Wang
Chinese tongue sole (Cynoglossus semilaevis) is a unique model for studying the mechanisms of sex determination and sexual size dimorphism (SSD). Preliminary transcriptome and Weighted Gene Co-expression Network Analysis (WGCNA) analyses have identified the neurotrophic tropomyosin receptor kinase 2 gene (ntrk2), whose mutation leads to disorders such as obesity and developmental delays. To better understand the role of neurotrophic tropomyosin receptor kinase (ntrk) family genes in C. semilaevis SSD, we identified and characterized the ntrk gene family and its brain-derived neurotrophic factor (bdnf) ligand. As a result, six ntrk homologous genes (ntrk1, ntrk2a-w, ntrk2a-z, ntrk2b, ntrk3a, ntrk3b) were identified in C. semilaevis at the genome-wide level. Expression profiling revealed predominant brain and pituitary expression of ntrk2 and ntrk3, with ntrk2a-w exhibiting female-specific patterns in the telencephalon and hypothalamus, and ntrk2a-z/ntrk2b widely expressed in all five brain regions. Six different transcripts for bdnf, the primary ligand for ntrk2, were also characterized. Quantitative RT-PCR further revealed sex-specific expression patterns of bdnf1-6 in the five brain regions. Interaction network prediction showed that ntrk could interact with key molecules related to growth and development including BDNF, NGFa, NGFb, and FGFR. Knockdown of ntrk2 and bdnf in C. semilaevis brain cells significantly reduced the expression of pro-opiomelanocortin (pomc), AMP-activated protein kinase α1 subunit (prkaa1), and leptin receptor (lepr)-genes encoding key components of the leptin-melanocortin energy homeostasis pathway. This suggests that the BDNF/NTRK2 signaling axis may centrally regulate feeding and metabolism in C. semilaevis. Our findings provide molecular and functional clues for exploring the neuroendocrine mechanisms underlying sexual size dimorphism in this flatfish.