dHAND-Cre transgenic mice reveal specific potential functions of dHAND during craniofacial development

Louis Bruno Ruest, Marcus Dager, Hiromi Yanagisawa, Jeroen Charité, Robert E Hammer, Eric N Olson, Masashi Yanagisawa, David E. Clouthier

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Most of the bone, cartilage, and connective tissue of the craniofacial region arise from cephalic neural crest cells. Presumably, patterning differences in crest cells are a result of regional action of transcription factors within the developing pharyngeal arches. The basic helix-loop-helix transcription factor dHAND/HAND2 is expressed throughout much of the neural crest-derived mesenchyme of the pharyngeal arches, suggesting that it plays a crucial role in craniofacial development. However, targeted inactivation of the dHAND gene results in embryonic lethality by E10.5 due to vascular defects, preventing further analysis of the role of dHAND in cephalic neural crest cell development. In order to examine putative roles of dHAND during later stages of embryogenesis, we have used a transgenic lineage marker approach, in which a portion of the dHAND upstream region containing an enhancer that directs dHAND expression to the pharyngeal arches is used to drive Cre recombinase expression. By crossing these dHAND-Cre transgenic mice with R26R mice, we can follow the fate of cells that expressed dHAND at any time during development by examining β-galactosidase activity. We show that dHAND is first expressed in postmigratory cephalic neural crest cells within the pharyngeal arches. In older embryos, β-galactosidase-labeled cells are observed in most of the neural crest-derived lower jaw skeleton and surrounding connective tissues. However, labeled cells only contribute to substructures within the middle ear, indicating that our transgene is not globally expressed in cephalic neural crest cells within the pharyngeal arches. Moreover, dHAND-Cre mice will provide a valuable tool for tissue-specific inactivation of gene expression in multiple tissue types of neural crest origin.

Original languageEnglish (US)
Pages (from-to)263-277
Number of pages15
JournalDevelopmental Biology
Volume257
Issue number2
DOIs
StatePublished - May 15 2003

Fingerprint

Neural Crest
Branchial Region
Transgenic Mice
Head
Galactosidases
Connective Tissue
Basic Helix-Loop-Helix Transcription Factors
Gene Silencing
Mesoderm
Middle Ear
Jaw
Transgenes
Skeleton
Cartilage
Embryonic Development
Blood Vessels
Transcription Factors
Embryonic Structures
Gene Expression
Bone and Bones

Keywords

  • Cephalic neural crest
  • Cre recombinase
  • dHAND/HAND2
  • Facial development
  • Neural crest enhancer
  • Transgenic mouse

ASJC Scopus subject areas

  • Developmental Biology

Cite this

dHAND-Cre transgenic mice reveal specific potential functions of dHAND during craniofacial development. / Ruest, Louis Bruno; Dager, Marcus; Yanagisawa, Hiromi; Charité, Jeroen; Hammer, Robert E; Olson, Eric N; Yanagisawa, Masashi; Clouthier, David E.

In: Developmental Biology, Vol. 257, No. 2, 15.05.2003, p. 263-277.

Research output: Contribution to journalArticle

Ruest, Louis Bruno ; Dager, Marcus ; Yanagisawa, Hiromi ; Charité, Jeroen ; Hammer, Robert E ; Olson, Eric N ; Yanagisawa, Masashi ; Clouthier, David E. / dHAND-Cre transgenic mice reveal specific potential functions of dHAND during craniofacial development. In: Developmental Biology. 2003 ; Vol. 257, No. 2. pp. 263-277.
@article{80005f0bb66b42d5aa236dea63ae4132,
title = "dHAND-Cre transgenic mice reveal specific potential functions of dHAND during craniofacial development",
abstract = "Most of the bone, cartilage, and connective tissue of the craniofacial region arise from cephalic neural crest cells. Presumably, patterning differences in crest cells are a result of regional action of transcription factors within the developing pharyngeal arches. The basic helix-loop-helix transcription factor dHAND/HAND2 is expressed throughout much of the neural crest-derived mesenchyme of the pharyngeal arches, suggesting that it plays a crucial role in craniofacial development. However, targeted inactivation of the dHAND gene results in embryonic lethality by E10.5 due to vascular defects, preventing further analysis of the role of dHAND in cephalic neural crest cell development. In order to examine putative roles of dHAND during later stages of embryogenesis, we have used a transgenic lineage marker approach, in which a portion of the dHAND upstream region containing an enhancer that directs dHAND expression to the pharyngeal arches is used to drive Cre recombinase expression. By crossing these dHAND-Cre transgenic mice with R26R mice, we can follow the fate of cells that expressed dHAND at any time during development by examining β-galactosidase activity. We show that dHAND is first expressed in postmigratory cephalic neural crest cells within the pharyngeal arches. In older embryos, β-galactosidase-labeled cells are observed in most of the neural crest-derived lower jaw skeleton and surrounding connective tissues. However, labeled cells only contribute to substructures within the middle ear, indicating that our transgene is not globally expressed in cephalic neural crest cells within the pharyngeal arches. Moreover, dHAND-Cre mice will provide a valuable tool for tissue-specific inactivation of gene expression in multiple tissue types of neural crest origin.",
keywords = "Cephalic neural crest, Cre recombinase, dHAND/HAND2, Facial development, Neural crest enhancer, Transgenic mouse",
author = "Ruest, {Louis Bruno} and Marcus Dager and Hiromi Yanagisawa and Jeroen Charit{\'e} and Hammer, {Robert E} and Olson, {Eric N} and Masashi Yanagisawa and Clouthier, {David E.}",
year = "2003",
month = "5",
day = "15",
doi = "10.1016/S0012-1606(03)00068-X",
language = "English (US)",
volume = "257",
pages = "263--277",
journal = "Developmental Biology",
issn = "0012-1606",
publisher = "Academic Press Inc.",
number = "2",

