Matrix stiffness controls lymphatic vessel formation through regulation of a GATA2-dependent transcriptional program

• DOI: 10.1038/s41467-018-03959-6
• Publication Date: 2018-04-11T10:01:26Z
• Authors: Maike Frye; Andrea Taddei; Cathrin Dierkes; Ines Martinez-Corral; Matthew Fielden; Henrik Ortsäter; Jan Kazenwadel; Dinis P. Calado; Pia Ostergaard; Marjo Salminen; Liqun He; Natasha L. Harvey; Friedemann Kiefer; Taija Mäkinen
• Keywords: Lymphatic Endothelium; Lymphangiogenesis; Lymphatic vessel; Cell fate determination; Matrix (chemical analysis)

Tissue and vessel wall stiffening alters endothelial cell properties contributes to vascular dysfunction. However, whether extracellular matrix (ECM) stiffness impacts development is not known. Here we show that controls lymphatic morphogenesis. Atomic force microscopy measurements in mouse embryos reveal venous (LEC) progenitors experience a decrease substrate upon migration out of the cardinal vein, which induces GATA2-dependent transcriptional program required form first vessels. Transcriptome analysis shows LECs grown on soft exhibit increased GATA2 expression upregulation genes involved lymphangiogenesis, including VEGFR3. Analyses models demonstrate cell-autonomous function regulating LEC responsiveness VEGF-C controlling sprouting vivo. Our study thus uncovers mechanism by ECM dictates migratory behavior during early development.