RESUMEN
Theory is a critical component of the biological research process, and complements observational and experimental approaches. However, most biologists receive little training on how to frame a theoretical question and, thus, how to evaluate when theory has successfully answered the research question. Here, we develop a guide with six verbal framings for theoretical models in biology. These correspond to different personas one might adopt as a theorist: 'Advocate', 'Explainer', 'Instigator', 'Mediator', 'Semantician' and 'Tinkerer'. These personas are drawn from combinations of two starting points (pattern or mechanism) and three foci (novelty, robustness or conflict). We illustrate each of these framings with examples of specific theoretical questions, by drawing on recent theoretical papers in the fields of ecology and evolutionary biology. We show how the same research topic can be approached from slightly different perspectives, using different framings. We show how clarifying a model's framing can debunk common misconceptions of theory: that simplifying assumptions are bad, more detail is always better, models show anything you want and modelling requires substantial maths knowledge. Finally, we provide a roadmap that researchers new to theoretical research can use to identify a framing to serve as a blueprint for their own theoretical research projects.
Asunto(s)
Biología , Modelos Teóricos , Proyectos de Investigación , Evolución BiológicaRESUMEN
Myocyte enhancement factor 2C (MEF2C) is a transcription factor studied in the development of skeletal and smooth muscles. Bone resorption studies have exhibited that the reduced expression of MEF2C contributes to osteopetrosis and the dysregulation of pathological bone remodeling. Our current study aims to determine how MEF2C contributes to osteoclast differentiation and to analyze the skeletal phenotype of Mef2c-cKO mice (Cfms-cre; Mef2cfl/fl). qRT-PCR and Western blot demonstrated that Mef2c expression is highest during the early days of osteoclast differentiation. Osteoclast genes, including c-Fos, c-Jun, Dc-stamp, Cathepsin K, and Nfatc1, had a significant reduction in expression, along with a reduction in osteoclast size. Despite reduced CTX activity, female Mef2c cKO mice were osteopenic, with decreased bone formation as determined via a P1NP ELISA, and a reduced number of osteoblasts. There was no difference between male WT and Mef2c-cKO mice. Our results suggest that Mef2c is critical for osteoclastogenesis, and that its dysregulation leads to a sex-specific osteopenic phenotype.