Ectodermal FGFs induce perinodular inhibition of limb chondrogenesis in vitro and in vivo via FGF receptor 2

Marie Z. Moftah, Sherry A. Downie, Natalie B. Bronstein, Nadezhda Mezentseva, Jiayu Pu, Pamela A. Maher, Stuart A. Newman

Research output: Contribution to journalArticle

60 Citations (Scopus)

Abstract

The formation of cartilage elements in the developing vertebrate limb, where they serve as primordia for the appendicular skeleton, is preceded by the appearance of discrete cellular condensations. Control of the size and spacing of these condensations is a key aspect of skeletal pattern formation. Limb bud cell cultures grown in the absence of ectoderm formed continuous sheet-like masses of cartilage. With the inclusion of ectoderm, these cultures produced one or more cartilage nodules surrounded by zones of noncartilaginous mesenchyme. Ectodermal fibroblast growth factors (FGF2 and FGF8), but not a mesodermal FGF (FGF7), substituted for ectoderm in inhibiting chondrogenic gene expression, with some combinations of the two ectodermal factors leading to well-spaced cartilage nodules of relatively uniform size. Treatment of cultures with SU5402, an inhibitor FGF receptor tyrosine kinase activity, rendered FGFs ineffective in inducing perinodular inhibition. Inhibition of production of FGF receptor 2 (FGFR2) by transfection of wing and leg cell cultures with antisense oligodeoxynucleotides blocked appearance of ectoderm- or FGF-induced zones of perinodular inhibition of chondrogenesis and, when introduced into the limb buds of developing embryos, led to shorter, thicker, and fused cartilage elements. Because FGFR2 is expressed mainly at sites of precartilage condensation during limb development in vivo and in vitro, these results suggest that activation of FGFR2 by FGFs during development elicits a lateral inhibitor of chondrogenesis that limits the expansion of developing skeletal elements.

Original languageEnglish (US)
Pages (from-to)270-282
Number of pages13
JournalDevelopmental Biology
Volume249
Issue number2
DOIs
StatePublished - 2002
Externally publishedYes

Fingerprint

Chondrogenesis
Fibroblast Growth Factor Receptors
Fibroblast Growth Factor 2
Ectoderm
Cartilage
Extremities
Limb Buds
Cell Culture Techniques
Fibroblast Growth Factors
Oligodeoxyribonucleotides
Mesoderm
Skeleton
Protein-Tyrosine Kinases
Transfection
Vertebrates
Leg
Embryonic Structures
In Vitro Techniques
Gene Expression

Keywords

  • FGF receptor
  • Fibroblast growth factor
  • Lateral inhibition
  • Limb development
  • Pattern formation

ASJC Scopus subject areas

  • Developmental Biology

Cite this

Ectodermal FGFs induce perinodular inhibition of limb chondrogenesis in vitro and in vivo via FGF receptor 2. / Moftah, Marie Z.; Downie, Sherry A.; Bronstein, Natalie B.; Mezentseva, Nadezhda; Pu, Jiayu; Maher, Pamela A.; Newman, Stuart A.

In: Developmental Biology, Vol. 249, No. 2, 2002, p. 270-282.

Research output: Contribution to journalArticle

Moftah, Marie Z. ; Downie, Sherry A. ; Bronstein, Natalie B. ; Mezentseva, Nadezhda ; Pu, Jiayu ; Maher, Pamela A. ; Newman, Stuart A. / Ectodermal FGFs induce perinodular inhibition of limb chondrogenesis in vitro and in vivo via FGF receptor 2. In: Developmental Biology. 2002 ; Vol. 249, No. 2. pp. 270-282.
@article{2bf5d25f04744895976531ddb47626a6,
title = "Ectodermal FGFs induce perinodular inhibition of limb chondrogenesis in vitro and in vivo via FGF receptor 2",
abstract = "The formation of cartilage elements in the developing vertebrate limb, where they serve as primordia for the appendicular skeleton, is preceded by the appearance of discrete cellular condensations. Control of the size and spacing of these condensations is a key aspect of skeletal pattern formation. Limb bud cell cultures grown in the absence of ectoderm formed continuous sheet-like masses of cartilage. With the inclusion of ectoderm, these cultures produced one or more cartilage nodules surrounded by zones of noncartilaginous mesenchyme. Ectodermal fibroblast growth factors (FGF2 and FGF8), but not a mesodermal FGF (FGF7), substituted for ectoderm in inhibiting chondrogenic gene expression, with some combinations of the two ectodermal factors leading to well-spaced cartilage nodules of relatively uniform size. Treatment of cultures with SU5402, an inhibitor FGF receptor tyrosine kinase activity, rendered FGFs ineffective in inducing perinodular inhibition. Inhibition of production of FGF receptor 2 (FGFR2) by transfection of wing and leg cell cultures with antisense oligodeoxynucleotides blocked appearance of ectoderm- or FGF-induced zones of perinodular inhibition of chondrogenesis and, when introduced into the limb buds of developing embryos, led to shorter, thicker, and fused cartilage elements. Because FGFR2 is expressed mainly at sites of precartilage condensation during limb development in vivo and in vitro, these results suggest that activation of FGFR2 by FGFs during development elicits a lateral inhibitor of chondrogenesis that limits the expansion of developing skeletal elements.",
keywords = "FGF receptor, Fibroblast growth factor, Lateral inhibition, Limb development, Pattern formation",
author = "Moftah, {Marie Z.} and Downie, {Sherry A.} and Bronstein, {Natalie B.} and Nadezhda Mezentseva and Jiayu Pu and Maher, {Pamela A.} and Newman, {Stuart A.}",
year = "2002",
doi = "10.1006/dbio.2002.0766",
language = "English (US)",
volume = "249",
pages = "270--282",
journal = "Developmental Biology",
issn = "0012-1606",
publisher = "Academic Press Inc.",
number = "2",

