How do the organs of a growing organism reach their correct size? Tissue growth and the formation of diverse cell types are coordinated to generate organs of appropriate size and structure during development.

The Kicheva group is studying how this coordination takes place in the vertebrate neural tube, which is the embryonic precursor of the spinal cord and the brain.

Along the dorsoventral (DV) axis of the spinal cord, highly dynamic morphogen signaling gradients regulate the activity of the downstream regulatory network that controls pattern formation. This results in the specification of multiple progenitor domains arranged in precise stripes along the DV axis. These morphogen pathways are also implicated in controlling neural progenitor proliferation and terminal differentiation into defined neuron subtypes.

However, when and how morphogen signals control these temporally dynamic processes is poorly understood. We aim to understand how cells interpret morphogen signaling to regulate their rates of proliferation and terminal differentiation.

We will focus on the temporal aspects of the process, building on our previous findings that showed that morphogen signaling as well as cell cycle progression parameters undergo significant changes in the first three days of mouse spinal cord development. We will also investigate how opposing morphogen pathways work synergistically to regulate the spatiotemporal dynamics of proliferation and differentiation at the cellular and tissue level.  We will also begin investigating the molecular mechanism by which morphogen signaling is linked to the cell cycle machinery.

To address these questions, we will develop quantitative ex vivo and in vivo assays in which we take advantage of chick explant culture, neural tube organoids, lineage tracing using the MADM technique, as well as genomic approaches. We will collaborate with the Tanaka, Hippenmeyer and von Haeseler groups on different aspects of the project.

We anticipate that this project will generate high-resolution quantitative data that will help achieve a better understanding of the coordination between patterning and growth and the regulation of tissue size. In the long term, our findings will open possibilities to further study the common principles of pattern and size regulation between the spinal cord and the brain, as well as between development and regeneration.

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