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

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Date

15 juin 2021

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Périmètre
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Source

Serveur académique Lausannois

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Ce document est lié à :
info:eu-repo/semantics/altIdentifier/doi/10.15252/embj.2020107192

Ce document est lié à :
info:eu-repo/semantics/altIdentifier/pmid/33934370

Ce document est lié à :
info:eu-repo/semantics/altIdentifier/eissn/1460-2075

Ce document est lié à :
info:eu-repo/semantics/altIdentifier/urn/urn:nbn:ch:serval-BIB_4679CF9489C74

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Serveur Académique Lausannois

Organisation

Université de Lausanne et CHUV

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info:eu-repo/semantics/openAccess , CC BY-NC-ND 4.0 , https://creativecommons.org/licenses/by-nc-nd/4.0/

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Animals; Cells, Cultured; Endothelial Cells/metabolism; Female; Forkhead Transcription Factors/genetics; Forkhead Transcription Factors/metabolism; Gene Expression Profiling; Humans; Lymphangiogenesis; Lymphatic Vessels; Male; Mice, Transgenic; Morphogenesis; NFATC Transcription Factors/genetics; NFATC Transcription Factors/metabolism; Repressor Proteins/genetics; Repressor Proteins/metabolism; Stress, Mechanical; lymphatic vessel; shear stress; valve

Sujets proches En

Speech--Transcription Language and languages--Transcription Transcribing Transcribing

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M.N. Hernández Vásquez et al., « Transcription factor FOXP2 is a flow-induced regulator of collecting lymphatic vessels. », Serveur académique Lausannois, ID : 10.15252/embj.2020107192

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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 T2 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.

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