Transforming growth factor β-SMAD2 signaling regulates aortic arch innervation and development

Daniel G M Molin, Robert E. Poelmann, Marco C. DeRuiter, Mohamad Azhar, Thomas C Doetschman, Adriana C. Gittenberger-de Groot

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

Aortic arch interruptions in humans and animal models are mainly caused by aberrant development of the fourth pharyngeal arch artery. Little is known about the maturation of this vessel during normal and abnormal development, which is the subject of this study. Tgfβ2 knockout mice that present with fourth artery defects have been associated with defective neural crest cell migration. In this study, we concentrated on pharyngeal arch artery development during developmental days 12.5 to 18.5, focusing on neural crest cell migration using a Wnt1-Cre by R26R neural crest cell reporter mouse. Fourth arch artery maturation was studied with antibodies directed against smooth muscle α-actin and neural NCAM-1 and RMO-270. For diminished transforming growth factor β (TGF-β) signaling, SMAD2 and fibronectin have been analyzed. Neural crest migration and differentiation into smooth muscle cells is unaltered in mutants, regardless of the cardiovascular defect found; however, innervation of the fourth arch artery is affected. Absent staining for nuclear SMAD2, NCAM-1, and RMO-270 in the fourth artery in mutant coincides with severe defects of this segment. Likewise, fibronectin expression is diminished in these cases. From these data we conclude the following: (1) neural crest cell migration is not a common denominator in cardiovascular defects of Tgfβ2-/- mice; (2) fourth arch artery maturation is a complex process involving innervation; and (3) TGF-β2 depletion diminishes SMAD2-signaling in the fourth arch artery and coincides with reduced vascular NCAM-1 expression and neural innervation of this artery. We hypothesize that disturbed maturation of the fourth pharyngeal arch artery, and especially abrogated vascular innervation, will result in fourth arch interruptions.

Original languageEnglish (US)
Pages (from-to)1109-1117
Number of pages9
JournalCirculation Research
Volume95
Issue number11
DOIs
StatePublished - Nov 26 2004
Externally publishedYes

Fingerprint

Transforming Growth Factors
Thoracic Aorta
Arteries
Neural Crest
Branchial Region
Neural Cell Adhesion Molecules
Cell Movement
Fibronectins
Blood Vessels
Knockout Mice
Smooth Muscle Myocytes
Smooth Muscle
Actins
Animal Models
Staining and Labeling
Antibodies

Keywords

  • Embryo
  • NCAM
  • Neural crest
  • SMAD
  • Vascular innervation

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Molin, D. G. M., Poelmann, R. E., DeRuiter, M. C., Azhar, M., Doetschman, T. C., & Gittenberger-de Groot, A. C. (2004). Transforming growth factor β-SMAD2 signaling regulates aortic arch innervation and development. Circulation Research, 95(11), 1109-1117. https://doi.org/10.1161/01.RES.0000150047.16909.ab

Transforming growth factor β-SMAD2 signaling regulates aortic arch innervation and development. / Molin, Daniel G M; Poelmann, Robert E.; DeRuiter, Marco C.; Azhar, Mohamad; Doetschman, Thomas C; Gittenberger-de Groot, Adriana C.

In: Circulation Research, Vol. 95, No. 11, 26.11.2004, p. 1109-1117.

Research output: Contribution to journalArticle

Molin, DGM, Poelmann, RE, DeRuiter, MC, Azhar, M, Doetschman, TC & Gittenberger-de Groot, AC 2004, 'Transforming growth factor β-SMAD2 signaling regulates aortic arch innervation and development', Circulation Research, vol. 95, no. 11, pp. 1109-1117. https://doi.org/10.1161/01.RES.0000150047.16909.ab
Molin, Daniel G M ; Poelmann, Robert E. ; DeRuiter, Marco C. ; Azhar, Mohamad ; Doetschman, Thomas C ; Gittenberger-de Groot, Adriana C. / Transforming growth factor β-SMAD2 signaling regulates aortic arch innervation and development. In: Circulation Research. 2004 ; Vol. 95, No. 11. pp. 1109-1117.
@article{40bcaac2f198466897f155175e3dd462,
title = "Transforming growth factor β-SMAD2 signaling regulates aortic arch innervation and development",
abstract = "Aortic arch interruptions in humans and animal models are mainly caused by aberrant development of the fourth pharyngeal arch artery. Little is known about the maturation of this vessel during normal and abnormal development, which is the subject of this study. Tgfβ2 knockout mice that present with fourth artery defects have been associated with defective neural crest cell migration. In this study, we concentrated on pharyngeal arch artery development during developmental days 12.5 to 18.5, focusing on neural crest cell migration using a Wnt1-Cre by R26R neural crest cell reporter mouse. Fourth arch artery maturation was studied with antibodies directed against smooth muscle α-actin and neural NCAM-1 and RMO-270. For diminished transforming growth factor β (TGF-β) signaling, SMAD2 and fibronectin have been analyzed. Neural crest migration and differentiation into smooth muscle cells is unaltered in mutants, regardless of the cardiovascular defect found; however, innervation of the fourth arch artery is affected. Absent staining for nuclear SMAD2, NCAM-1, and RMO-270 in the fourth artery in mutant coincides with severe defects of this segment. Likewise, fibronectin expression is diminished in these cases. From these data we conclude the following: (1) neural crest cell migration is not a common denominator in cardiovascular defects of Tgfβ2-/- mice; (2) fourth arch artery maturation is a complex process involving innervation; and (3) TGF-β2 depletion diminishes SMAD2-signaling in the fourth arch artery and coincides with reduced vascular NCAM-1 expression and neural innervation of this artery. We hypothesize that disturbed maturation of the fourth pharyngeal arch artery, and especially abrogated vascular innervation, will result in fourth arch interruptions.",
keywords = "Embryo, NCAM, Neural crest, SMAD, Vascular innervation",
author = "Molin, {Daniel G M} and Poelmann, {Robert E.} and DeRuiter, {Marco C.} and Mohamad Azhar and Doetschman, {Thomas C} and {Gittenberger-de Groot}, {Adriana C.}",
year = "2004",
month = "11",
day = "26",
doi = "10.1161/01.RES.0000150047.16909.ab",
language = "English (US)",
volume = "95",
pages = "1109--1117",
journal = "Circulation Research",
issn = "0009-7330",
publisher = "Lippincott Williams and Wilkins",
number = "11",

