Roles for the winged helix transcription factors MF1 and MFH1 in cardiovascular development revealed by nonallelic noncomplementation of null alleles

Glenn E. Winnier, Tsutomu Kume, Keyu Deng, Rhonda Rogers, Justin Bundy, Cameron Raines, Michael A. Walter, Brigid L M Hogan, Simon Conway

Research output: Contribution to journalArticle

133 Citations (Scopus)

Abstract

The murine Mf1 and Mfh1 genes have overlapping patterns of expression in the embryo and encode forkhead/winged helix transcription factors with virtually identical DNA binding domains. Previous studies have shown that Mfh1 null mutants have severe cardiovascular defects, including interruptions and coarctations of the aortic arch and ventricular septal defects (Iida et al., Development 124, 4627-4638, 1997). Here, we show that Mf1(1acz) homozygous null mutants also have a similar spectrum of cardiovascular abnormalities. Moreover, most embryos doubly heterozygous for Mfh1(tm1) and Mf1(1acz) die before birth with interruptions and coarctations of the aortic arch, dysgenesis of the aortic and pulmonary valves, ventricular septal defects, and other cardiac anomalies. This nonallelic noncomplementation and the similar patterns of expression of the two genes in the mesenchyme and endothelial cells of the branchial arches, outflow tract, and heart suggest that Mf1 and Mfh1 play interactive roles in the morphogenesis of the cardiovascular system. Implications for the development of human congenital heart defects are discussed.

Original languageEnglish (US)
Pages (from-to)418-431
Number of pages14
JournalDevelopmental Biology
Volume213
Issue number2
DOIs
StatePublished - Sep 15 1999
Externally publishedYes

Fingerprint

Winged-Helix Transcription Factors
Ventricular Heart Septal Defects
Thoracic Aorta
Embryonic Structures
Alleles
Overlapping Genes
Cardiovascular Abnormalities
Branchial Region
Pulmonary Valve
Congenital Heart Defects
Human Development
Mesoderm
Cardiovascular System
Aortic Valve
Morphogenesis
Endothelial Cells
Parturition
Gene Expression
DNA

Keywords

  • Aortic arch
  • Cardiac failure
  • Forkhead
  • Heart development
  • Mouse embryo
  • Mutation
  • Winged helix

ASJC Scopus subject areas

  • Developmental Biology

Cite this

Roles for the winged helix transcription factors MF1 and MFH1 in cardiovascular development revealed by nonallelic noncomplementation of null alleles. / Winnier, Glenn E.; Kume, Tsutomu; Deng, Keyu; Rogers, Rhonda; Bundy, Justin; Raines, Cameron; Walter, Michael A.; Hogan, Brigid L M; Conway, Simon.

In: Developmental Biology, Vol. 213, No. 2, 15.09.1999, p. 418-431.

Research output: Contribution to journalArticle

Winnier, Glenn E. ; Kume, Tsutomu ; Deng, Keyu ; Rogers, Rhonda ; Bundy, Justin ; Raines, Cameron ; Walter, Michael A. ; Hogan, Brigid L M ; Conway, Simon. / Roles for the winged helix transcription factors MF1 and MFH1 in cardiovascular development revealed by nonallelic noncomplementation of null alleles. In: Developmental Biology. 1999 ; Vol. 213, No. 2. pp. 418-431.
@article{7ed5638f596c41d6af6b0c3a6d14bfde,
title = "Roles for the winged helix transcription factors MF1 and MFH1 in cardiovascular development revealed by nonallelic noncomplementation of null alleles",
abstract = "The murine Mf1 and Mfh1 genes have overlapping patterns of expression in the embryo and encode forkhead/winged helix transcription factors with virtually identical DNA binding domains. Previous studies have shown that Mfh1 null mutants have severe cardiovascular defects, including interruptions and coarctations of the aortic arch and ventricular septal defects (Iida et al., Development 124, 4627-4638, 1997). Here, we show that Mf1(1acz) homozygous null mutants also have a similar spectrum of cardiovascular abnormalities. Moreover, most embryos doubly heterozygous for Mfh1(tm1) and Mf1(1acz) die before birth with interruptions and coarctations of the aortic arch, dysgenesis of the aortic and pulmonary valves, ventricular septal defects, and other cardiac anomalies. This nonallelic noncomplementation and the similar patterns of expression of the two genes in the mesenchyme and endothelial cells of the branchial arches, outflow tract, and heart suggest that Mf1 and Mfh1 play interactive roles in the morphogenesis of the cardiovascular system. Implications for the development of human congenital heart defects are discussed.",
keywords = "Aortic arch, Cardiac failure, Forkhead, Heart development, Mouse embryo, Mutation, Winged helix",
author = "Winnier, {Glenn E.} and Tsutomu Kume and Keyu Deng and Rhonda Rogers and Justin Bundy and Cameron Raines and Walter, {Michael A.} and Hogan, {Brigid L M} and Simon Conway",
year = "1999",
month = "9",
day = "15",
doi = "10.1006/dbio.1999.9382",
language = "English (US)",
volume = "213",
pages = "418--431",
journal = "Developmental Biology",
issn = "0012-1606",
publisher = "Academic Press Inc.",
number = "2",

