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Open science: 4D digital atlas of vascular development[Bearbeiten]

Projektbeschreibung[Bearbeiten]

Abstract[Bearbeiten]

The vascular system provides cells with oxygen, nutrients, and is used by the immune system to monitor the state of the organism. Hence, it is not surprising that cardiovascular diseases are the main cause of death and disability in the world. Understanding vessel development and maintenance is therefore of high interest. Recently, zebrafish has been established as a powerful in vivo model for vascular research. The formation of the vasculature in zebrafish is highly dynamic and already after 24 hours of development, a functional network with a beating heart is established. Here, I propose to build an open access, browser based 4D (3D and time) atlas of the developing vasculature in zebrafish based on images acquired using selective plane illumination microcopy (SPIM). The atlas will provide unique insight into the dynamic formation of the vascular network with high temporal and spatial resolution. Additionally, as the atlas will contain the data of several fish, it will provide an estimate of the variation of the vasculature at any selected region and timepoint. This will help to correctly interpret perturbation experiments such as the analysis of mutations, drug screens or toxicity assays in comparison to the unperturbed case. As the proposed vascular atlas will be annotated, it will also be a good platform for educational purposes such as for biology courses. More generally, as I will document the generation of the 4D atlas in a step-by-step way, it will provide a role model for making large 3D image datasets accessible and hopefully encourage other scientists to follow this example.

Introduction and Overview[Bearbeiten]

Figure 1: 3D visualization of a whole embryo expressing a vascular marker (cyan, kdrl:EGFP) and a red blood cell marker (magenta, Gata1a:dsRed) with a zoom into one intersegmental vessel and its branching (scale bar 40 um).

The vascular system provides cells with oxygen, nutrients, and is used by the immune system to monitor the state of the organism. Hence, it is not surprising that cardiovascular diseases are the main cause of death and disability in the world [1]. Understanding vessel development and maintenance is therefore of high interest. Recently, zebrafish has been established as a powerful in vivo model for vascular research [2]. Already after 24 hours of development, a functional network with a beating heart is established. To understand the establishment of the vascular network in zebrafish and its dynamic properties, I have developed a custom-built imaging framework using selective plane illumination microscopy (SPIM). SPIM is a very gentle microscopy technique with minimized phototoxicity that enables long term acquisitions of healthy growing animals [3]. With SPIM, I imaged the development of the whole vascular network of several fish over the course of several days with high spatial and temporal resolution. The resulting datasets provide unique insight into the dynamic formation of the vascular network. As an open science fellow, I propose to build an open access, 4D (3D and time) digital atlas of zebrafish vascular development with annotations using the acquired image datasets.

A digital atlas to understand vascular development[Bearbeiten]

The proposed 4D atlas will provide a valuable resource for scientists to understand vascular development in 3D (Figure 1) over time. Its dynamic data will provide a unique source to understand the processes of network formation and remodelling due to vessel sprouting and pruning. 4D visualization, however, is a non-trivial task, especially as the acquired data is huge (up to 8 TB). As an open science fellow, I will work on the way to visualize my data relying on the recent development of new open source 3D visualization tools such as SciView [4], new data compression tools, and data formats such as hdf5 [5]. The resulting 4D atlas will be accessible online as an open science browser-based platform so that atlas user will be able to inspect and study the large datasets over the internet.

To complement the atlas with information from several embryos, I aim at implementing a tool so that the user can extract an estimate for the variation of the vasculature for any selected region and timepoint. Understanding the variation of the vascular network in the unperturbed, healthy growing zebrafish is important. It provides the basis for the correct interpretation of perturbation experiments such as the analysis of mutations, drug screens or toxicity assays, and their influence on the vasculature.


A role model for providing and sharing large image data[Bearbeiten]

Sharing large 3D image datasets and making them accessible in a browser has so far been a challenging and time-consuming task. With the proposed atlas, I will establish tools to facilitate this process and therefore the atlas will pave the way for sharing large 3D image datasets. I will complement the atlas with a detailed step-by-step description of how to transform a large dataset consisting of individual image stacks to an online, open access dataset. This will promote open science by reducing the barrier of sharing large datasets online.


A valuable source for education[Bearbeiten]

The 4D vascular atlas will be annotated so that the development of individual vascular plexuses and organs are highlighted. The annotations will be in German and English. With this, the atlas becomes a useful resource for education, targeted to a general audience. The atlas will therefore help in increasing the broad understanding of how dynamic developmental processes are, how the vascular system is established in a vertebrate organism such as the zebrafish, and how microscopy helps us to understand fundamental biological processes. Consequently, there will also be an explanation of the microscopy technique and its advantages for long term imaging so that the dataset can be reproduced by other researchers.


Conclusions[Bearbeiten]

The proposed vascular atlas will provide a unique resource of 4D vascular development. It will not only provide a valuable resource for researchers to understand dynamic processes and variation in the vasculature but also be a good platform for educational purposes such as in biology courses. As the generation of the 4D atlas will be documented in a step-by-step way, it will provide a role model for making large scale image data accessible and hopefully encourage other scientists to follow this example.

References[Bearbeiten]

  1. World Health Organization (2011). "Global Atlas on cardiovascular disease prevention and control". Ed. by S. Mendis, P. Puska, and B. Norrving
  2. Gore, Aniket V, Kathryn Monzo, Young R Cha, Weijun Pan, and Brant M Weinstein. 2012. “Vascular Development in the Zebrafish.” Cold Spring Harbor Perspectives in Medicine.
  3. Daetwyler, Stephan, and Jan Huisken. 2016. “Fast Fluorescence Microscopy with Light Sheets.” The Biological Bulletin 231 (1): 14–25.
  4. https://imagej.net/SciView
  5. https://support.hdfgroup.org/HDF5/whatishdf5.html


Contact information[Bearbeiten]

  • Name: Stephan Daetwyler
  • Institution: Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG)
  • Kontakt: daetwyle at mpi-cbg.de