Multiple cardiovascular defects caused by the absence of alternatively spliced segments of fibronectin

Sophie Astrof, Denise Crowley, Richard O. Hynes

Research output: Contribution to journalArticle

77 Citations (Scopus)

Abstract

Alternatively spliced variants of fibronectin (FN) containing exons EIIIA and EIIIB are expressed around newly forming vessels in development and disease but are downregulated in mature vasculature. The sequences and patterns of expression of these splice variants are highly conserved among vertebrates, suggestive of their biological importance; however the functions of EIIIA and EIIIB-containing FNs are unknown. To understand the role(s) of these splice variants, we deleted both EIIIA and EIIIB exons from the FN gene and observed embryonic lethality with incomplete penetrance by embryonic day 10.5. Deletion of both EIIIA and EIIIB exons did not affect synthesis or cell surface deposition of FN, indicating that embryonic lethality was due specifically to the absence of EIIIA and EIIIB exons from FN. EIIIA/EIIIB double-null embryos displayed multiple embryonic cardiovascular defects, including vascular hemorrhage, failure of remodeling embryonic and yolk sac vasculature, defective placental angiogenesis and heart defects. In addition, we observed defects in coverage and association with dorsal aortae of alpha-smooth-muscle-actin-positive cells. Our studies indicate that the presence or absence of EIIIA and EIIIB exons alters the function of FN and demonstrate the requirement for these alternatively spliced exons in cardiovascular development.

Original languageEnglish (US)
Pages (from-to)11-24
Number of pages14
JournalDevelopmental biology
Volume311
Issue number1
DOIs
StatePublished - Nov 1 2007
Externally publishedYes

Fingerprint

Fibronectins
Exons
Yolk Sac
Penetrance
Smooth Muscle
Blood Vessels
Aorta
Vertebrates
Actins
Down-Regulation
Embryonic Structures
Hemorrhage
Genes

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology
  • Developmental Biology

Cite this

@article{672247674a4746699cb121e30842279e,
title = "Multiple cardiovascular defects caused by the absence of alternatively spliced segments of fibronectin",
abstract = "Alternatively spliced variants of fibronectin (FN) containing exons EIIIA and EIIIB are expressed around newly forming vessels in development and disease but are downregulated in mature vasculature. The sequences and patterns of expression of these splice variants are highly conserved among vertebrates, suggestive of their biological importance; however the functions of EIIIA and EIIIB-containing FNs are unknown. To understand the role(s) of these splice variants, we deleted both EIIIA and EIIIB exons from the FN gene and observed embryonic lethality with incomplete penetrance by embryonic day 10.5. Deletion of both EIIIA and EIIIB exons did not affect synthesis or cell surface deposition of FN, indicating that embryonic lethality was due specifically to the absence of EIIIA and EIIIB exons from FN. EIIIA/EIIIB double-null embryos displayed multiple embryonic cardiovascular defects, including vascular hemorrhage, failure of remodeling embryonic and yolk sac vasculature, defective placental angiogenesis and heart defects. In addition, we observed defects in coverage and association with dorsal aortae of alpha-smooth-muscle-actin-positive cells. Our studies indicate that the presence or absence of EIIIA and EIIIB exons alters the function of FN and demonstrate the requirement for these alternatively spliced exons in cardiovascular development.",
author = "Sophie Astrof and Denise Crowley and Hynes, {Richard O.}",
year = "2007",
month = "11",
day = "1",
doi = "https://doi.org/10.1016/j.ydbio.2007.07.005",
language = "English (US)",
volume = "311",
pages = "11--24",
journal = "Developmental Biology",
issn = "0012-1606",
publisher = "Academic Press Inc.",
number = "1",

}

Multiple cardiovascular defects caused by the absence of alternatively spliced segments of fibronectin. / Astrof, Sophie; Crowley, Denise; Hynes, Richard O.

In: Developmental biology, Vol. 311, No. 1, 01.11.2007, p. 11-24.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Multiple cardiovascular defects caused by the absence of alternatively spliced segments of fibronectin

AU - Astrof, Sophie

AU - Crowley, Denise

AU - Hynes, Richard O.

PY - 2007/11/1

Y1 - 2007/11/1

N2 - Alternatively spliced variants of fibronectin (FN) containing exons EIIIA and EIIIB are expressed around newly forming vessels in development and disease but are downregulated in mature vasculature. The sequences and patterns of expression of these splice variants are highly conserved among vertebrates, suggestive of their biological importance; however the functions of EIIIA and EIIIB-containing FNs are unknown. To understand the role(s) of these splice variants, we deleted both EIIIA and EIIIB exons from the FN gene and observed embryonic lethality with incomplete penetrance by embryonic day 10.5. Deletion of both EIIIA and EIIIB exons did not affect synthesis or cell surface deposition of FN, indicating that embryonic lethality was due specifically to the absence of EIIIA and EIIIB exons from FN. EIIIA/EIIIB double-null embryos displayed multiple embryonic cardiovascular defects, including vascular hemorrhage, failure of remodeling embryonic and yolk sac vasculature, defective placental angiogenesis and heart defects. In addition, we observed defects in coverage and association with dorsal aortae of alpha-smooth-muscle-actin-positive cells. Our studies indicate that the presence or absence of EIIIA and EIIIB exons alters the function of FN and demonstrate the requirement for these alternatively spliced exons in cardiovascular development.

AB - Alternatively spliced variants of fibronectin (FN) containing exons EIIIA and EIIIB are expressed around newly forming vessels in development and disease but are downregulated in mature vasculature. The sequences and patterns of expression of these splice variants are highly conserved among vertebrates, suggestive of their biological importance; however the functions of EIIIA and EIIIB-containing FNs are unknown. To understand the role(s) of these splice variants, we deleted both EIIIA and EIIIB exons from the FN gene and observed embryonic lethality with incomplete penetrance by embryonic day 10.5. Deletion of both EIIIA and EIIIB exons did not affect synthesis or cell surface deposition of FN, indicating that embryonic lethality was due specifically to the absence of EIIIA and EIIIB exons from FN. EIIIA/EIIIB double-null embryos displayed multiple embryonic cardiovascular defects, including vascular hemorrhage, failure of remodeling embryonic and yolk sac vasculature, defective placental angiogenesis and heart defects. In addition, we observed defects in coverage and association with dorsal aortae of alpha-smooth-muscle-actin-positive cells. Our studies indicate that the presence or absence of EIIIA and EIIIB exons alters the function of FN and demonstrate the requirement for these alternatively spliced exons in cardiovascular development.

UR - http://www.scopus.com/inward/record.url?scp=35348890874&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=35348890874&partnerID=8YFLogxK

U2 - https://doi.org/10.1016/j.ydbio.2007.07.005

DO - https://doi.org/10.1016/j.ydbio.2007.07.005

M3 - Article

VL - 311

SP - 11

EP - 24

JO - Developmental Biology

JF - Developmental Biology

SN - 0012-1606

IS - 1

ER -