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The role of BMP-2 and TGF-beta during early development and patterning of the avian mandible and limb buds.

Date

1999

Authors

Kolodziejczyk, Steven Michael.

Journal Title

Journal ISSN

Volume Title

Publisher

Dalhousie University

Abstract

Description

The TGF-beta superfamily of growth factors is important to the proper development and differentiation of organisms. The molecules themselves are highly conserved between phyla and are found in virtually all organisms studied. During embryogenesis, superfamily members are implicated in cell and tissue differentiation directly and as components of a larger signal cascade ultimately leading to the production of a fully formed organism. They are suggested as candidate inductive molecules, supplying the information that will specify cell type and eventually lead to tissue formation. TGF-beta and BMP-2 are also of great importance in the adult and continue to be expressed throughout the life of the organism. The role of these molecules during very early development, however, is not completely understood.
The chick mandible and limb bud are similar in many respects. Each begins as a mass of undifferentiated mesenchyme overlain by epithelium. From these beginnings, two very different structures form. Members of the TGF-beta superfamily localize to both regions of the embryo early in development. To determine the distribution and role of these proteins, as well as their function is the aim of this study. By first establishing the presence of BMP-2 and TGF-beta, both superfamily members, in the chick limb and mandible, and then by inhibiting the function of the cytokines with neutralizing antibodies, it was hoped to learn about their importance during embryogenesis.
It appears that both factors are required to initiate and maintain pattern formation and regulate growth in both early mandible and limb bud. Both TGF-beta and BMP-2 are found in the developing limb and mandiblular primordium. Both factors are detectable throughout the developmental stages studied. In addition, their appearance in other regions of the chick during embryogenesis reinforce their developmental importance. Furthermore, the removal of the protein by antibody neutralization has profound effects upon development of limb and mandible, resulting in aberrant growth in antibody injected embryos. Limb and mandibular explants subjected to treatment with TGF-beta or BMP-2 neutralizing antibodies grow significantly taller than untreated controls, indicating a growth regulatory role for both factors. Explants treated with the highest doses of either TGF-beta or BMP-2 antibody exhibit skeletogenesis earlier than controls, as measured by HBQ staining. This suggests that, in addition to guiding early patterning in the limb and mandible, these factors may play a new role later in the developmental program and direct formation of cartilage and bone in the embryo.
Thesis (Ph.D.)--Dalhousie University (Canada), 1999.

Keywords

Biology, Anatomy., Biology, Cell., Biology, Animal Physiology.

Citation