}

TY - JOUR

T1 - dHAND-Cre transgenic mice reveal specific potential functions of dHAND during craniofacial development

AU - Ruest, Louis Bruno

AU - Dager, Marcus

AU - Yanagisawa, Hiromi

AU - Charité, Jeroen

AU - Hammer, Robert E

AU - Olson, Eric N

AU - Yanagisawa, Masashi

AU - Clouthier, David E.

PY - 2003/5/15

Y1 - 2003/5/15

N2 - Most of the bone, cartilage, and connective tissue of the craniofacial region arise from cephalic neural crest cells. Presumably, patterning differences in crest cells are a result of regional action of transcription factors within the developing pharyngeal arches. The basic helix-loop-helix transcription factor dHAND/HAND2 is expressed throughout much of the neural crest-derived mesenchyme of the pharyngeal arches, suggesting that it plays a crucial role in craniofacial development. However, targeted inactivation of the dHAND gene results in embryonic lethality by E10.5 due to vascular defects, preventing further analysis of the role of dHAND in cephalic neural crest cell development. In order to examine putative roles of dHAND during later stages of embryogenesis, we have used a transgenic lineage marker approach, in which a portion of the dHAND upstream region containing an enhancer that directs dHAND expression to the pharyngeal arches is used to drive Cre recombinase expression. By crossing these dHAND-Cre transgenic mice with R26R mice, we can follow the fate of cells that expressed dHAND at any time during development by examining β-galactosidase activity. We show that dHAND is first expressed in postmigratory cephalic neural crest cells within the pharyngeal arches. In older embryos, β-galactosidase-labeled cells are observed in most of the neural crest-derived lower jaw skeleton and surrounding connective tissues. However, labeled cells only contribute to substructures within the middle ear, indicating that our transgene is not globally expressed in cephalic neural crest cells within the pharyngeal arches. Moreover, dHAND-Cre mice will provide a valuable tool for tissue-specific inactivation of gene expression in multiple tissue types of neural crest origin.

AB - Most of the bone, cartilage, and connective tissue of the craniofacial region arise from cephalic neural crest cells. Presumably, patterning differences in crest cells are a result of regional action of transcription factors within the developing pharyngeal arches. The basic helix-loop-helix transcription factor dHAND/HAND2 is expressed throughout much of the neural crest-derived mesenchyme of the pharyngeal arches, suggesting that it plays a crucial role in craniofacial development. However, targeted inactivation of the dHAND gene results in embryonic lethality by E10.5 due to vascular defects, preventing further analysis of the role of dHAND in cephalic neural crest cell development. In order to examine putative roles of dHAND during later stages of embryogenesis, we have used a transgenic lineage marker approach, in which a portion of the dHAND upstream region containing an enhancer that directs dHAND expression to the pharyngeal arches is used to drive Cre recombinase expression. By crossing these dHAND-Cre transgenic mice with R26R mice, we can follow the fate of cells that expressed dHAND at any time during development by examining β-galactosidase activity. We show that dHAND is first expressed in postmigratory cephalic neural crest cells within the pharyngeal arches. In older embryos, β-galactosidase-labeled cells are observed in most of the neural crest-derived lower jaw skeleton and surrounding connective tissues. However, labeled cells only contribute to substructures within the middle ear, indicating that our transgene is not globally expressed in cephalic neural crest cells within the pharyngeal arches. Moreover, dHAND-Cre mice will provide a valuable tool for tissue-specific inactivation of gene expression in multiple tissue types of neural crest origin.

KW - Cephalic neural crest

KW - Cre recombinase

KW - dHAND/HAND2

KW - Facial development

KW - Neural crest enhancer

KW - Transgenic mouse

UR - http://www.scopus.com/inward/record.url?scp=0037447991&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037447991&partnerID=8YFLogxK

U2 - 10.1016/S0012-1606(03)00068-X

DO - 10.1016/S0012-1606(03)00068-X

M3 - Article

C2 - 12729557

AN - SCOPUS:0037447991

VL - 257

SP - 263

EP - 277

JO - Developmental Biology

JF - Developmental Biology

SN - 0012-1606

IS - 2

ER -