Sonic hedgehog functions as a mitogen during bell stage of odontogenesis

Changshan Wu, Tsuyoshi Shimo, Mufei Liu, Maurizio Pacifici, Eiki Koyama

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Epithelial-mesenchymal interactions are required for tissue growth and gene expression patterns during odontogenesis. We showed previously that Sonic hedgehog (SHH) is detectable in both dental epithelium and mesenchyme, while Shh transcripts are present in dental epithelium only, suggesting that SHH functions as an autocrine signal in epithelium and a paracrine signal in mesenchyme. This hypothesis was tested here. We found by in situ hybridization that the SHH autocrine receptor Ptch-2 is indeed expressed in dental epithelium whereas the paracrine receptor Ptc is expressed in mesenchyme. Bovine bell stage tooth germs were microsurgically separated into epithelial and mesenchymal portions and the resulting tissue fragments were organ-cultured. In epithelium fragments cultured by themselves, gene expression of Shh and Gli-1 (a putative transcriptional mediator of hedgehog signaling) was significantly decreased in both inner dental epithelium and stratum intermedium layers; this was accompanied by a sharp drop in epithelial cell proliferation. However, in companion control tissue fragments containing both epithelium and mesenchyme, Shh and Gli-1 expression as well as cell proliferation were maintained. Treatment of dental epithelial or mesenchymal cell populations in monolayer cultures with exogenous recombinant SHH stimulated cell proliferation. Together, the data provide clear evidence that Shh is synthesized by dental epithelium, reaches the underlying mesenchyme, and appears to act as an autocrine mitogen for epithelial cells and a paracrine mitogen for mesenchymal cells, thus exerting crucial functions in tooth germ growth, morphogenesis, and tissue-tissue interactions of bell stage of odontogenesis.

Original languageEnglish
Pages (from-to)92-96
Number of pages5
JournalConnective Tissue Research
Volume44
Issue numberSUPPL. 1
Publication statusPublished - 2003

Fingerprint

Odontogenesis
Mitogens
Epithelium
Tissue
Mesoderm
Cell proliferation
Tooth
Gene expression
Tooth Germ
Cell Proliferation
Cell culture
Epithelial Cells
Monolayers
Gene Expression
Cells
Growth
Morphogenesis
In Situ Hybridization

Keywords

  • Cell proliferation
  • Gli-1
  • Inner dental epithelium
  • Odontogenesis
  • Patched
  • Sonic hedgehog
  • Stratum intermedium

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Nephrology
  • Cell Biology
  • Orthopedics and Sports Medicine

Cite this

Wu, C., Shimo, T., Liu, M., Pacifici, M., & Koyama, E. (2003). Sonic hedgehog functions as a mitogen during bell stage of odontogenesis. Connective Tissue Research, 44(SUPPL. 1), 92-96.

Sonic hedgehog functions as a mitogen during bell stage of odontogenesis. / Wu, Changshan; Shimo, Tsuyoshi; Liu, Mufei; Pacifici, Maurizio; Koyama, Eiki.

In: Connective Tissue Research, Vol. 44, No. SUPPL. 1, 2003, p. 92-96.

Research output: Contribution to journalArticle

Wu, C, Shimo, T, Liu, M, Pacifici, M & Koyama, E 2003, 'Sonic hedgehog functions as a mitogen during bell stage of odontogenesis', Connective Tissue Research, vol. 44, no. SUPPL. 1, pp. 92-96.
Wu C, Shimo T, Liu M, Pacifici M, Koyama E. Sonic hedgehog functions as a mitogen during bell stage of odontogenesis. Connective Tissue Research. 2003;44(SUPPL. 1):92-96.
Wu, Changshan ; Shimo, Tsuyoshi ; Liu, Mufei ; Pacifici, Maurizio ; Koyama, Eiki. / Sonic hedgehog functions as a mitogen during bell stage of odontogenesis. In: Connective Tissue Research. 2003 ; Vol. 44, No. SUPPL. 1. pp. 92-96.
@article{ef1acabab9d64e878c01a761a98c87a2,
title = "Sonic hedgehog functions as a mitogen during bell stage of odontogenesis",
abstract = "Epithelial-mesenchymal interactions are required for tissue growth and gene expression patterns during odontogenesis. We showed previously that Sonic hedgehog (SHH) is detectable in both dental epithelium and mesenchyme, while Shh transcripts are present in dental epithelium only, suggesting that SHH functions as an autocrine signal in epithelium and a paracrine signal in mesenchyme. This hypothesis was tested here. We found by in situ hybridization that the SHH autocrine receptor Ptch-2 is indeed expressed in dental epithelium whereas the paracrine receptor Ptc is expressed in mesenchyme. Bovine bell stage tooth germs were microsurgically separated into epithelial and mesenchymal portions and the resulting tissue fragments were organ-cultured. In epithelium fragments cultured by themselves, gene expression of Shh and Gli-1 (a putative transcriptional mediator of hedgehog signaling) was significantly decreased in both inner dental epithelium and stratum intermedium layers; this was accompanied by a sharp drop in epithelial cell proliferation. However, in companion control tissue fragments containing both epithelium and mesenchyme, Shh and Gli-1 expression as well as cell proliferation were maintained. Treatment of dental epithelial or mesenchymal cell populations in monolayer cultures with exogenous recombinant SHH stimulated cell proliferation. Together, the data provide clear evidence that Shh is synthesized by dental epithelium, reaches the underlying mesenchyme, and appears to act as an autocrine mitogen for epithelial cells and a paracrine mitogen for mesenchymal cells, thus exerting crucial functions in tooth germ growth, morphogenesis, and tissue-tissue interactions of bell stage of odontogenesis.",
keywords = "Cell proliferation, Gli-1, Inner dental epithelium, Odontogenesis, Patched, Sonic hedgehog, Stratum intermedium",
author = "Changshan Wu and Tsuyoshi Shimo and Mufei Liu and Maurizio Pacifici and Eiki Koyama",
year = "2003",
language = "English",
volume = "44",
pages = "92--96",
journal = "Connective Tissue Research",
issn = "0300-8207",
publisher = "Informa Healthcare",
number = "SUPPL. 1",

