Transcription factor FOXP2 is a flow-induced regulator of collecting lymphatic vessels
| Autor: | Tatiana V. Petrova, Ying Sun, Maria H. Ulvmar, Alejandra González-Loyola, Ioannis Kritikos, Taija Makinen, Liqun He, Cornelia Halin, Magda Hernandez Vasquez |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Male
Vascular Biology & Angiogenesis Cell- och molekylärbiologi Regulator Chromatin Epigenetics Genomics & Functional Genomics 0302 clinical medicine Transcriptional regulation Morphogenesis Lymphangiogenesis Animals Cells Cultured Endothelial Cells/metabolism Female Forkhead Transcription Factors/genetics Forkhead Transcription Factors/metabolism Gene Expression Profiling Humans Lymphatic Vessels Mice Transgenic NFATC Transcription Factors/genetics NFATC Transcription Factors/metabolism Repressor Proteins/genetics Repressor Proteins/metabolism Stress Mechanical lymphatic vessel shear stress valve 0303 health sciences biology General Neuroscience Forkhead Transcription Factors Articles 3. Good health Cell biology Endothelial stem cell Lymphatic Endothelium Lymphatic system medicine.anatomical_structure FOXC2 government.form_of_government General Biochemistry Genetics and Molecular Biology Article 03 medical and health sciences Lymphatic vessel medicine Molecular Biology Transcription factor 030304 developmental biology General Immunology and Microbiology NFATC Transcription Factors Endothelial Cells Repressor Proteins biology.protein government Development & Differentiation 030217 neurology & neurosurgery Cell and Molecular Biology |
| Zdroj: | The EMBO journal, vol. 40, no. 12, pp. e107192 The EMBO Journal |
| Popis: | 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‐CreERT2 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. Speech‐linked FOXP2 is a specific marker of collecting lymphatic vessels that regulates lymphatic vessel and valve morphogenesis downstream of flow‐responsive transcriptional regulator FOXC2. |
| Databáze: | OpenAIRE |
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