Molecular control of neural patterning
Our lab works almost exclusively on CNS regionalization, with a particular focus on the nature and significance of developmental compartments. The formation of cell-tight compartments and their maintenance by lineage restriction boundaries has long been recognised as a key feature of insect development, where the more important functions of the boundaries include maintaining the position of local signalling centres and the prevention of cell mingling, which might disrupt emergent spatial organization in an otherwise homogeneous tissue.
Our earlier work revealed the existence of compartments also in the vertebrates, specifically in the hindbrain region of the CNS (Lumsden and Keynes, 1989; Fraser et al., 1990), where the cell segregation mechanisms involved in their formation and maintenance are still being elucidated - the Eph receptors and ephrin ligands that are expressed selectively in odd- and even-numbered rhombomeres are thought to be responsible for effecting cell lineage restriction, but we know very few candidate regulatory genes that would be required upstream of these realizators.
To illuminate this process, we are using Affymetrix gene chip technology to profile the transcriptomes of individual rhombomeres at the stage of initial segmentation. Interesting transcripts identified thus far include those of a number of transcription factors that have alternate expression, in either the odd rhombomeres or the evens. Functional studies on some of these genes are in progress.