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SignificanceThe ability of cells to migrate collectively underlies many biological processes. The parapineal is a small group of cells that requires Fgf8 to migrate from the midline to the left side of the zebrafish forebrain. Studying the dynamics of FGF pathway activation reveals that FGF activity is restricted to a few left-sided parapineal cells. Global activation of the FGF pathway interferes with parapineal migration in wild-type embryos, while focal activation in few parapineal cells can restore migration in fgf8−/− mutants, indicating that FGF pathway activation in leading cells is required for collective migration. We show that focal FGF activity is influenced by left-sided Nodal signaling. Our findings may apply to other contexts of FGF-dependent cell migration during development or metastasis.

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Aim:To examine the therapeutic/preventive potential of liposome-encapsulated spironolactone (SP; Lipo-SP) for acute lung injury (ALI) and fibrosis. Materials & methods: Lipo-SP was prepared by the film-ultrasonic method, and physicochemical and pharmacokinetic characterized for oral administration (10 and 20 mg/kg for SPloaded liposome; 20 mg/kg for free SP) in a mouse model bleomycin-induced ALI. Results: Lipo-SP enhanced bioavailability of SP with significant amelioration in lung pathology. Mechanistically, SP-mediated mineralocorticoid receptor antagonism contributes to inflammatory monocyte/macrophage modulation via an inhibitory effect on Ly6C hi monocytosis-directed M2 polarization of alveolar macrophages. Moreover, Lipo-SP at lower dose (10 mg/kg) exhibited more improvement in body weight gain. Conclusion: Our data highlight Lipo-SP as a promising approach with therapeutic/preventive potential for ALI and fibrosis.