}

TY - JOUR

T1 - Transforming growth factor β-SMAD2 signaling regulates aortic arch innervation and development

AU - Molin, Daniel G M

AU - Poelmann, Robert E.

AU - DeRuiter, Marco C.

AU - Azhar, Mohamad

AU - Doetschman, Thomas C

AU - Gittenberger-de Groot, Adriana C.

PY - 2004/11/26

Y1 - 2004/11/26

N2 - Aortic arch interruptions in humans and animal models are mainly caused by aberrant development of the fourth pharyngeal arch artery. Little is known about the maturation of this vessel during normal and abnormal development, which is the subject of this study. Tgfβ2 knockout mice that present with fourth artery defects have been associated with defective neural crest cell migration. In this study, we concentrated on pharyngeal arch artery development during developmental days 12.5 to 18.5, focusing on neural crest cell migration using a Wnt1-Cre by R26R neural crest cell reporter mouse. Fourth arch artery maturation was studied with antibodies directed against smooth muscle α-actin and neural NCAM-1 and RMO-270. For diminished transforming growth factor β (TGF-β) signaling, SMAD2 and fibronectin have been analyzed. Neural crest migration and differentiation into smooth muscle cells is unaltered in mutants, regardless of the cardiovascular defect found; however, innervation of the fourth arch artery is affected. Absent staining for nuclear SMAD2, NCAM-1, and RMO-270 in the fourth artery in mutant coincides with severe defects of this segment. Likewise, fibronectin expression is diminished in these cases. From these data we conclude the following: (1) neural crest cell migration is not a common denominator in cardiovascular defects of Tgfβ2-/- mice; (2) fourth arch artery maturation is a complex process involving innervation; and (3) TGF-β2 depletion diminishes SMAD2-signaling in the fourth arch artery and coincides with reduced vascular NCAM-1 expression and neural innervation of this artery. We hypothesize that disturbed maturation of the fourth pharyngeal arch artery, and especially abrogated vascular innervation, will result in fourth arch interruptions.

AB - Aortic arch interruptions in humans and animal models are mainly caused by aberrant development of the fourth pharyngeal arch artery. Little is known about the maturation of this vessel during normal and abnormal development, which is the subject of this study. Tgfβ2 knockout mice that present with fourth artery defects have been associated with defective neural crest cell migration. In this study, we concentrated on pharyngeal arch artery development during developmental days 12.5 to 18.5, focusing on neural crest cell migration using a Wnt1-Cre by R26R neural crest cell reporter mouse. Fourth arch artery maturation was studied with antibodies directed against smooth muscle α-actin and neural NCAM-1 and RMO-270. For diminished transforming growth factor β (TGF-β) signaling, SMAD2 and fibronectin have been analyzed. Neural crest migration and differentiation into smooth muscle cells is unaltered in mutants, regardless of the cardiovascular defect found; however, innervation of the fourth arch artery is affected. Absent staining for nuclear SMAD2, NCAM-1, and RMO-270 in the fourth artery in mutant coincides with severe defects of this segment. Likewise, fibronectin expression is diminished in these cases. From these data we conclude the following: (1) neural crest cell migration is not a common denominator in cardiovascular defects of Tgfβ2-/- mice; (2) fourth arch artery maturation is a complex process involving innervation; and (3) TGF-β2 depletion diminishes SMAD2-signaling in the fourth arch artery and coincides with reduced vascular NCAM-1 expression and neural innervation of this artery. We hypothesize that disturbed maturation of the fourth pharyngeal arch artery, and especially abrogated vascular innervation, will result in fourth arch interruptions.

KW - Embryo

KW - NCAM

KW - Neural crest

KW - SMAD

KW - Vascular innervation

UR - http://www.scopus.com/inward/record.url?scp=9344269912&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=9344269912&partnerID=8YFLogxK

U2 - 10.1161/01.RES.0000150047.16909.ab

DO - 10.1161/01.RES.0000150047.16909.ab

M3 - Article

C2 - 15528466

AN - SCOPUS:9344269912

VL - 95

SP - 1109

EP - 1117

JO - Circulation Research

JF - Circulation Research

SN - 0009-7330

IS - 11

ER -