A highly conserved Wnt-dependent TCF4 binding site within the proximal enhancer of the anti-myogenic Msx1 gene supports expression within Pax3-expressing limb bud muscle precursor cells

Kerry A Miller, John Barrow, J. Martin Collinson, Scott Davidson, Marissa Lear, Robert E. Hill, Alasdair MacKenzie

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

The product of the Msxl gene is a potent inhibitor of muscle differentiation. Msxl is expressed in muscle precursor cells of the limb bud that also express Pax3. It is thought that Msxl may facilitate distal migration by delaying myogenesis in these cells. Despite the role played by Msxl in inhibiting muscle differentiation, nothing is known of the mechanisms that support the expression of the Msxl gene within limb bud muscle precursor cells. In the present study we have used a combination of comparative genomics, mouse transgenic analysis, in situ hybridisation and inimunohistochemistry to identify a highly conserved and tissue-specific regulatory sub-domain within the previously characterised Msxl gene proximal enhancer element that supports the expression of the Msxl gene in Pax3-expressing mouse limb pre-muscle masses. Furthermore, using a combination of in situ hybridisation, in vivo ChIP assay and transgenic explant culture analysis we provide evidence that Msxl expression in limb bud muscle precursor cells is dependent on the canonical Wnt/TCF signalling pathway that is important in muscle shape formation. The results of these studies provide evidence of a mechanistic link between the Wnt/TCF and the Msxl/Pax3/MyoD pathways within limb bud muscle precursor cells. (C) 2007 Elsevier Inc. All rights reserved.

Original languageEnglish
Pages (from-to)665-678
Number of pages14
JournalDevelopmental Biology
Volume311
Issue number2
DOIs
Publication statusPublished - 15 Nov 2007

Keywords

  • transcriptional regulation
  • comparative genomics
  • transgenic mouse
  • limb bud muscle precursor cells
  • Msx1
  • Pax3
  • Tcf4
  • Wnt signalling
  • homeobox gene
  • transcription factor
  • tooth development
  • beta-catenin
  • in-vivo
  • mouse
  • differentiation
  • promoter
  • mice
  • identification

Cite this

A highly conserved Wnt-dependent TCF4 binding site within the proximal enhancer of the anti-myogenic Msx1 gene supports expression within Pax3-expressing limb bud muscle precursor cells. / Miller, Kerry A; Barrow, John; Collinson, J. Martin; Davidson, Scott; Lear, Marissa; Hill, Robert E.; MacKenzie, Alasdair.

In: Developmental Biology, Vol. 311, No. 2, 15.11.2007, p. 665-678.

Research output: Contribution to journalArticle

@article{3324a9c5d1db43f4a6902199df96e3f4,
title = "A highly conserved Wnt-dependent TCF4 binding site within the proximal enhancer of the anti-myogenic Msx1 gene supports expression within Pax3-expressing limb bud muscle precursor cells",
abstract = "The product of the Msxl gene is a potent inhibitor of muscle differentiation. Msxl is expressed in muscle precursor cells of the limb bud that also express Pax3. It is thought that Msxl may facilitate distal migration by delaying myogenesis in these cells. Despite the role played by Msxl in inhibiting muscle differentiation, nothing is known of the mechanisms that support the expression of the Msxl gene within limb bud muscle precursor cells. In the present study we have used a combination of comparative genomics, mouse transgenic analysis, in situ hybridisation and inimunohistochemistry to identify a highly conserved and tissue-specific regulatory sub-domain within the previously characterised Msxl gene proximal enhancer element that supports the expression of the Msxl gene in Pax3-expressing mouse limb pre-muscle masses. Furthermore, using a combination of in situ hybridisation, in vivo ChIP assay and transgenic explant culture analysis we provide evidence that Msxl expression in limb bud muscle precursor cells is dependent on the canonical Wnt/TCF signalling pathway that is important in muscle shape formation. The results of these studies provide evidence of a mechanistic link between the Wnt/TCF and the Msxl/Pax3/MyoD pathways within limb bud muscle precursor cells. (C) 2007 Elsevier Inc. All rights reserved.",
keywords = "transcriptional regulation, comparative genomics, transgenic mouse, limb bud muscle precursor cells, Msx1, Pax3, Tcf4, Wnt signalling, homeobox gene, transcription factor, tooth development, beta-catenin, in-vivo, mouse, differentiation, promoter, mice, identification",
author = "Miller, {Kerry A} and John Barrow and Collinson, {J. Martin} and Scott Davidson and Marissa Lear and Hill, {Robert E.} and Alasdair MacKenzie",
year = "2007",
month = "11",
day = "15",
doi = "10.1016/j.ydbio.2007.07.022",
language = "English",
volume = "311",
pages = "665--678",
journal = "Developmental Biology",
issn = "0012-1606",
publisher = "Academic Press Inc.",
number = "2",

