Abstract
Threespine stickleback fish offer a powerful system to dissect the genetic basis of morphological evolution in nature. Marine sticklebacks have repeatedly invaded and adapted to numerous freshwater environments throughout the Northern hemisphere. In response to new diets in freshwater habitats, changes in craniofacial morphology, including heritable increases in tooth number, have evolved in derived freshwater populations. Using a combination of quantitative genetics and genome resequencing, here we fine-mapped a quantitative trait locus (QTL) regulating evolved tooth gain to a cluster of ten QTL-associated single nucleotide variants, all within intron four of Bone Morphogenetic Protein 6 (Bmp6). Transgenic reporter assays revealed this intronic region contains a tooth enhancer. We induced mutations in Bmp6, revealing required roles for survival, growth, and tooth patterning. Transcriptional profiling of Bmp6 mutant dental tissues identified significant downregulation of a set of genes whose orthologs were previously shown to be expressed in quiescent mouse hair stem cells. Collectively these data support a model where mutations within a Bmp6 intronic tooth enhancer contribute to evolved tooth gain, and suggest that ancient shared genetic circuitry regulates the regeneration of diverse vertebrate epithelial appendages including mammalian hair and fish teeth.
Highlights
Finding the genes and the mutations that drive the evolution of animal form remains an important goal in biology [1]
Recombinant chromosomes that increase tooth number compared to marine chromosomes suggest that the tooth controlling region of chromosome 21 lies within the benthic portion of the recombinant chromosome
Recombinant chromosomes one and three increased tooth number, each behaving like a benthic allele of chromosome 21 (P value from likelihood ratio test = 3.0 x 10−4 for both) (Fig 1B)
Summary
Finding the genes and the mutations that drive the evolution of animal form remains an important goal in biology [1]. Epithelial Bmp inhibits expression of Pax and Pitx, developmental markers of the forming tooth placode [9,10] These results suggest an inhibitory role of BMP signaling on tooth development. Mice with dental epithelial ablation of the BMP receptor, Bmpr1a, or transgenic for a construct overexpressing a BMP antagonist, Noggin, in dental epithelium have tooth arrest at the bud and placode stage, respectively [13,14]. Together, these results suggest that there are both activating and inhibitory roles of BMP signaling during tooth development. Polyphyodont vertebrates (e.g. sharks, teleosts, and reptiles) that continuously replace their teeth offer an opportunity to study the genetic and developmental basis of tooth regeneration [6]
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