}

TY - JOUR

T1 - Sonic hedgehog functions as a mitogen during bell stage of odontogenesis

AU - Wu, Changshan

AU - Shimo, Tsuyoshi

AU - Liu, Mufei

AU - Pacifici, Maurizio

AU - Koyama, Eiki

PY - 2003

Y1 - 2003

N2 - Epithelial-mesenchymal interactions are required for tissue growth and gene expression patterns during odontogenesis. We showed previously that Sonic hedgehog (SHH) is detectable in both dental epithelium and mesenchyme, while Shh transcripts are present in dental epithelium only, suggesting that SHH functions as an autocrine signal in epithelium and a paracrine signal in mesenchyme. This hypothesis was tested here. We found by in situ hybridization that the SHH autocrine receptor Ptch-2 is indeed expressed in dental epithelium whereas the paracrine receptor Ptc is expressed in mesenchyme. Bovine bell stage tooth germs were microsurgically separated into epithelial and mesenchymal portions and the resulting tissue fragments were organ-cultured. In epithelium fragments cultured by themselves, gene expression of Shh and Gli-1 (a putative transcriptional mediator of hedgehog signaling) was significantly decreased in both inner dental epithelium and stratum intermedium layers; this was accompanied by a sharp drop in epithelial cell proliferation. However, in companion control tissue fragments containing both epithelium and mesenchyme, Shh and Gli-1 expression as well as cell proliferation were maintained. Treatment of dental epithelial or mesenchymal cell populations in monolayer cultures with exogenous recombinant SHH stimulated cell proliferation. Together, the data provide clear evidence that Shh is synthesized by dental epithelium, reaches the underlying mesenchyme, and appears to act as an autocrine mitogen for epithelial cells and a paracrine mitogen for mesenchymal cells, thus exerting crucial functions in tooth germ growth, morphogenesis, and tissue-tissue interactions of bell stage of odontogenesis.

AB - Epithelial-mesenchymal interactions are required for tissue growth and gene expression patterns during odontogenesis. We showed previously that Sonic hedgehog (SHH) is detectable in both dental epithelium and mesenchyme, while Shh transcripts are present in dental epithelium only, suggesting that SHH functions as an autocrine signal in epithelium and a paracrine signal in mesenchyme. This hypothesis was tested here. We found by in situ hybridization that the SHH autocrine receptor Ptch-2 is indeed expressed in dental epithelium whereas the paracrine receptor Ptc is expressed in mesenchyme. Bovine bell stage tooth germs were microsurgically separated into epithelial and mesenchymal portions and the resulting tissue fragments were organ-cultured. In epithelium fragments cultured by themselves, gene expression of Shh and Gli-1 (a putative transcriptional mediator of hedgehog signaling) was significantly decreased in both inner dental epithelium and stratum intermedium layers; this was accompanied by a sharp drop in epithelial cell proliferation. However, in companion control tissue fragments containing both epithelium and mesenchyme, Shh and Gli-1 expression as well as cell proliferation were maintained. Treatment of dental epithelial or mesenchymal cell populations in monolayer cultures with exogenous recombinant SHH stimulated cell proliferation. Together, the data provide clear evidence that Shh is synthesized by dental epithelium, reaches the underlying mesenchyme, and appears to act as an autocrine mitogen for epithelial cells and a paracrine mitogen for mesenchymal cells, thus exerting crucial functions in tooth germ growth, morphogenesis, and tissue-tissue interactions of bell stage of odontogenesis.

KW - Cell proliferation

KW - Gli-1

KW - Inner dental epithelium

KW - Odontogenesis

KW - Patched

KW - Sonic hedgehog

KW - Stratum intermedium

UR - http://www.scopus.com/inward/record.url?scp=0037240612&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037240612&partnerID=8YFLogxK

M3 - Article

C2 - 12952180

AN - SCOPUS:0037240612

VL - 44

SP - 92

EP - 96

JO - Connective Tissue Research

JF - Connective Tissue Research

SN - 0300-8207

IS - SUPPL. 1

ER -