Our current laboratory research
The adult vertebrate brain is a highly complex organ, containing billions of neurones connected by axons in a precise pattern. The basic organisation of the brain is determined during early embryonic development when the first neurones establish a simple scaffold of axon tracts. Projects in our lab are aimed at understanding the molecular programmes that underlie the development of the early neurones and their interaction with the surrounding tissues.
Early axon scaffold
Our comparative study of the early axon scaffold, funded by the Anatomical Society, revealed that the ventral longitudinal tract made up of TPOC and MLF, and the transversal TPC are strictly conserved in all vertebrates (Ware & Schubert, in preparation).
The detailed anatomical analysis of our primary model, the chick embryo, showed that the MLF is formed by three distinct groups of neurones in the caudal diencephalon, located in the same position as the neurones for the TPC (Fig. 1; Ware & Schubert, 2011). Studying fate determination and axon guidance during the formation of MLF and TPC has become a major focus of the lab.
Gene regulatory network
Transcription factors have long been recognised as key factors in cell fate determination, intricately linked with patterning signals. Some time ago we found that homeobox genes like Sax1 and Pax6 are expressed in discrete domains during early brain development (Schubert et al., 1995). By BBSRC-funded gain-of-function studies we have shown that ectopic expression of Sax1 affects the formation of the MLF, and that Sax1 along with genes like Emx2 or Six3may form a transcriptional code for the patterning of ventral mesencephalon and diencephalon (Fig. 2; Schubert & Lumsden, 2005; Ahsan et al., 2007). Current work in the lab, supported by initial funding from the AdMiN Interreg project, is targeted at analysing the transcriptional network by deciphering how the expression of Sax1 and Emx2 is regulated (Holly Keats).
Axon guidance mechanisms
Establishing the early axon scaffold requires not only the precise control of neuronal differentiation, but also tight regulation of axon outgrowth. Funded by the Royal Society, we have characterised the expression of the major axon guidance molecules and their receptors at early stages (Riley et al. 2010). A number of candidate molecules likely to be involved in MLF and TPC guidance emerged from the study, and their function is currently being investigated.
Early neuro-vascular interaction
A more recent focus in the lab is the cross-talk between neural and mesodermal cells during the vascularisation of the brain. This project is part of the EU-funded TC2N network and brings together the expertise of Colin Sharpe, Matt Guille and our lab in Portsmouth with our partners David Vaudry and Hélène Castel in Rouen (Suzannah Page and Martin Devonshire).