Dynamic analysis of the expression of the TGFbeta/SMAD2 pathway and CCN2/CTGF during early steps of tooth development

Marcos S Pacheco1, Alice H Reis, Diego P Aguiar

  • 1Departamento de Anatomia, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.

Cells, Tissues, Organs
|December 20, 2007
PubMed
Abstract

Insights

Cellular communication factor CCN2 (Connective tissue growth factor) and transforming growth factor beta (TGF-β)/SMAD2/3 signaling are active during tooth development. However, they appear to function independently in regulating cell proliferation in developing mouse teeth.

Area of Science:

  • Developmental Biology
  • Cell Signaling
  • Molecular Biology

Background:

  • Connective tissue growth factor (CCN2) is present during tooth development.
  • The relationship between CCN2 and transforming growth factor beta (TGF-β)/SMAD2/3 signaling in early tooth development is not well understood.

Purpose of the Study:

  • To compare the expression of CCN2 and TGF-β/SMAD2/3 pathway components during tooth development.
  • To analyze the function of TGF-β/SMAD2/3 signaling in wild-type (WT) and Ccn2 null (Ccn2-/-) mice.

Main Methods:

  • Immunoreaction of coronal sections from WT and Ccn2-/- mice at embryonic days E11.5-E18.5.
  • Detection of CCN2, TGF-β signaling components (TGF-β1, TGF-β receptor II, SMADs2/3, SMAD4).
  • Assays for 5'-bromo-2'-deoxyuridine and proliferating cell nuclear antigen to assess cell proliferation.

Main Results:

  • CCN2 and TGF-β signaling components were expressed in tooth development signaling centers.
  • Cell proliferation patterns differed between epithelial and mesenchymal cells during development.
  • No correlation was found between TGF-β1 cascade function and CCN2 expression in Ccn2-/- mice, with no changes in SMAD2 phosphorylation or cell proliferation.

Conclusions:

  • CCN2 and TGF-β/SMAD2/3 signaling are active in dynamic signaling centers during tooth development.
  • These two mechanisms appear to operate independently in the context of tooth development.

Related Concept Videos

TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors are of three kinds RI, RII, and RIII. The RI...
Hedgehog Signaling Pathway02:33

Hedgehog Signaling Pathway

The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...
Determination01:51

Determination

During embryogenesis, cells become progressively committed to different fates through a two-step process: specification followed by determination. Specification is demonstrated by removing a segment of an early embryo, “neutrally” culturing the tissue in vitro—for example, in a petri dish with simple medium—and then observing the derivatives. If the cultured region gives rise to cell types that it would normally generate in the embryo, this means that it is specified. In contrast, determination...
Non-Canonical Wnt Signaling Pathways01:41

Non-Canonical Wnt Signaling Pathways

Wnt is a zygotic effect gene that is expressed during very early embryonic development. It regulates various processes in animals starting from early development through the adult stage, such as organogenesis in the embryo and maintenance of neuronal and blood stem cells. Wnt proteins can induce a wide variety of intracellular pathways depending upon the specific abilities of different Wnt ligands to form a complex with shared and cognate receptors in the presence of different co-receptors. The...
Canonical Wnt Signaling Pathway02:54

Canonical Wnt Signaling Pathway

The gene encoding the main signaling molecules of the Wnt signaling pathways (the Wnt proteins) was discovered almost four decades ago by Nüsslein-Volhard and Wieschaus. They identified and originally named the gene "wingless" (wg) after a phenotype discovered during their landmark genetic screen in Drosophila for body pattern defects. At around the same time, another researcher named Harold Varmus found that a murine tumor virus activates the mammalian wg homolog, Int-1, which results in tumor...