ArticleJournal of cell communication and signaling2022
Dysregulation of Notch-FGF signaling axis in germ cells results in cystic dilation of the rete testis in mice.
Article in Journal of cell communication and signaling, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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5 citing papers in PubMed.
- Single-nucleus RNA sequencing reveals the underlying roadmap of early gonadal differentiation in teleost.Science China. Life sciences · 2026Article
- A comparative analysis of genes differentially expressed between rete testis cells and Sertoli cells of the mouse testis.Scientific reports · 2023Article
- Rhox8 homeobox gene ablation leads to rete testis abnormality and male subfertility in mice†.Biology of reproduction · 2023Article
- Comparative anatomy on the development of sperm transporting pathway between the testis and mesonephros.Histochemistry and cell biology · 2022Article
- Aberrant activation of KRAS in mouse theca-interstitial cells results in female infertility.Frontiers in physiology · 2022Article
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10 authors.
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Abstract
Numb (Nb) and Numb-like (Nbl) are functionally redundant adaptor proteins that critically regulate cell fate and morphogenesis in a variety of organs. We selectively deleted Nb and Nbl in testicular germ cells by breeding Nb/Nbl floxed mice with a transgenic mouse line Tex101-Cre. The mutant mice developed unilateral or bilateral cystic dilation in the rete testis (RT). Dye trace indicated partial blockages in the testicular hilum. Morphological and immunohistochemical evaluations revealed that the lining epithelium of the cysts possessed similar characteristics of RT epithelium, suggesting that the cyst originated from dilation of the RT lumen. Spermatogenesis and the efferent ducts were unaffected. In comparisons of isolated germ cells from mutants to control mice, the Notch activity considerably increased and the expression of Notch target gene Hey1 significantly elevated. Further studies identified that germ cell Fgf4 expression negatively correlated the Notch activity and demonstrated that blockade of FGF receptors mediated FGF4 signaling induced enlargement of the RT lumen in vitro. The crucial role of the FGF4 signaling in modulation of RT development was verified by the selective germ cell Fgf4 ablation, which displayed a phenotype similar to that of germ cell Nb/Nbl null mutant males. These findings indicate that aberrant over-activation of the Notch signaling in germ cells due to Nb/Nbl abrogation impairs the RT development, which is through the suppressing germ cell Fgf4 expression. The present study uncovers the presence of a lumicrine signal pathway in which secreted/diffusible protein FGF4 produced by germ cells is essential for normal RT development.
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