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Transcription factor FOXP2 is a flow‐induced regulator of collecting lymphatic vessels
Author(s) -
Hernández Vásquez Magda N,
Ulvmar Maria H,
GonzálezLoyola Alejandra,
Kritikos Ioannis,
Sun Ying,
He Liqun,
Halin Cornelia,
Petrova Tatiana V,
Mäkinen Taija
Publication year - 2021
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.2020107192
Subject(s) - biology , regulator , transcription factor , lymphatic system , transcription (linguistics) , negative regulator , microbiology and biotechnology , genetics , gene , immunology , linguistics , philosophy
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.