Chromatin remodelling and cell fate plasticity during neuronal maturation

Once a neuron has been generated by a mitotic progenitor, it is post-mitotic and will not divide again. Whilst cellular changes during neuronal maturation are well studied, relatively little is known about how the epigenetic state of the genome changes and how these changes relate to the loss of cell fate plasticity during neuronal maturation.

We have identified candidate factors that could be facilitating the ‘locking down’ of neural stem cell genes (NuRD complex (MEP-1) and the condensin complex (Cap-G)).

Knockdown of Cap-G and MEP-1 specifically in neurons (from their birth onwards) results in developmental arrest and dramatic gene expression changes, including aberrant expression of genes that are not normally expressed in the developing brain. Also, both factors show dynamic binding to chromatin during the process of neuronal maturation.

We aim to build on these findings to develop a mechanistic understanding of how the neuronal genome is remodelled to restrict developmental plasticity.