Scaling of Dorsal/Ventral patterning by BMPs in developing zebrafish embryos.
Yan Huang1, Francesca Tuazon2, Joseph M Zinski2, Mary C Mullins2, David M Umulis1. 1) Purdue University, West Lafayette, IN; 2) University of Pennsylvania, Philadelphia, PA.
Scale invariance in pattern formation is a phenomenon that occurs when the patterns and organization of tissues, organs or overall organisms remain proportionate with the overall size of the domain or organism. Scale invariance has been observed in numerous contexts including homologous patterning processes that are observed between: 1) individuals within the same species (intraspecies), 2) between different species (interspecies), or 3) between different temporal stages during the development of a domain changing over time (e.g. growth) in an individual (dynamic). Herein we focus on interspecies and intraspecies scale invariance of the dorsal/ventral (DV) patterning during early embryonic development of zebrafish. The DV axis is patterned by a gradient of Bone Morphogenetic Protein (BMP) signaling with a maximum ventrally and a minimum dorsally. Our preliminary data show that embryos with margin circumference reduced surgically by up to 20% are able to grow into the wild-type phenotype and the corresponding BMP gradient scales with normal-size embryos. To elucidate mechanisms explaining these results, we dissected the full extracellular BMP regulatory network into 3 sub-motifs (blastula, Sizzled and ADMP) and developed partial differential equation (PDE) models for each motif. Parameters that are not well-defined by literature (production, binding, degradation) were screened first with the shape of the BMP gradient obtained from previous studies and then with scaling. At steady state, simulation results show that the Sizzled motif is able to scale while the blastula and ADMP motifs fail to scale, contrary to what has been investigated with respect to ADMP’s role with the scaling mechanism recently reported in Xenopus. Based on these, we hypothesize that Sizzled and feedback control are key motifs for scale invariance. To validate our hypothesis, we are going to make mutants of extracellular BMP regulators and check scaling among different sized embryos. We are also going to test interspecies scaling of BMP gradient among zebrafish and other species such as giant danio. The results from this research will enable us to identify the mechanism of intraspecies and interspecies scaling, to shed light on dynamic scale invariance, and to better understand the earliest stages of life in quantitative detail, specifically, the regulation of BMP signaling.