Projects in Developmental Cell Biology
- Project 1
- Project 2
- Project 3
(1) Cytokinesis in Development and Differentiation:
We study the differential regulation of cytokinesis as a model for a conserved cellular process under developmental control using the C. elegans embryo and mammalian cell culture models: Morphogenesis and differentiation are accompanied by dramatic shape changes of cells. However, one of the most extreme cell shape changes occurs during each cell division. In the context of a tissue, each cell division causes a distortion of the local cellular pattern, which can either be resolved by dynamic restoration or can result in morphogenesis and differentiation. While it has become clear that the differential regulation of mitotic processes plays a crucial role here, evidence is accumulating that the differential regulation of cytokinesis is equally important: We could demonstrate that left-right symmetry breaking in C. elegans is timed by cytokinesis, which acts as a developmental clock and as an unexpected signaling mechanism. More recently, we could show that symmetry breaking during formation of the dorsal-ventral axis uses the remnant of the first cell division as polarity landmark.
Our future goals are to identify the developmental roles of cytokinesis and the underlying tissue-specific regulation. This will allow us to define different modes of cytokinesis and how they feedback onto morphogenesis and differentiation.
Figure: Differential use of the midbody as a polarizing element in spindle orientation in wild-type (left, only the posterior cell uses the midbody remnant for spindle roation), par-2 (middle, none of the cell uses the midbody remnant) and par-6 (both cells use the midbody remnant).
(2) Developmental Functions of Autophagy:
The individual roles of autophagy and metabolic pathways in cell differentiation and tumorigenesis are incompletely understood. Therefore, the aim of this project is to use a simple metazoan to systematically untangle roles of autophagy and metabolism in differentiation and tumor formation. To achieve this, we use a C. elegans germline tumor in which tumor cells undergo spontaneous trans-differentiation into somatic cell types. Like this, cell differentiation is no longer coupled to development of the organism, yet, stochastically or through forced expression of fate-determining transcription factors, most final cell types are generated. We exploit this system and use transcriptomics, proteomics, high-content imaging and automated image analysis to identify how changes in autophagy and metabolism affect gene regulatory networks of cells differentiating into specific cell types on the mRNA, protein and phenotype level. This will allow us to answer which metabolic pathway affects a specific differentiation program and how this pathway affects tumorigenesis.
Figure: The germline tumor model in C. elegans (top) and induction of autophagy during germline tumor growth and differentiation (bottom).
(3) Head morphogenesis:
We use head formation in C. elegans as a model to study a complex morphogenetic process. Head morphogenesis relies on a cooperation between sensory organ, nervous system, foregut, mouth, and muscle morphogenesis to assemble a coherent organs system. We have successfully developed an integrated platform that allows us to analyse head formation quantitatively at single-cell resolution. This platform consists of high-resolution time-lapse microscopy, automated cell tracking, and segmentation. We combine this with genetics and micromanipulations to decompose newly identified morphogenetic processes into their underlying molecular and cellular mechanisms.
Our long-term goal is to describe intertwined organogenesis quantitatively as a dynamically evolving network that unites genetic regulation and cellular interactions. We therefore collaborate with the group of Matthias Kaschube to perform automated cell segmentation (https://fias.uni-frankfurt.de/neuro/kaschube). With this collaborative approach we recently became part of the DFG Research Unit FOR 1756 'Functional dynamics of cell contacts in cellular assemblies and migratory cells' (http://for1756.uni-goettingen.de).
Figure: Invariant development enables us to perform multi-parametric analysis, e.g. we can align time-lapse microscopy data using markers for different structures or tissues.
Electron Microscopy of Photostimulated Chemical Synapses
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