Development of vertebrate head...

My group has worked extensively on development of vertebrate head. This is a complex process involving interactions between disparate embryonic cells types.

A significant feature of head development is that the strategies employed here differ from those used in the rest of the body, particularly with respect to the deployment of three key embryonic tissue: the neural crest, the neurogenic placodes and the pharyngeal endoderm. We have therefore devoted much of our energies to the analysis of these populations and the cross talk between them.

This area of research has implications for our understanding of the aetiology of numerous birth defects. Indeed, the fact that the development of the head is complex is borne out by the high number of craniofacial defects in live births. Our work also informs us of the how the vertebrates evolved. The real difference between the vertebrates and our nearest relatives lie in the organisation of the head, and these difference are thought to have their basis in alterations to the programme that underlies the development of the head. Consequently, our work also feeds into our understanding of the evolutionary origin of the vertebrates.

Cranial neural crest

Recently, we have been focussing on how fates are allocated to the neural crest cells. We have shown that cells follow an ectomesenchymal fate as a result of epithelial cues, primarily from the pharyngeal endoderm, and that this involves FGF signalling (Blentic et al, 2008).

We are now moving on to identify which other molecules are required to direct neural crest cells towards particular ectomesenchymal fates – cartilage versus bone, for example. We have also begun to identify the cues that direct cranial neural crest cells to follow a neuronal fate, in particular how sensory neurons are generated (Thompson et al 2010).

Neurogenic placodes

We have also been focussing on the cellular mechanisms underlying the emigration of neuronal cells from the neurogenic placodes. We have demonstrated that the cells migrating from the placodes are neuroblasts; they divide as they migrate and, more recently (Graham et al. 2007), we have been analysing their potential. From this work, it is becoming increasingly clear that the neurogenic placodes function as a stem cell niche, and that the neuroblasts migrating away from the placodes are transit amplifying cells (Blentic et al. 2011).

We will identify the routes through which the stem cell niche/placode is maintained over the period of neuroblast production and when and by what mechanism the stem cell niche/placode ceases to exist. As the neuroblasts leave the placodes over a protracted period, we will also determine if there is a relationship between the time of emigration from the placode and the organisation of the corresponding sensory ganglia. We also want to analyse the behaviour of the transit amplifying cells and to determine how many rounds of division they go through.

Pharyngeal segmentation

Finally, we will pursue our studies of the pharyngeal endoderm and its derivatives. We have shown that pharyngeal segmentation is driven by the pharyngeal endoderm and that the more posterior pharyngeal arches are formed in a different manner from the anterior (Graham, 2008).

This difference is reflected in a number of situations, including DiGeorge syndromes, in which the development of the posterior arches is affected but not the anterior. We wish to further scrutinise the roles of retinoid and FGF signalling in coordinating the development of the posterior arches. We are interested in determining the mechanism through which the posterior arches become internalised and why failures in this process can lead to branchial fistulae in some individuals.