Identification of adult mineralized tissue zebrafish mutants.

Zebrafish craniofacial, skeletal, and tooth development closely resembles that of higher vertebrates. Our goal is to identify viable adult zebrafish mutants that can be used as models for human mineralized craniofacial, dental, and skeletal system disorders. We used a large-scale forward-genetic chemical N-ethyl-nitroso-urea mutagenesis screen to identify 17 early lethal homozygous recessive mutants with defects in craniofacial cartilage elements, and 7 adult homozygous recessive mutants with mineralized tissue phenotypes including craniofacial shape defects, fused sutures, dysmorphic or missing skeletal elements, scoliosis, and neural arch defects. One mutant displayed both an early lethal homozygous phenotype and an adult heterozygous phenotype. These results extend the utility of the zebrafish model beyond the embryo to study human bone and cartilage disorders.

Rb1 mRNA expression in developing mouse teeth.

Rb1 is a tumor suppressor gene that regulates cell cycle progression through interactions with E2F transcription factors. In recent years, new roles for Rb1 in regulating cellular differentiation have also emerged. For example, it has been shown that Rb1 regulates osteoblast differentiation in a cell cycle independent manner, by binding to the transcription factor Runx2, and facilitating the up-regulation of late bone differentiation markers. Based on the facts that Runx2 also functions in tooth development, and that little is known about potential roles for Rb1 in mammalian tooth development, here we evaluated the expression of Rb1 mRNA in developmentally staged mouse teeth. Our data show that Rb1 mRNA is expressed in both dental epithelial and dental mesenchymal progenitor cells. In addition, Rb1 mRNA appears upregulated in differentiating ameloblasts and odontoblasts, suggesting roles for Rb1 in tooth differentiation.