An EGFP-Col4a2 Mouse Model Reveals Basement Membrane Dynamics Underlying Hair Follicle Morphogenesis

Overview

Journal J Cell Biol

Specialty Cell Biology

Date 2024 Dec 10

PMID 39656438

Authors

Duligengaowa Wuergezhen

Eleonore Gindroz

Ritsuko Morita

Kei Hashimoto

Takaya Abe

Hiroshi Kiyonari

Hironobu Fujiwara

Affiliations

Soon will be listed here.

Abstract

Precisely controlled remodeling of the basement membrane (BM) is crucial for morphogenesis, but its molecular and tissue-level dynamics, underlying mechanisms, and functional significance in mammals remain largely unknown due to limited visualization tools. We developed mouse lines in which the endogenous collagen IV gene (Col4a2) was fused with a fluorescent tag. Through live imaging of developing hair follicles, we reveal a spatial gradient in the turnover rate of COL4A2 that is closely coupled with both the BM expansion rate and the proliferation rate of epithelial progenitors. Epithelial progenitors are displaced with directionally expanding BMs but do not actively migrate on stationary BM. The addition of a matrix metalloproteinase inhibitor delays COL4A2 turnover, restrains BM expansion, and increases perpendicular divisions of epithelial progenitors, altering hair follicle morphology. Our findings highlight the spatially distinct dynamics of BM and their key roles in orchestrating progenitor cell behavior and organ shape during development.

References

Crest J, Diz-Munoz A, Chen D, Fletcher D, Bilder D . Organ sculpting by patterned extracellular matrix stiffness. Elife. 2017; 6. PMC: 5503509. DOI: 10.7554/eLife.24958. View

Ramos-Lewis W, LaFever K, Page-McCaw A . A scar-like lesion is apparent in basement membrane after wound repair in vivo. Matrix Biol. 2018; 74:101-120. PMC: 6250587. DOI: 10.1016/j.matbio.2018.07.004. View

Gudipaty S, Lindblom J, Loftus P, Redd M, Edes K, Davey C . Mechanical stretch triggers rapid epithelial cell division through Piezo1. Nature. 2017; 543(7643):118-121. PMC: 5334365. DOI: 10.1038/nature21407. View

Bahr J, Li X, Feinberg T, Jiang L, Weiss S . Divergent regulation of basement membrane trafficking by human macrophages and cancer cells. Nat Commun. 2022; 13(1):6409. PMC: 9613642. DOI: 10.1038/s41467-022-34087-x. View

Habuchi S, Tsutsui H, Kochaniak A, Miyawaki A, van Oijen A . mKikGR, a monomeric photoswitchable fluorescent protein. PLoS One. 2008; 3(12):e3944. PMC: 2592542. DOI: 10.1371/journal.pone.0003944. View

Morin X, Daneman R, Zavortink M, Chia W . A protein trap strategy to detect GFP-tagged proteins expressed from their endogenous loci in Drosophila. Proc Natl Acad Sci U S A. 2001; 98(26):15050-5. PMC: 64981. DOI: 10.1073/pnas.261408198. View

Anazco C, Lopez-Jimenez A, Rafi M, Vega-Montoto L, Zhang M, Hudson B . Lysyl Oxidase-like-2 Cross-links Collagen IV of Glomerular Basement Membrane. J Biol Chem. 2016; 291(50):25999-26012. PMC: 5207071. DOI: 10.1074/jbc.M116.738856. View

Keeley D, Hastie E, Jayadev R, Kelley L, Chi Q, Payne S . Comprehensive Endogenous Tagging of Basement Membrane Components Reveals Dynamic Movement within the Matrix Scaffolding. Dev Cell. 2020; 54(1):60-74.e7. PMC: 7394237. DOI: 10.1016/j.devcel.2020.05.022. View

Abe T, Inoue K, Furuta Y, Kiyonari H . Pronuclear Microinjection during S-Phase Increases the Efficiency of CRISPR-Cas9-Assisted Knockin of Large DNA Donors in Mouse Zygotes. Cell Rep. 2020; 31(7):107653. DOI: 10.1016/j.celrep.2020.107653. View

10.

Baena-Lopez L, Baonza A, Garcia-Bellido A . The orientation of cell divisions determines the shape of Drosophila organs. Curr Biol. 2005; 15(18):1640-4. DOI: 10.1016/j.cub.2005.07.062. View

11.

Nestor-Bergmann A, Stooke-Vaughan G, Goddard G, Starborg T, Jensen O, Woolner S . Decoupling the Roles of Cell Shape and Mechanical Stress in Orienting and Cueing Epithelial Mitosis. Cell Rep. 2019; 26(8):2088-2100.e4. PMC: 6381790. DOI: 10.1016/j.celrep.2019.01.102. View

12.

Topfer U, Guerra Santillan K, Fischer-Friedrich E, Dahmann C . Distinct contributions of ECM proteins to basement membrane mechanical properties in Drosophila. Development. 2022; 149(10). DOI: 10.1242/dev.200456. View

13.

Adameyko I, Lallemend F, Aquino J, Pereira J, Topilko P, Muller T . Schwann cell precursors from nerve innervation are a cellular origin of melanocytes in skin. Cell. 2009; 139(2):366-79. DOI: 10.1016/j.cell.2009.07.049. View

14.

Box K, Joyce B, Devenport D . Epithelial geometry regulates spindle orientation and progenitor fate during formation of the mammalian epidermis. Elife. 2019; 8. PMC: 6592681. DOI: 10.7554/eLife.47102. View

15.

Zamir E, Rongish B, Little C . The ECM moves during primitive streak formation--computation of ECM versus cellular motion. PLoS Biol. 2008; 6(10):e247. PMC: 2567004. DOI: 10.1371/journal.pbio.0060247. View

16.

Tsutsui K, Machida H, Nakagawa A, Ahn K, Morita R, Sekiguchi K . Mapping the molecular and structural specialization of the skin basement membrane for inter-tissue interactions. Nat Commun. 2021; 12(1):2577. PMC: 8110968. DOI: 10.1038/s41467-021-22881-y. View

17.

Fidler A, Boudko S, Rokas A, Hudson B . The triple helix of collagens - an ancient protein structure that enabled animal multicellularity and tissue evolution. J Cell Sci. 2018; 131(7). PMC: 5963836. DOI: 10.1242/jcs.203950. View

18.

Ramos-Lewis W, Page-McCaw A . Basement membrane mechanics shape development: Lessons from the fly. Matrix Biol. 2018; 75-76:72-81. PMC: 6185827. DOI: 10.1016/j.matbio.2018.04.004. View

19.

Serna-Morales E, Sanchez-Sanchez B, Marcotti S, Nichols A, Bhargava A, Dragu A . Extracellular matrix assembly stress initiates Drosophila central nervous system morphogenesis. Dev Cell. 2023; 58(10):825-835.e6. PMC: 10390342. DOI: 10.1016/j.devcel.2023.03.019. View

20.

Manning L, Peifer M . Getting into shape: tissue tension drives oriented cell divisions during organogenesis. EMBO J. 2019; 38(3). PMC: 6356058. DOI: 10.15252/embj.2018101246. View