Formation of the venous pole of the heart from an Nkx2-5-negative precursor population requires Tbx18.

The venous pole of the mammalian heart is a structurally and electrically complex region, yet the lineage and molecular mechanisms underlying its formation have remained largely unexplored. In contrast to classical studies that attribute the origin of the myocardial sinus horns to the embryonic veno...

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Main Authors: Christoffels, V, Mommersteeg, M, Trowe, M, Prall, O, de Gier-de Vries, C, Soufan, A, Bussen, M, Schuster-Gossler, K, Harvey, R, Moorman, A, Kispert, A
Format: Journal article
Language:English
Published: 2006
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author Christoffels, V
Mommersteeg, M
Trowe, M
Prall, O
de Gier-de Vries, C
Soufan, A
Bussen, M
Schuster-Gossler, K
Harvey, R
Moorman, A
Kispert, A
author_facet Christoffels, V
Mommersteeg, M
Trowe, M
Prall, O
de Gier-de Vries, C
Soufan, A
Bussen, M
Schuster-Gossler, K
Harvey, R
Moorman, A
Kispert, A
author_sort Christoffels, V
collection OXFORD
description The venous pole of the mammalian heart is a structurally and electrically complex region, yet the lineage and molecular mechanisms underlying its formation have remained largely unexplored. In contrast to classical studies that attribute the origin of the myocardial sinus horns to the embryonic venous pole, we find that the sinus horns form only after heart looping by differentiation of mesenchymal cells of the septum transversum region into myocardium. The myocardial sinus horns and their mesenchymal precursor cells never express Nkx2-5, a transcription factor critical for heart development. In addition, lineage studies show that the sinus horns do not derive from cells previously positive for Nkx2-5. In contrast, the sinus horns express the T-box transcription factor gene Tbx18. Mice deficient for Tbx18 fail to form sinus horns from the pericardial mesenchyme and have defective caval veins, whereas the pulmonary vein and atrial structures are unaffected. Our studies define a novel heart precursor population that contributes exclusively to the myocardium surrounding the sinus horns or systemic venous tributaries of the developing heart, which are a source of congenital malformation and cardiac arrhythmias.
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spelling oxford-uuid:2125f3ff-4591-4992-ad8a-ef49ddd428ed2022-03-26T11:31:41ZFormation of the venous pole of the heart from an Nkx2-5-negative precursor population requires Tbx18.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:2125f3ff-4591-4992-ad8a-ef49ddd428edEnglishSymplectic Elements at Oxford2006Christoffels, VMommersteeg, MTrowe, MPrall, Ode Gier-de Vries, CSoufan, ABussen, MSchuster-Gossler, KHarvey, RMoorman, AKispert, AThe venous pole of the mammalian heart is a structurally and electrically complex region, yet the lineage and molecular mechanisms underlying its formation have remained largely unexplored. In contrast to classical studies that attribute the origin of the myocardial sinus horns to the embryonic venous pole, we find that the sinus horns form only after heart looping by differentiation of mesenchymal cells of the septum transversum region into myocardium. The myocardial sinus horns and their mesenchymal precursor cells never express Nkx2-5, a transcription factor critical for heart development. In addition, lineage studies show that the sinus horns do not derive from cells previously positive for Nkx2-5. In contrast, the sinus horns express the T-box transcription factor gene Tbx18. Mice deficient for Tbx18 fail to form sinus horns from the pericardial mesenchyme and have defective caval veins, whereas the pulmonary vein and atrial structures are unaffected. Our studies define a novel heart precursor population that contributes exclusively to the myocardium surrounding the sinus horns or systemic venous tributaries of the developing heart, which are a source of congenital malformation and cardiac arrhythmias.
spellingShingle Christoffels, V
Mommersteeg, M
Trowe, M
Prall, O
de Gier-de Vries, C
Soufan, A
Bussen, M
Schuster-Gossler, K
Harvey, R
Moorman, A
Kispert, A
Formation of the venous pole of the heart from an Nkx2-5-negative precursor population requires Tbx18.
title Formation of the venous pole of the heart from an Nkx2-5-negative precursor population requires Tbx18.
title_full Formation of the venous pole of the heart from an Nkx2-5-negative precursor population requires Tbx18.
title_fullStr Formation of the venous pole of the heart from an Nkx2-5-negative precursor population requires Tbx18.
title_full_unstemmed Formation of the venous pole of the heart from an Nkx2-5-negative precursor population requires Tbx18.
title_short Formation of the venous pole of the heart from an Nkx2-5-negative precursor population requires Tbx18.
title_sort formation of the venous pole of the heart from an nkx2 5 negative precursor population requires tbx18
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