Image-Based Structural Modeling of the Early-Stage Zebrafish Embryo Brain

Abstract

During embryogenesis, spatiotemporal gene expression patterns direct the segmentation of primary brain compartments that are progressively refined into functional subunits of the adult brain. At the midbrain-hindbrain boundary (MHB), early errors in gene expression result in structural malformations that impair, by an unknown mechanism, the subsequent functional development of the tectum, cerebellum, and tegmentum which help to coordinate visuomotor responses. A quantitative model of the dynamic relationship between gene expression and structure formation would shed further insight on the role of different genes in this process. However, time-series analysis of the 3-dimensional multiphoton microscopy images of early-stage zebrafish embryo brain primordia poses a distinct challenge since the brain initially lacks recognizable landmarks to use as reference. Additional difficulty arises due to noise and pixel intensity variations within and across image data sets. To address these difficulties, we have developed a computational method that assigns simple geometric elements such as “beads” and “bonds” in a hierarchically refined structural model of the zebrafish brain for comparing different phenotypes and developmental time points. Our measurement highlight morphological differences between the wild type and zebrafish fgf8a(acerebellar) mutant that does not form MHB. Our approach is applicable to building quantitative surface models for images of other systems.