Mathematical modeling reveals cell differentiation processes and progenitor kinetics necessary for proper nephrogenesis

Introduction The developing zebrafish nephron contains a diverse repertoire of cell populations with intrinsically dynamic roles and interactions. Previous studies characterizing these populations have utilized genetic approaches based on powerful molecular methods, such as in situ hybridization, immunohistochemistry, and both live and fixed imaging. However, our understanding of the cellular characteristics of the populations necessary for renal development in the zebrafish model is lacking in comparison to our understanding of the genetic/ morphogenic drivers of nephron segmentation. Methods To investigate the potential drivers of nephron development from the population perspective, we incorporated traditional molecular tools for determining cellular characteristics as well as algorithmic based optimization methods. We synthesized multiple ODE based models to investigate hypotheses surrounding populations existing in early zebrafish nephron development. Results Our model based findings showed that deferential forms of fate processes may be necessary for zebrafish pronephros development. Also, we provide evidence for differentiated populations being the potential drivers of renal development rather than progenitor populations. Discussion Our findings further bring forward the idea that differentiated populations are vital for the growth and development at the single nephron level in the zebrafish model. We also continue the investigation of varied forms of fate being necessary in renal development.