Jan Huisken

Quantitative microscopy of zebrafish organogenesis

Previous and current research

The overall goal of the newly formed lab is the systematic study of developmental processes in living organisms by noninvasive biomedical imaging techniques such as optical microscopy. Of primary interest is the investigation of organogenesis in zebrafish with special emphasis on the function and morphogenesis of the cardiovascular system. We develop novel quantitative microscopy tools and experimental strategies to understand and describe tissue dynamics on a cellular level. High-speed fluorescence microscopy is the primary tool to capture the dynamics of a heartbeat and the fate of single cells during organogenesis. We address all experimental steps from innovative transgenic lines and microscope development to systematic image processing.

One of the technologies that are being developed is selective plane illumination microscopy (SPIM). This fluorescence microscopy technique uses a focused light-sheet to illuminate the specimen from the side. SPIM achieves excellent resolution at high penetration depths while being minimally invasive at the same time. SPIM offers a number of advantages over established techniques such as strongly reduced photo-bleaching, high dynamic range, and high acquisition speed. The translucent nature of the zebrafish embryo allows for observation of the heart and the whole cardiovascular system in the living animal. Optical manipulation tools like photo-convertible fluorophores, photo-activatable ion-channels, and laser nanosurgery are used in addition to image acquisition.

The lab takes a truly interdisciplinary approach. Scientists with various backgrounds collaborate and develop novel experimental strategies to achieve a common goal.

Left: The concept behind fluorescence light-sheet microscopy. Right: High-speed mSPIM video sequence of a transgenic fish expressing fluorescent proteins in the endocardium [Tg(flk1:GFP)s843], myocardium [Tg(cmlc2:DsRed)s879] and blood [Tg(gata1:DsRed)sd2].

Future prospects and goals

- multi-dimensional reconstruction of the zebrafish heart during development
- detailed dynamic map of the vascular system, annotated with blood flow parameters
- development of the next generation SPIM
- multi-dimensional visualization to study embryo to embryo differences
- regenerative processes in the cardiovascular system

About

2000-2004: PhD work at EMBL-Heidelberg, PhD in Physics, University of Freiburg 2004-2005: Postdoctoral work at the EMBL-Heidelberg 2005-2009: Postdoctoral work at the University of California, San Francisco since 2010: Research Group Leader at the Max Planck Institute of Molecular Cell Biology and Genetics

Selected publications

Herbert et al. Arterial-Venous Segregation by Selective Cell Sprouting: An Alternative Mode of Blood Vessel Formation. Science (2009) vol. 326 (5950) pp. 294-298

Huisken and Stainier. Selective plane illumination microscopy techniques in developmental biology. Development (2009) vol. 136 (12) pp. 1963-75

Scherz et al. High-speed imaging of developing heart valves reveals interplay of morphogenesis and function. Development (2008) vol. 135 (6) pp. 1179-87

Huisken and Stainier. Even fluorescence excitation by multidirectional selective plane illumination microscopy (mSPIM). Opt Lett (2007) vol. 32 (17) pp. 2608-10

Huisken et al. Optical sectioning deep inside live embryos by selective plane illumination microscopy. Science (2004) vol. 305 (5686) pp. 1007-9

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