Studies of the hindbrain roof plate organiser in the chick embryo

Abstract

Organisers are specialised groups of cells that non-autonomously pattern adjacent cell populations. The dorsal midline, or roof plate, of the developing CNS is one such organiser and is required for the specification of specific subtypes of dorsal neurons. Organisers often comprise boundaries between molecularly distinguishable compartments, however the roof plate does not fit with this model; for the most part it constitutes a narrow strip of cells that separate two molecularly indistinguishable compartments (the two halves of the neural tube), but at certain anteroposterior locations, such as the hindbrain, it is expanded to form a thin epithelium that tents over a ventricle. Using chick embryos, I have investigated a hypothesis that reconciles the roof plate with this emergent model, in which the organiser properties of the roof plate are invested in its boundaries. Using in vitro co-culture, I show that the gdf7- positive roof plate boundary and its signalling properties can be regenerated in roof platederived tissue at the interface between hindbrain roof plate epithelium and neuroepithelium. Further, this gdf7-positive boundary is required for the expression of cath1, which marks the dorsal-most pool of neural progenitors in the hindbrain. Many organisers require Notch signalling and downstream Hairy/ Enhancer of split (Hes) transcription factors for their formation or maintenance. Using electroporation of the hindbrain roof plate epithelium – neuroepithelium boundary, I find that Delta-Notch signalling is sufficient to convert cells from a roof plate epithelial to a roof plate boundary fate. Further, correct levels of expression of chairy2 (a hes1 homologue) are required for the maintenance of the roof plate boundary. Finally, I show that the roof plate boundary is a bidirectional signalling centre that not only patterns adjacent neuroepithelium, but is also required for the differentiation of choroid plexus epithelium from roof plate epithelium.

Date of Award	1 Mar 2012
Original language	English
Awarding Institution	King's College London
Supervisor	Richard Wingate (Supervisor) & Jon Clarke (Supervisor)