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Anbmp2/4 is a new member of the transforming growth factor-beta superfamily isolated from a crinoid and involved in regeneration.

ABSTRACT: Invertebrates have frequently been used to help understand the complexities of regulatory gene function and evolution. The bone morphogenetic proteins (BMPs) are a highly conserved group of secreted regulatory factors that play an important part in early embryonic patterning. In the present study we have used the remarkable regenerative potential of crinoid echinoderms to explore the BMPs' site of expression in an adult developmental programme. Our results suggest that a crinoid BMP2/4 homologue is actively involved during the early stages of blastemal regeneration at a time when fundamental patterns are being established. This supports the idea of an evolutionary developmental programme where essential gene families are conserved throughout phylogeny in terms of both expression and function.

SUBMITTER: Patruno M

PROVIDER: S-EPMC1691383 | biostudies-other | 2003 Jul

REPOSITORIES: biostudies-other

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Anbmp2/4 is a new member of the transforming growth factor-beta superfamily isolated from a crinoid and involved in regeneration.

Patruno M M McGonnell I I Graham A A Beesley P P Candia Carnevali M D MD Thorndyke M M

Proceedings. Biological sciences 20030701 1522

Invertebrates have frequently been used to help understand the complexities of regulatory gene function and evolution. The bone morphogenetic proteins (BMPs) are a highly conserved group of secreted regulatory factors that play an important part in early embryonic patterning. In the present study we have used the remarkable regenerative potential of crinoid echinoderms to explore the BMPs' site of expression in an adult developmental programme. Our results suggest that a crinoid BMP2/4 homologue ...[more]

PMID: 12965024

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Project description:Numerous signaling molecules have been shown to participate in the dynamic process of orofacial development. Among these signal mediators, members of the transforming growth factor beta (TGFbeta) superfamily have been shown to play critical roles. Developing orofacial tissue expresses TGFbeta and bone morphogenetic protein (BMP) mRNAs, their protein isoforms and TGFbeta- and BMP-specific receptors. All these molecules display unique temporospatial patterns of expression in embryonic orofacial tissue, suggesting functional roles in orofacial development. For example, the TGFbetas and BMPs regulate maxillary mesenchymal cell proliferation and extracellular matrix synthesis. This is particularly noteworthy in that perturbation of either process results in orofacial clefting. Although the cellular and phenotypic effects of the TGFbeta superfamily of growth factors on embryonic orofacial tissue have been extensively studied, the specific genes that function as effectors of these cytokines in orofacial development have not been well defined.In the present study, oligonucleotide-based microarray technology was utilized to provide a comprehensive analysis of the expression of the panoply of genes related to the TGFbeta superfamily, as well as those encoding diverse groups of proteins functionally associated with this superfamily, during orofacial ontogenesis.Of the 7000 genes whose expression was detected in the developing orofacial region, 249 have been identified that encode proteins related to the TGFbeta superfamily. Expression of some (27) of these genes was temporally regulated. In addition, several candidate genes, whose precise role in orofacial development is still unknown, were also identified. Examples of genes constituting this cluster include: TGFbeta1-induced antiapoptotic factor-1 and -2, TGFbeta-induced factor 2, TGFbeta1 induced transcript-1 and -4, TGFbeta-inducible early growth response 1, follistatin-like 1, follistatin-like 3, transmembrane protein with EGF-like and two follistatin-like domains (Tmeff)-1 and -2, nodal modulator 1, various isoforms of signal transducers and activators of transcription (Stat), notch, and growth and differentiation factors.Elucidation of the precise physiological roles of these proteins in orofacial ontogenesis should provide unique insights into the intricacies of the TGFbeta superfamily signal transduction pathways utilized during orofacial development.

Project description:Axolotls (urodele amphibians) have the unique ability, among vertebrates, to perfectly regenerate many parts of their body including limbs, tail, jaw and spinal cord following injury or amputation. The axolotl limb is the most widely used structure as an experimental model to study tissue regeneration. The process is well characterized, requiring multiple cellular and molecular mechanisms. The preparation phase represents the first part of the regeneration process which includes wound healing, cellular migration, dedifferentiation and proliferation. The redevelopment phase represents the second part when dedifferentiated cells stop proliferating and redifferentiate to give rise to all missing structures. In the axolotl, when a limb is amputated, the missing or wounded part is regenerated perfectly without scar formation between the stump and the regenerated structure. Multiple authors have recently highlighted the similarities between the early phases of mammalian wound healing and urodele limb regeneration. In mammals, one very important family of growth factors implicated in the control of almost all aspects of wound healing is the transforming growth factor-beta family (TGF-beta). In the present study, the full length sequence of the axolotl TGF-beta1 cDNA was isolated. The spatio-temporal expression pattern of TGF-beta1 in regenerating limbs shows that this gene is up-regulated during the preparation phase of regeneration. Our results also demonstrate the presence of multiple components of the TGF-beta signaling machinery in axolotl cells. By using a specific pharmacological inhibitor of TGF-beta type I receptor, SB-431542, we show that TGF-beta signaling is required for axolotl limb regeneration. Treatment of regenerating limbs with SB-431542 reveals that cellular proliferation during limb regeneration as well as the expression of genes directly dependent on TGF-beta signaling are down-regulated. These data directly implicate TGF-beta signaling in the initiation and control of the regeneration process in axolotls.

Dataset Information

Anbmp2/4 is a new member of the transforming growth factor-beta superfamily isolated from a crinoid and involved in regeneration.

Publications

Anbmp2/4 is a new member of the transforming growth factor-beta superfamily isolated from a crinoid and involved in regeneration.

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