}

TY - JOUR

T1 - Ectodermal FGFs induce perinodular inhibition of limb chondrogenesis in vitro and in vivo via FGF receptor 2

AU - Moftah, Marie Z.

AU - Downie, Sherry A.

AU - Bronstein, Natalie B.

AU - Mezentseva, Nadezhda

AU - Pu, Jiayu

AU - Maher, Pamela A.

AU - Newman, Stuart A.

PY - 2002

Y1 - 2002

N2 - The formation of cartilage elements in the developing vertebrate limb, where they serve as primordia for the appendicular skeleton, is preceded by the appearance of discrete cellular condensations. Control of the size and spacing of these condensations is a key aspect of skeletal pattern formation. Limb bud cell cultures grown in the absence of ectoderm formed continuous sheet-like masses of cartilage. With the inclusion of ectoderm, these cultures produced one or more cartilage nodules surrounded by zones of noncartilaginous mesenchyme. Ectodermal fibroblast growth factors (FGF2 and FGF8), but not a mesodermal FGF (FGF7), substituted for ectoderm in inhibiting chondrogenic gene expression, with some combinations of the two ectodermal factors leading to well-spaced cartilage nodules of relatively uniform size. Treatment of cultures with SU5402, an inhibitor FGF receptor tyrosine kinase activity, rendered FGFs ineffective in inducing perinodular inhibition. Inhibition of production of FGF receptor 2 (FGFR2) by transfection of wing and leg cell cultures with antisense oligodeoxynucleotides blocked appearance of ectoderm- or FGF-induced zones of perinodular inhibition of chondrogenesis and, when introduced into the limb buds of developing embryos, led to shorter, thicker, and fused cartilage elements. Because FGFR2 is expressed mainly at sites of precartilage condensation during limb development in vivo and in vitro, these results suggest that activation of FGFR2 by FGFs during development elicits a lateral inhibitor of chondrogenesis that limits the expansion of developing skeletal elements.

AB - The formation of cartilage elements in the developing vertebrate limb, where they serve as primordia for the appendicular skeleton, is preceded by the appearance of discrete cellular condensations. Control of the size and spacing of these condensations is a key aspect of skeletal pattern formation. Limb bud cell cultures grown in the absence of ectoderm formed continuous sheet-like masses of cartilage. With the inclusion of ectoderm, these cultures produced one or more cartilage nodules surrounded by zones of noncartilaginous mesenchyme. Ectodermal fibroblast growth factors (FGF2 and FGF8), but not a mesodermal FGF (FGF7), substituted for ectoderm in inhibiting chondrogenic gene expression, with some combinations of the two ectodermal factors leading to well-spaced cartilage nodules of relatively uniform size. Treatment of cultures with SU5402, an inhibitor FGF receptor tyrosine kinase activity, rendered FGFs ineffective in inducing perinodular inhibition. Inhibition of production of FGF receptor 2 (FGFR2) by transfection of wing and leg cell cultures with antisense oligodeoxynucleotides blocked appearance of ectoderm- or FGF-induced zones of perinodular inhibition of chondrogenesis and, when introduced into the limb buds of developing embryos, led to shorter, thicker, and fused cartilage elements. Because FGFR2 is expressed mainly at sites of precartilage condensation during limb development in vivo and in vitro, these results suggest that activation of FGFR2 by FGFs during development elicits a lateral inhibitor of chondrogenesis that limits the expansion of developing skeletal elements.

KW - FGF receptor

KW - Fibroblast growth factor

KW - Lateral inhibition

KW - Limb development

KW - Pattern formation

UR - http://www.scopus.com/inward/record.url?scp=0036384136&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036384136&partnerID=8YFLogxK

U2 - 10.1006/dbio.2002.0766

DO - 10.1006/dbio.2002.0766

M3 - Article

VL - 249

SP - 270

EP - 282

JO - Developmental Biology

JF - Developmental Biology

SN - 0012-1606

IS - 2

ER -