非表示:
キーワード:
Actomyosin/*metabolism
Animals
*Cell Movement
Cell Proliferation
Epithelial Cells/*metabolism/ultrastructure
Female
Gene Expression Regulation, Developmental
Gestational Age
Hypertrophy
Keratinocytes/metabolism/ultrastructure
Mammary Glands, Animal/embryology/*metabolism/ultrastructure
*Mechanotransduction, Cellular
Mice, Inbred C57BL
Mice, Transgenic
Microscopy, Confocal
Microscopy, Electron, Scanning
Microscopy, Fluorescence
Morphogenesis
要旨:
The mammary gland develops from the surface ectoderm during embryogenesis and proceeds through morphological phases defined as placode, hillock, bud, and bulb stages followed by branching morphogenesis. During this early morphogenesis, the mammary bud undergoes an invagination process where the thickened bud initially protrudes above the surface epithelium and then transforms to a bulb and sinks into the underlying mesenchyme. The signaling pathways regulating the early morphogenetic steps have been identified to some extent, but the underlying cellular mechanisms remain ill defined. Here, we use 3D and 4D confocal microscopy to show that the early growth of the mammary rudiment is accomplished by migration-driven cell influx, with minor contributions of cell hypertrophy and proliferation. We delineate a hitherto undescribed invagination mechanism driven by thin, elongated keratinocytes-ring cells-that form a contractile rim around the mammary bud and likely exert force via the actomyosin network. Furthermore, we show that conditional deletion of nonmuscle myosin IIA (NMIIA) impairs invagination, resulting in abnormal mammary bud shape.
