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转录因子 Sox10 是小鼠乳腺分支形态发生和内陷的必需决定因素。

The transcription factor Sox10 is an essential determinant of branching morphogenesis and involution in the mouse mammary gland.

机构信息

Institut für Biochemie, Emil-Fischer-Zentrum, Friedrich-Alexander-Universität Erlangen-Nürnberg, Fahrstrasse 17, 91054, Erlangen, Germany.

Zahnklinik 3 - Kieferorthopädie, Universitätsklinikum Erlangen, FAU Erlangen-Nürnberg, Glückstrasse 6, 91054, Erlangen, Germany.

出版信息

Sci Rep. 2020 Oct 20;10(1):17807. doi: 10.1038/s41598-020-74664-y.

DOI:10.1038/s41598-020-74664-y
PMID:33082503
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7575560/
Abstract

The high mobility group-domain containing transcription factor Sox10 is an essential regulator of developmental processes and homeostasis in the neural crest, several neural crest-derived lineages and myelinating glia. Recent studies have also implicated Sox10 as an important factor in mammary stem and precursor cells. Here we employ a series of mouse mutants with constitutive and conditional Sox10 deficiencies to show that Sox10 has multiple functions in the developing mammary gland. While there is no indication for a requirement of Sox10 in the specification of the mammary placode or descending mammary bud, it is essential for both the prenatal hormone-independent as well as the pubertal hormone-dependent branching of the mammary epithelium and for proper alveologenesis during pregnancy. It furthermore acts in a dosage-dependent manner. Sox10 also plays a role during the involution process at the end of the lactation period. Whereas its effect on epithelial branching and alveologenesis are likely causally related to its function in mammary stem and precursor cells, this is not the case for its function during involution where Sox10 seems to work at least in part through regulation of the miR-424(322)/503 cluster.

摘要

高迁移率族蛋白结构域转录因子 Sox10 是神经嵴、几个神经嵴衍生谱系和髓鞘形成胶质细胞发育过程和内稳态的必需调节因子。最近的研究还表明 Sox10 是乳腺干细胞和前体细胞中的一个重要因素。在这里，我们利用一系列 Sox10 组成型和条件性缺失的小鼠突变体，表明 Sox10 在乳腺发育过程中具有多种功能。虽然 Sox10 对于乳腺嵴的特化或乳腺芽的下降没有表明是必需的，但它对于乳腺上皮的产前激素非依赖性和青春期激素依赖性分支以及妊娠期间的适当肺泡发生都是必需的。它还以剂量依赖的方式发挥作用。Sox10 在哺乳期结束时的 involution 过程中也发挥作用。尽管它对上皮分支和肺泡发生的影响可能与其在乳腺干细胞和前体细胞中的功能有因果关系，但在 involution 期间并非如此，在 involution 期间，Sox10 似乎至少部分通过调节 miR-424(322)/503 簇发挥作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d858/7575560/e915cdfe74e1/41598_2020_74664_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d858/7575560/01eb933133f5/41598_2020_74664_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d858/7575560/a3d86edd226b/41598_2020_74664_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d858/7575560/01aa9c7ff2e8/41598_2020_74664_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d858/7575560/71aa38a72d1e/41598_2020_74664_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d858/7575560/858e41847b82/41598_2020_74664_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d858/7575560/e915cdfe74e1/41598_2020_74664_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d858/7575560/01eb933133f5/41598_2020_74664_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d858/7575560/bc8f96f65ecb/41598_2020_74664_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d858/7575560/19237114e832/41598_2020_74664_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d858/7575560/a3d86edd226b/41598_2020_74664_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d858/7575560/01aa9c7ff2e8/41598_2020_74664_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d858/7575560/71aa38a72d1e/41598_2020_74664_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d858/7575560/858e41847b82/41598_2020_74664_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d858/7575560/e915cdfe74e1/41598_2020_74664_Fig8_HTML.jpg

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