DNA binding-dependent and -independent functions of the Hand2 transcription factor during mouse embryogenesis

Ning Liu, Ana C. Barbosa, Shelby L. Chapman, Svetlana Bezprozvannaya, Xiaoxia Qi, James A. Richardson, Hiromi Yanagisawa, Eric N. Olson

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

The basic helix-loop-helix (bHLH) transcription factor Hand2 is required for growth and development of the heart, branchial arches and limb buds. To determine whether DNA binding is required for Hand2 to regulate the growth and development of these different embryonic tissues, we generated mutant mice in which the Hand2 locus was modified by a mutation (referred to as Hand2EDE) that abolished the DNA-binding activity of Hand2, leaving the remainder of the protein intact. In contrast to Hand2 null embryos, which display right ventricular hypoplasia and vascular abnormalities, causing severe growth retardation by E9.5 and death by E10.5, early development of the heart appeared remarkably normal in homozygous Hand2EDE mutant embryos. These mutant embryos also lacked the early defects in growth of the branchial arches seen in Hand2 null embryos and survived up to 2 to 3 days longer than did Hand2 null embryos. However, Hand2EDE mutant embryos exhibited growth defects in the limb buds similar to those of Hand2 null embryos. These findings suggest that Hand2 regulates tissue growth and development in vivo through DNA binding-dependent and -independent mechanisms.

Original languageEnglish (US)
Pages (from-to)933-942
Number of pages10
JournalDevelopment
Volume136
Issue number6
DOIs
StatePublished - Mar 15 2009

Fingerprint

Embryonic Development
Transcription Factors
Embryonic Structures
DNA
Growth and Development
Branchial Region
Limb Buds
Growth
Basic Helix-Loop-Helix Transcription Factors
Blood Vessels
Mutation
Proteins

Keywords

  • bHLH
  • Craniofacial development
  • Hand2
  • Heart development
  • Limb development

ASJC Scopus subject areas

  • Developmental Biology
  • Molecular Biology

Cite this

DNA binding-dependent and -independent functions of the Hand2 transcription factor during mouse embryogenesis. / Liu, Ning; Barbosa, Ana C.; Chapman, Shelby L.; Bezprozvannaya, Svetlana; Qi, Xiaoxia; Richardson, James A.; Yanagisawa, Hiromi; Olson, Eric N.

In: Development, Vol. 136, No. 6, 15.03.2009, p. 933-942.

Research output: Contribution to journalArticle

Liu, Ning ; Barbosa, Ana C. ; Chapman, Shelby L. ; Bezprozvannaya, Svetlana ; Qi, Xiaoxia ; Richardson, James A. ; Yanagisawa, Hiromi ; Olson, Eric N. / DNA binding-dependent and -independent functions of the Hand2 transcription factor during mouse embryogenesis. In: Development. 2009 ; Vol. 136, No. 6. pp. 933-942.
@article{546c407271af434683919100dcabdc74,
title = "DNA binding-dependent and -independent functions of the Hand2 transcription factor during mouse embryogenesis",
abstract = "The basic helix-loop-helix (bHLH) transcription factor Hand2 is required for growth and development of the heart, branchial arches and limb buds. To determine whether DNA binding is required for Hand2 to regulate the growth and development of these different embryonic tissues, we generated mutant mice in which the Hand2 locus was modified by a mutation (referred to as Hand2EDE) that abolished the DNA-binding activity of Hand2, leaving the remainder of the protein intact. In contrast to Hand2 null embryos, which display right ventricular hypoplasia and vascular abnormalities, causing severe growth retardation by E9.5 and death by E10.5, early development of the heart appeared remarkably normal in homozygous Hand2EDE mutant embryos. These mutant embryos also lacked the early defects in growth of the branchial arches seen in Hand2 null embryos and survived up to 2 to 3 days longer than did Hand2 null embryos. However, Hand2EDE mutant embryos exhibited growth defects in the limb buds similar to those of Hand2 null embryos. These findings suggest that Hand2 regulates tissue growth and development in vivo through DNA binding-dependent and -independent mechanisms.",
keywords = "bHLH, Craniofacial development, Hand2, Heart development, Limb development",
author = "Ning Liu and Barbosa, {Ana C.} and Chapman, {Shelby L.} and Svetlana Bezprozvannaya and Xiaoxia Qi and Richardson, {James A.} and Hiromi Yanagisawa and Olson, {Eric N.}",
year = "2009",
month = "3",
day = "15",
doi = "10.1242/dev.034025",
language = "English (US)",
volume = "136",
pages = "933--942",
journal = "Development (Cambridge)",
issn = "0950-1991",
publisher = "Company of Biologists Ltd",
number = "6",