}

TY - JOUR

T1 - Roles for the winged helix transcription factors MF1 and MFH1 in cardiovascular development revealed by nonallelic noncomplementation of null alleles

AU - Winnier, Glenn E.

AU - Kume, Tsutomu

AU - Deng, Keyu

AU - Rogers, Rhonda

AU - Bundy, Justin

AU - Raines, Cameron

AU - Walter, Michael A.

AU - Hogan, Brigid L M

AU - Conway, Simon

PY - 1999/9/15

Y1 - 1999/9/15

N2 - The murine Mf1 and Mfh1 genes have overlapping patterns of expression in the embryo and encode forkhead/winged helix transcription factors with virtually identical DNA binding domains. Previous studies have shown that Mfh1 null mutants have severe cardiovascular defects, including interruptions and coarctations of the aortic arch and ventricular septal defects (Iida et al., Development 124, 4627-4638, 1997). Here, we show that Mf1(1acz) homozygous null mutants also have a similar spectrum of cardiovascular abnormalities. Moreover, most embryos doubly heterozygous for Mfh1(tm1) and Mf1(1acz) die before birth with interruptions and coarctations of the aortic arch, dysgenesis of the aortic and pulmonary valves, ventricular septal defects, and other cardiac anomalies. This nonallelic noncomplementation and the similar patterns of expression of the two genes in the mesenchyme and endothelial cells of the branchial arches, outflow tract, and heart suggest that Mf1 and Mfh1 play interactive roles in the morphogenesis of the cardiovascular system. Implications for the development of human congenital heart defects are discussed.

AB - The murine Mf1 and Mfh1 genes have overlapping patterns of expression in the embryo and encode forkhead/winged helix transcription factors with virtually identical DNA binding domains. Previous studies have shown that Mfh1 null mutants have severe cardiovascular defects, including interruptions and coarctations of the aortic arch and ventricular septal defects (Iida et al., Development 124, 4627-4638, 1997). Here, we show that Mf1(1acz) homozygous null mutants also have a similar spectrum of cardiovascular abnormalities. Moreover, most embryos doubly heterozygous for Mfh1(tm1) and Mf1(1acz) die before birth with interruptions and coarctations of the aortic arch, dysgenesis of the aortic and pulmonary valves, ventricular septal defects, and other cardiac anomalies. This nonallelic noncomplementation and the similar patterns of expression of the two genes in the mesenchyme and endothelial cells of the branchial arches, outflow tract, and heart suggest that Mf1 and Mfh1 play interactive roles in the morphogenesis of the cardiovascular system. Implications for the development of human congenital heart defects are discussed.

KW - Aortic arch

KW - Cardiac failure

KW - Forkhead

KW - Heart development

KW - Mouse embryo

KW - Mutation

KW - Winged helix

UR - http://www.scopus.com/inward/record.url?scp=0033568038&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033568038&partnerID=8YFLogxK

U2 - 10.1006/dbio.1999.9382

DO - 10.1006/dbio.1999.9382

M3 - Article

VL - 213

SP - 418

EP - 431

JO - Developmental Biology

JF - Developmental Biology

SN - 0012-1606

IS - 2

ER -