}

TY - JOUR

T1 - A highly conserved Wnt-dependent TCF4 binding site within the proximal enhancer of the anti-myogenic Msx1 gene supports expression within Pax3-expressing limb bud muscle precursor cells

AU - Miller, Kerry A

AU - Barrow, John

AU - Collinson, J. Martin

AU - Davidson, Scott

AU - Lear, Marissa

AU - Hill, Robert E.

AU - MacKenzie, Alasdair

PY - 2007/11/15

Y1 - 2007/11/15

N2 - The product of the Msxl gene is a potent inhibitor of muscle differentiation. Msxl is expressed in muscle precursor cells of the limb bud that also express Pax3. It is thought that Msxl may facilitate distal migration by delaying myogenesis in these cells. Despite the role played by Msxl in inhibiting muscle differentiation, nothing is known of the mechanisms that support the expression of the Msxl gene within limb bud muscle precursor cells. In the present study we have used a combination of comparative genomics, mouse transgenic analysis, in situ hybridisation and inimunohistochemistry to identify a highly conserved and tissue-specific regulatory sub-domain within the previously characterised Msxl gene proximal enhancer element that supports the expression of the Msxl gene in Pax3-expressing mouse limb pre-muscle masses. Furthermore, using a combination of in situ hybridisation, in vivo ChIP assay and transgenic explant culture analysis we provide evidence that Msxl expression in limb bud muscle precursor cells is dependent on the canonical Wnt/TCF signalling pathway that is important in muscle shape formation. The results of these studies provide evidence of a mechanistic link between the Wnt/TCF and the Msxl/Pax3/MyoD pathways within limb bud muscle precursor cells. (C) 2007 Elsevier Inc. All rights reserved.

AB - The product of the Msxl gene is a potent inhibitor of muscle differentiation. Msxl is expressed in muscle precursor cells of the limb bud that also express Pax3. It is thought that Msxl may facilitate distal migration by delaying myogenesis in these cells. Despite the role played by Msxl in inhibiting muscle differentiation, nothing is known of the mechanisms that support the expression of the Msxl gene within limb bud muscle precursor cells. In the present study we have used a combination of comparative genomics, mouse transgenic analysis, in situ hybridisation and inimunohistochemistry to identify a highly conserved and tissue-specific regulatory sub-domain within the previously characterised Msxl gene proximal enhancer element that supports the expression of the Msxl gene in Pax3-expressing mouse limb pre-muscle masses. Furthermore, using a combination of in situ hybridisation, in vivo ChIP assay and transgenic explant culture analysis we provide evidence that Msxl expression in limb bud muscle precursor cells is dependent on the canonical Wnt/TCF signalling pathway that is important in muscle shape formation. The results of these studies provide evidence of a mechanistic link between the Wnt/TCF and the Msxl/Pax3/MyoD pathways within limb bud muscle precursor cells. (C) 2007 Elsevier Inc. All rights reserved.

KW - transcriptional regulation

KW - comparative genomics

KW - transgenic mouse

KW - limb bud muscle precursor cells

KW - Msx1

KW - Pax3

KW - Tcf4

KW - Wnt signalling

KW - homeobox gene

KW - transcription factor

KW - tooth development

KW - beta-catenin

KW - in-vivo

KW - mouse

KW - differentiation

KW - promoter

KW - mice

KW - identification

U2 - 10.1016/j.ydbio.2007.07.022

DO - 10.1016/j.ydbio.2007.07.022

M3 - Article

VL - 311

SP - 665

EP - 678

JO - Developmental Biology

JF - Developmental Biology

SN - 0012-1606

IS - 2

ER -