}

TY - JOUR

T1 - DNA binding-dependent and -independent functions of the Hand2 transcription factor during mouse embryogenesis

AU - Liu, Ning

AU - Barbosa, Ana C.

AU - Chapman, Shelby L.

AU - Bezprozvannaya, Svetlana

AU - Qi, Xiaoxia

AU - Richardson, James A.

AU - Yanagisawa, Hiromi

AU - Olson, Eric N.

PY - 2009/3/15

Y1 - 2009/3/15

N2 - The basic helix-loop-helix (bHLH) transcription factor Hand2 is required for growth and development of the heart, branchial arches and limb buds. To determine whether DNA binding is required for Hand2 to regulate the growth and development of these different embryonic tissues, we generated mutant mice in which the Hand2 locus was modified by a mutation (referred to as Hand2EDE) that abolished the DNA-binding activity of Hand2, leaving the remainder of the protein intact. In contrast to Hand2 null embryos, which display right ventricular hypoplasia and vascular abnormalities, causing severe growth retardation by E9.5 and death by E10.5, early development of the heart appeared remarkably normal in homozygous Hand2EDE mutant embryos. These mutant embryos also lacked the early defects in growth of the branchial arches seen in Hand2 null embryos and survived up to 2 to 3 days longer than did Hand2 null embryos. However, Hand2EDE mutant embryos exhibited growth defects in the limb buds similar to those of Hand2 null embryos. These findings suggest that Hand2 regulates tissue growth and development in vivo through DNA binding-dependent and -independent mechanisms.

AB - The basic helix-loop-helix (bHLH) transcription factor Hand2 is required for growth and development of the heart, branchial arches and limb buds. To determine whether DNA binding is required for Hand2 to regulate the growth and development of these different embryonic tissues, we generated mutant mice in which the Hand2 locus was modified by a mutation (referred to as Hand2EDE) that abolished the DNA-binding activity of Hand2, leaving the remainder of the protein intact. In contrast to Hand2 null embryos, which display right ventricular hypoplasia and vascular abnormalities, causing severe growth retardation by E9.5 and death by E10.5, early development of the heart appeared remarkably normal in homozygous Hand2EDE mutant embryos. These mutant embryos also lacked the early defects in growth of the branchial arches seen in Hand2 null embryos and survived up to 2 to 3 days longer than did Hand2 null embryos. However, Hand2EDE mutant embryos exhibited growth defects in the limb buds similar to those of Hand2 null embryos. These findings suggest that Hand2 regulates tissue growth and development in vivo through DNA binding-dependent and -independent mechanisms.

KW - bHLH

KW - Craniofacial development

KW - Hand2

KW - Heart development

KW - Limb development

UR - http://www.scopus.com/inward/record.url?scp=66149089187&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=66149089187&partnerID=8YFLogxK

U2 - 10.1242/dev.034025

DO - 10.1242/dev.034025

M3 - Article

C2 - 19211672

AN - SCOPUS:66149089187

VL - 136

SP - 933

EP - 942

JO - Development (Cambridge)

JF - Development (Cambridge)

SN - 0950-1991

IS - 6

ER -