Bone morphogenetic proteins in teleost tooth development and evolution.

摘要

Bone Morphogenetic Proteins, or Bmps, are signaling molecules which play important roles in vertebrate embryogenesis and organogenesis. During the development of organs, Bmps are often expressed in complex, reiterated patterns. The function of these expression patterns continues to be elucidated, but Bmps can have both inductive and repressive effects on organ development. Changes in Bmp expression patterns are also implicated in the evolution of organs, including the beaks of Darwin's finches, the wings of bats, and a toothless gap in the rodent dentition. Bmp expression patterns are well-described during the development of the rodent dentition, and have been proposed to function in both limiting the sites where teeth can develop as well as inducing the expression of genes crucial for tooth development to progress. Genes required for the induction of complex Bmp expression patterns in teeth are unknown. This dissertation describes the expression, function, and regulation of Bmps during early tooth development of teleost fish embryos. Studying two teleost species, the zebrafish (Danio rerio) and the Mexican tetra (Astyanax mexicanus) allows several comparisons to be made which shed light on the role of Bmps in the evolution of teeth.; Complex, reiterated expression patterns of Bmps found in teleost teeth are generally conserved with those of the mouse, indicating that Bmps may be deployed in a similar manner in tooth development of all vertebrates. Subtle differences in Bmp expression were found between teleost fishes and mouse, between teleost fish species, and between tooth-forming regions within fish species, indicating possible evolutionary divergence. A striking lack of Bmp expression was discovered in the toothless mouth of the zebrafish, implicating this signaling pathway in an evolutionary loss of teeth characteristic of the zebrafish lineage. Experiments perturbing Bmp function in the toothed zebrafish pharynx indicate that Bmp expression is required to permit tooth development past the stage of initiation, although the developmental stages and tissues mediating this requirement remain unclear. Additionally, Bmp signaling from the nondental endoderm is required for normal spacing of teeth within the pharynx. Finally, experiments investigating potential upstream regulators of Bmps indicate for the first time that Fgf signaling is required to permit normal Bmp expression in teeth. These experimental findings are consistent with the hypothesis that Fgf-mediated changes in Bmp expression may have contributed to the evolutionary loss of teeth in the zebrafish, although a causal link has not been identified. Furthermore, Fgf-independent changes in zebrafish Bmp expression suggest that multiple changes in the genetic control of tooth development underlie this evolutionary event.