MAP7-driven cytoskeletal remodeling establishes epithelial polarity for male germ cell progression

Sertoli cells establish a specialized apical domain essential for organizing the seminiferous epithelium and supporting germ cell development, yet the underlying mechanisms remain poorly understood. We identify MAP7 as a key regulator of cytoskeletal integration required for apical domain formation. MAP7 localizes to apical microtubules without overlapping stable, acetylated tubulin. MAP7 loss disrupts apical architecture, causes ectopic tight junction expansion, and prevents lumen formation during the first wave of spermatogenesis. Although microtubule stability is largely preserved in Map7 -deficient Sertoli cells, their orientation is severely disrupted, indicating that MAP7 directs dynamic remodeling for proper apical organization. Proteomics shows that MAP7 associates with MYH9 and MYH10, and MYH9, normally enriched at luminal regions where microtubules and F-actin converge, becomes diffuse by Map7 knockout, suggesting that MAP7 mediates spatial coupling of microtubules and actomyosin. Single-cell RNA sequencing shows that Sertoli cell differentiation largely persists without MAP7, whereas germ cells exhibit delayed meiotic progression with expanded pachytene subtypes. These findings position MAP7 as a cytoskeletal integrator linking epithelial polarity to germ cell progression, highlighting how tissue organization underlies fertility.