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Timing cell cycles in multicellular development

Project description

Cell cycle regulation during development

Tissue architecture and organ size are determined during development in a precisely timed manner that requires careful orchestration of the cell cycle. Understanding the mechanisms underlying the temporal association of cell cycle and development is central to comprehending organ development. The EU-funded DevCycle project will use the nematode Caenorhabditis elegans as a model organism to study cell cycle during development. Researchers will create a novel microfluidics platform to image larval development with a focus on intestinal cells. Identification of novel regulators that control stage-specific gene expression will provide unprecedented insight into tissue-specific division patterns.

Objective

Animal development depends on precisely timed cell divisions, which ensure the formation of tissues and organs with specific architectures and functions. As cells differentiate and mature, they need to modify the expression of cell-cycle regulators in order to achieve tissue-specific division patterns. It is largely unknown how cells coordinate cell-cycle gene expression changes with developmental timing and how cell cycles can be altered to give rise to different tissue architectures and organ sizes.

DevCycle will address these questions by studying intestinal cell cycles in nematodes. I have recently pioneered tools to measure mRNA expression changes and chromatin modifications in purified intestinal cells from C. elegans, which we will use to uncover how the expression of cell-cycle genes is changing during development and to identify novel regulators that control stage-specific gene expression. Moreover, I will implement a novel microfluidics platform for long-term imaging of larval development to identify the mechanisms that allow temporal coupling of cell cycle and development. This system will allow us to visualize and manipulate transcription factor gradients that direct intestinal cell cycles, providing unprecedented insights into how cell cycles are timed. Finally, I will analyse the mechanisms that control cell-cycle behaviour in P. redivivus, a related nematode in which intestinal cells undergo a slightly different cell-cycle pattern. Expanding our analyses to this species will empower us to investigate how cell-cycle patterns can diversify to generate phenotypic variability.

Together, this research program will develop a mechanistic understanding of the temporal control of cell cycles in development, revealing new paradigms on how tissue-specific division patterns arise. This knowledge will open up future avenues to modulate cell cycles for tissue engineering purposes, as well as to control cell divisions in disease.

Host institution

KONINKLIJKE NEDERLANDSE AKADEMIE VAN WETENSCHAPPEN - KNAW
Net EU contribution
€ 1 500 000,00
Address
KLOVENIERSBURGWAL 29 HET TRIPPENHUIS
1011 JV AMSTERDAM
Netherlands

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Region
West-Nederland Noord-Holland Groot-Amsterdam
Activity type
Research Organisations
Links
Total cost
€ 1 500 000,00

Beneficiaries (1)