Patterning and migration of the rhombic lip neuron population

The rhombic lip is the interface between two epithelia organised in different ways and with dramatically different fates: the squamous roof plate and the pseudostratified neuroepithelium. We have investigated the nature of cell-cell signalling at this transition and shown how delta-notch interactions maintain cells either side of this junction as an “organiser”. We are currently using time-lapse analysis in zebrafish to examine how structural constraints in either tissue are resolved by the differential divisions of cells either side of the rhombic lip boundary. The project is led by Dr Florent Campo-Paysaa and is a joint study with Professor Jon Clarke. This work has been previously supported by a grant from the BBSRC

Cerebellar nuclei relay information from the cerebellum to other parts of the CNS via long-range excitatory and inhibitory axons. Nuclear neurons are born at the rhombic lip as one cohort in a temporal sequence of cell production. We are examining the role of signals from the roof plate in orchestrating cell fate allocation at the rhombic lip. Do these patterning mechanisms confer a vulnerability to environmental factors in development? The team on this project comprises Margarita Pitsiani, Dr Leigh Wilson and Hong-Ting Kwok working in collaboration with Dr Alessio Delogu (Wohl Institute, KCL), Dr Cathy Fernandes (SGDP, IOPPN), Dr Albert Basson (Dental Institute) and Dr David Chambers (Wolson CARD). It has been supported by the Wellcome Trust in the past and is currently funded by King’s Health Partners.

The most remarkable temporal transition at the rhombic lip involves the transformation of migratory neurons (cerebellar and isthmic nuclei) into migratory precursors of granule cells. To understand this we have examined the role of the bHLH transcription factor NeuroD in relation to the expression of Atoh1 (Math1) within these populations. Timing of NeuroD expression is critical in regulating whether granule cells pass through a migratory precursor stage. Moreover, the presence of an external germinal layer is a relatively recent vertebrate evolutionary adaptation to land dwelling. The team involved are Michalina Hanzel and Tristan Varela and the project has been previously supported by both the BBSRC and Royal Society.