MRC National Institute for Medical Research, London
Science for Health
This project is now closed
Development of the vertebrate nervous system
Project supervisor: James Briscoe (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 appropriate identity 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 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. Much less well understood is the gene regulatory programme in the dorsal neural tube. Secreted proteins of the BMP and Wnt family are involved but how these morphogens control the gene expression in dorsal progenitors to establish progenitor identity is not clear.
To address this, we will use a combination of in vivo experimental manipulation, including in ovo electroporation, FACS and RNA-seq together with in silico analysis to systematically decipher and model the neural tube network. The function of factors identified by these approaches will be examined and used to build, challenge and refine the model of neural tube development. The identification of the players and their functions within the network will offer insight into the mechanisms and principles controlling neural tube development.
References
- Balaskas, N; Ribeiro, A; Panovska, J; Dessaud, E; Sasai, N; Page, Karen M; Briscoe, J and Ribes, V (2012)
Gene regulatory logic for reading the Sonic Hedgehog signaling gradient in the vertebrate neural tube.
Cell 148, 273-284 PubMed abstract - Bushati, N and Briscoe, J (2012)
Regulation of Neuronal Subtype Identity in the Vertebrate Neural Tube (Neuronal Subtype Identity Regulation).
In: eLS.
John Wiley & Sons, Ltd, 2012. Publisher's abstract
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