Abrogation of TGF-beta signalling in TAGLN expressing cells recapitulates Pentalogy of Cantrell in the mouse

B Aldeiri, U Roostalu, A Albertini, J Behnsen, J Wong, A Morabito, G Cossu

Research output: Contribution to journalArticle

Abstract

Pentalogy of Cantrell (PC) is a rare multi-organ congenital anomaly that impedes ventral body wall closure and results in diaphragmatic hernia, intra- and pericardial defects. The underlying cellular and molecular changes that lead to these severe developmental defects have remained unknown largely due to the lack of representative animal models. Here we provide in depth characterization of a mouse model with conditional ablation of TGFβRII in Transgelin (Tagln) expressing cells. We show that Tagln is transiently expressed in a variety of cells that participate in the embryonic development and patterning of ventral structures. Genetic ablation of TGFβRII in these cells leads to ventral midline closure defect, diaphragmatic hernia, dilated cardiac outflow tract and aberrant cardiac septation, providing a reliable model to study the morphological changes leading to PC. We show that myogenisis in the diaphragm is independent of TGFβ and the diaphragmatic hernia arises from fibroblast-specific migration defect. In the dorsal body wall Tagln expression is initiated after the closure process, revealing a remarkable difference between ventral and dorsal body walls development. Our study demonstrates the use of micro-CT scanning to obtain a 3-dimensional high-resolution overview of embryonic anomalies and provides the first mechanistic insight into the development of PC. © 2018 The Author(s).
Original languageEnglish
Article number3658
JournalScientific Reports
Volume8
Issue number5
DOIs
Publication statusPublished - 2018

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Pentalogy of Cantrell
Diaphragmatic Hernia
Transforming Growth Factor beta
Diaphragm
Embryonic Development
Animal Models
Fibroblasts
transgelin

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Abrogation of TGF-beta signalling in TAGLN expressing cells recapitulates Pentalogy of Cantrell in the mouse. / Aldeiri, B; Roostalu, U; Albertini, A; Behnsen, J; Wong, J; Morabito, A; Cossu, G.

In: Scientific Reports, Vol. 8, No. 5, 3658, 2018.

Research output: Contribution to journalArticle

Aldeiri, B ; Roostalu, U ; Albertini, A ; Behnsen, J ; Wong, J ; Morabito, A ; Cossu, G. / Abrogation of TGF-beta signalling in TAGLN expressing cells recapitulates Pentalogy of Cantrell in the mouse. In: Scientific Reports. 2018 ; Vol. 8, No. 5.
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abstract = "Pentalogy of Cantrell (PC) is a rare multi-organ congenital anomaly that impedes ventral body wall closure and results in diaphragmatic hernia, intra- and pericardial defects. The underlying cellular and molecular changes that lead to these severe developmental defects have remained unknown largely due to the lack of representative animal models. Here we provide in depth characterization of a mouse model with conditional ablation of TGFβRII in Transgelin (Tagln) expressing cells. We show that Tagln is transiently expressed in a variety of cells that participate in the embryonic development and patterning of ventral structures. Genetic ablation of TGFβRII in these cells leads to ventral midline closure defect, diaphragmatic hernia, dilated cardiac outflow tract and aberrant cardiac septation, providing a reliable model to study the morphological changes leading to PC. We show that myogenisis in the diaphragm is independent of TGFβ and the diaphragmatic hernia arises from fibroblast-specific migration defect. In the dorsal body wall Tagln expression is initiated after the closure process, revealing a remarkable difference between ventral and dorsal body walls development. Our study demonstrates the use of micro-CT scanning to obtain a 3-dimensional high-resolution overview of embryonic anomalies and provides the first mechanistic insight into the development of PC. {\circledC} 2018 The Author(s).",
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AU - Aldeiri, B

AU - Roostalu, U

AU - Albertini, A

AU - Behnsen, J

AU - Wong, J

AU - Morabito, A

AU - Cossu, G

PY - 2018

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AB - Pentalogy of Cantrell (PC) is a rare multi-organ congenital anomaly that impedes ventral body wall closure and results in diaphragmatic hernia, intra- and pericardial defects. The underlying cellular and molecular changes that lead to these severe developmental defects have remained unknown largely due to the lack of representative animal models. Here we provide in depth characterization of a mouse model with conditional ablation of TGFβRII in Transgelin (Tagln) expressing cells. We show that Tagln is transiently expressed in a variety of cells that participate in the embryonic development and patterning of ventral structures. Genetic ablation of TGFβRII in these cells leads to ventral midline closure defect, diaphragmatic hernia, dilated cardiac outflow tract and aberrant cardiac septation, providing a reliable model to study the morphological changes leading to PC. We show that myogenisis in the diaphragm is independent of TGFβ and the diaphragmatic hernia arises from fibroblast-specific migration defect. In the dorsal body wall Tagln expression is initiated after the closure process, revealing a remarkable difference between ventral and dorsal body walls development. Our study demonstrates the use of micro-CT scanning to obtain a 3-dimensional high-resolution overview of embryonic anomalies and provides the first mechanistic insight into the development of PC. © 2018 The Author(s).

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