Rinaldin: Cellular organization in development

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The Rinaldin group uses quantitative biology approaches to understand how cellular structures form and adapt during the development of multicellular organisms.

Across all scales, multicellular systems are highly organized. Molecules, biochemical activities, and cells interact to generate emergent structures that collectively enable life to function. These organizational processes are clearly observed in embryonic development, where from a single egg, molecules self-organize into cells that become tissues, and ultimately organs. How does the organization of the cellular machinery emerge and adapt to achieve robust yet flexible development? To address this question, our group uses an interdisciplinary approach that integrates physical and biochemical techniques. We use eggs and embryos of X. laevis frogs and zebrafish as model systems. We build on comparative biology with further organisms to understand how developmental programs evolve and how the underlying cellular machinery adapts to maintain cellular homeostasis across species.

Compartmentalization in multinucleated systems

Many embryos start their development consisting of a shared cytoplasm where multiple nuclei coexist, a multinucleated state. This state lacks cellular membranes, requiring therefore different mechanisms to separate the cell content. We have for example recently discovered that properties of growth of microtubule asters define the boundaries, stability, and organization strategies of compartments in the cytoplasm.

 

From left to right: (a) Schematic diagram of a cytoplasmic compartments. (b) Fluorescence image of microtubule asters, actin, and mitochondria in early zebrafish embryos. (c) Cytoplasmic organization strategies of early embryos depending on the amount of microtubule branching. Adapted from Rinaldin et al., XXX.

Development and maintenance of multicellularity

Across biology, there is an evolutionary drive towards multicellularity, yet at the same time multicellularity is often “lost” in diseases (cancer, liver diseases, etc…) and tissue formation, and multicellular tissues become multinucleated. We are interested in uncovering the mechanistic principles that govern these transitions and ultimately learn how to control them to prevent disease. We focus our investigation on the microtubule cytoskeleton and cell membrane, structures critical for cytoplasmic and cellular organization.

 

Left: Cytoplasmic compartments in interphase-arrested X. laevis frog egg cytoplasm undergoing microtubule aster invasion and coarsening of cytoplasmic compartments. Adapted from Rinaldin et al., XXX. Right: The transitions between multinucleated and multicellular states across biology.

Multinucleated and multicellular states in morpho- and organo-genesis

In zebrafish embryonic development, most tissues are organized as multicellular structures, but certain regions form multinucleated states that support key processes such as axis specification and heart formation. How do the distinct organizational properties of multinucleated versus multicellular states affect signaling and morphogenesis? We aim to understand how embryos exploit both architectures to achieve robust and adaptable patterning.

 

Fluorescence microscopy image of an entire zebrafish embryo (left) and zoomed in view of multicellular and multinucleated regions.