Institute of Biotechnology, Helsinki Institute of Life Sciences (HiLIFE), 00014 University of Helsinki, Helsinki, Finland.
Department of Biosciences and Nutrition, Karolinska Institutet, 141 83 Huddinge, Sweden.
Development. 2021 Jun 15;148(12). doi: 10.1242/dev.199281.
Epithelial attachment to the basement membrane (BM) is essential for mammary gland development, yet the exact roles of specific BM components remain unclear. Here, we show that Laminin α5 (Lama5) expression specifically in the luminal epithelial cells is necessary for normal mammary gland growth during puberty, and for alveologenesis during pregnancy. Lama5 loss in the keratin 8-expressing cells results in reduced frequency and differentiation of hormone receptor expressing (HR+) luminal cells. Consequently, Wnt4-mediated crosstalk between HR+ luminal cells and basal epithelial cells is compromised during gland remodeling, and results in defective epithelial growth. The effects of Lama5 deletion on gland growth and branching can be rescued by Wnt4 supplementation in the in vitro model of branching morphogenesis. Our results reveal a surprising role for BM-protein expression in the luminal mammary epithelial cells, and highlight the function of Lama5 in mammary gland remodeling and luminal differentiation.
上皮细胞与基底膜（BM）的附着对于乳腺发育至关重要，但特定 BM 成分的确切作用仍不清楚。在这里，我们表明层粘连蛋白 α5（Lama5）在腔上皮细胞中的特异性表达对于青春期正常乳腺生长和妊娠期间的肺泡发生是必需的。角蛋白 8 表达细胞中 Lama5 的缺失导致激素受体表达（HR+）腔上皮细胞的频率和分化减少。因此，Wnt4 介导的 HR+腔上皮细胞和基底上皮细胞之间的串扰在乳腺重塑过程中受到损害，导致上皮细胞生长缺陷。在分支形态发生的体外模型中，Wnt4 的补充可以挽救 Lama5 缺失对腺体生长和分支的影响。我们的研究结果揭示了 BM 蛋白在上皮腔乳腺上皮细胞中的惊人作用，并强调了 Lama5 在乳腺重塑和腔分化中的功能。
