Expression profiling of transforming growth factor beta superfamily genes in developing orofacial tissue

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.