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Imaging vertebrate neural tube development

Project supervisor – James Briscoe

Division of Developmental Biology

The complex tissues and organs of every multicellular organism develop in a precise and reproducible manner from initially indistinguishable cells. A fundamental question is how such equipotent cells acquire the identity appropriate for their location. Perhaps the ultimate example of this is the vertebrate central nervous system where the generation of an extraordinary array of neurons with distinct properties and functions is required for the assembly of neuronal circuits. In many developing tissues, including the CNS, naïve cells interpret graded signals, termed morphogens, as positional cues that organize the pattern of cellular differentiation. Our goal is to understand the molecular and cellular mechanisms controlling this process.

In ventral regions of the CNS, the secreted protein Sonic Hedgehog (Shh) acts as a morphogen to induce five progenitor domains in precise spatial order in the neural tube. Each progenitor domain is distinguished by the expression of different combinations of transcription factors and each domain generates a distinct neuronal subtype. At the same time as cells acquire their molecular identity the tissue is growing in size due to proliferation and differentiation. We would like to understand how growth and patterning are coordinated. To address this, the project will use in vivo and in vitro approaches to image and track cells in the growing neural tube. These data will be incorporated into a quantitative model of the neural tube that we are building. The student will take advantage of several transgenic mouse lines, chick in vivo electroporation and imaging will be carried out using our regular and two-photon confocal microscopes.

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