All the neurons and glia of the mature central nervous system (CNS) are generated from the neuroepithelial stem cells (NSCs) of the embryonic neural tube.  How do the NSCs decide to preserve their “stemness” or to embark on differentiation is my major research question.

Cross-talk between extracellular signals and cell-intrinsic programmes plays a central role in determining cell fate.  Ultimately, extrinsic signals converge on chromatin (DNA wrapped around histones) to remodel its structure and accessibility to the transcriptional machinery - either activating or silencing genes that influence cell lineage decisions.  Chromatin remodelling in a broad sense includes DNA methylation, post-translational histone modifications and non-coding RNAs.  Intriguingly, mutations in several of the known chromatin modifying enzymes lead to mental retardation syndromes in humans, highlighting their importance in both guiding normal neural development and maintaining neural function.

My special interest is to understand how post-translational histone modifications control cortical development.  Histones can be phosphorylated, acetylated and methylated, to name but a few modifications.  The precise combination of histone modifications constitutes the “histone code” that defines the transcriptional profile of the cell and hence its identity.  I am focusing on the role of histone/protein arginine methylation in the control of NSC “stemness”, proliferation and differentiation.