Transcription factor FOXP2 is a flow-induced regulator of collecting lymphatic vessels.

Details

Serval ID
serval:BIB_4679CF9489C7
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Transcription factor FOXP2 is a flow-induced regulator of collecting lymphatic vessels.
Journal
The EMBO journal
Author(s)
Hernández Vásquez M.N., Ulvmar M.H., González-Loyola A., Kritikos I., Sun Y., He L., Halin C., Petrova T.V., Mäkinen T.
ISSN
1460-2075 (Electronic)
ISSN-L
0261-4189
Publication state
Published
Issued date
15/06/2021
Peer-reviewed
Oui
Volume
40
Number
12
Pages
e107192
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
The lymphatic system is composed of a hierarchical network of fluid absorbing lymphatic capillaries and transporting collecting vessels. Despite distinct functions and morphologies, molecular mechanisms that regulate the identity of the different vessel types are poorly understood. Through transcriptional analysis of murine dermal lymphatic endothelial cells (LECs), we identified Foxp2, a member of the FOXP family of transcription factors implicated in speech development, as a collecting vessel signature gene. FOXP2 expression was induced after initiation of lymph flow in vivo and upon shear stress on primary LECs in vitro. Loss of FOXC2, the major flow-responsive transcriptional regulator of lymphatic valve formation, abolished FOXP2 induction in vitro and in vivo. Genetic deletion of Foxp2 in mice using the endothelial-specific Tie2-Cre or the tamoxifen-inducible LEC-specific Prox1-CreER <sup>T2</sup> line resulted in enlarged collecting vessels and defective valves characterized by loss of NFATc1 activity. Our results identify FOXP2 as a new flow-induced transcriptional regulator of collecting lymphatic vessel morphogenesis and highlight the existence of unique transcription factor codes in the establishment of vessel-type-specific endothelial cell identities.
Keywords
lymphatic vessel, shear stress, valve
Pubmed
Web of science
Open Access
Yes
Create date
19/05/2021 13:18
Last modification date
27/06/2021 6:37
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