Advanced

Hyperplastic conotruncal endocardial cushions and transposition of great arteries in perlecan-null mice

Costell, M; Carmona, R; Gustafsson, Erika LU ; Gonzalez-Iriarte, M; Fässler, Reinhard LU and Munoz-Chapuli, R (2002) In Circulation Research 91(2). p.158-164
Abstract
Perlecan is a heparan-sulfate proteoglycan abundantly expressed in pericellular matrices and basement membranes during development. Inactivation of the perlecan gene in mice is lethal at two developmental stages: around E10 and around birth. We report a high incidence of malformations of the cardiac outflow tract in perlecan-deficient embryos. Complete transposition of great arteries was diagnosed in 11 out of 15 late embryos studied (73%). Three of these 11 embryos also showed. malformations of semilunar valves. Mesenchymal cells in the outflow tract were abnormally abundant in mutant embryos by E9.5, when the endocardial-mesenchymal transformation starts in wild-type embryos. At E10.5, mutant embryos lacked well-defined spiral... (More)
Perlecan is a heparan-sulfate proteoglycan abundantly expressed in pericellular matrices and basement membranes during development. Inactivation of the perlecan gene in mice is lethal at two developmental stages: around E10 and around birth. We report a high incidence of malformations of the cardiac outflow tract in perlecan-deficient embryos. Complete transposition of great arteries was diagnosed in 11 out of 15 late embryos studied (73%). Three of these 11 embryos also showed. malformations of semilunar valves. Mesenchymal cells in the outflow tract were abnormally abundant in mutant embryos by E9.5, when the endocardial-mesenchymal transformation starts in wild-type embryos. At E10.5, mutant embryos lacked well-defined spiral endocardial ridges, and the excess of mesenchymal cells obstructed sometimes the outflow tract lumen. Most of this anomalous mesenchyme expressed the smooth muscle cell-specific a-actin isoform, a marker of the neural crest in the outflow tract of the mouse. In wild-type embryos, perlecan is present in the basal surface of myocardium and endocardium, as well as surrounding presumptive neural crest cells. We suggest that the excess of mesenchyme at the earlier stages of conotruncal development precludes the formation of the spiral ridges and the rotation of the septation complex in order to achieve a concordant ventriculoarterial connection. The observed mesenchymal overpopulation might be due to an uncontrolled migration of neural crest cells, which would arrive prematurely to the heart. Thus, perlecan is involved in the control of the outflow tract mesenchymal population size, underscoring the importance of the extracellular matrix in cardiac morphogenesis. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
perlecan, outflow tract, heart, transposition of great arteries
in
Circulation Research
volume
91
issue
2
pages
158 - 164
publisher
American Heart Association
external identifiers
  • pmid:12142349
  • wos:000177122300013
  • scopus:0037178732
ISSN
0009-7330
DOI
10.1161/01.RES.0000026056.81424.DA
language
English
LU publication?
yes
id
b2a78754-ea9f-4999-84d7-bd83ff59efbe (old id 332411)
date added to LUP
2007-08-15 11:16:51
date last changed
2017-10-01 04:34:01
@article{b2a78754-ea9f-4999-84d7-bd83ff59efbe,
  abstract     = {Perlecan is a heparan-sulfate proteoglycan abundantly expressed in pericellular matrices and basement membranes during development. Inactivation of the perlecan gene in mice is lethal at two developmental stages: around E10 and around birth. We report a high incidence of malformations of the cardiac outflow tract in perlecan-deficient embryos. Complete transposition of great arteries was diagnosed in 11 out of 15 late embryos studied (73%). Three of these 11 embryos also showed. malformations of semilunar valves. Mesenchymal cells in the outflow tract were abnormally abundant in mutant embryos by E9.5, when the endocardial-mesenchymal transformation starts in wild-type embryos. At E10.5, mutant embryos lacked well-defined spiral endocardial ridges, and the excess of mesenchymal cells obstructed sometimes the outflow tract lumen. Most of this anomalous mesenchyme expressed the smooth muscle cell-specific a-actin isoform, a marker of the neural crest in the outflow tract of the mouse. In wild-type embryos, perlecan is present in the basal surface of myocardium and endocardium, as well as surrounding presumptive neural crest cells. We suggest that the excess of mesenchyme at the earlier stages of conotruncal development precludes the formation of the spiral ridges and the rotation of the septation complex in order to achieve a concordant ventriculoarterial connection. The observed mesenchymal overpopulation might be due to an uncontrolled migration of neural crest cells, which would arrive prematurely to the heart. Thus, perlecan is involved in the control of the outflow tract mesenchymal population size, underscoring the importance of the extracellular matrix in cardiac morphogenesis.},
  author       = {Costell, M and Carmona, R and Gustafsson, Erika and Gonzalez-Iriarte, M and Fässler, Reinhard and Munoz-Chapuli, R},
  issn         = {0009-7330},
  keyword      = {perlecan,outflow tract,heart,transposition of great arteries},
  language     = {eng},
  number       = {2},
  pages        = {158--164},
  publisher    = {American Heart Association},
  series       = {Circulation Research},
  title        = {Hyperplastic conotruncal endocardial cushions and transposition of great arteries in perlecan-null mice},
  url          = {http://dx.doi.org/10.1161/01.RES.0000026056.81424.DA},
  volume       = {91},
  year         = {2002},
}