ABSTRACT Roles of FGF signalling in regional specification of midbrain and anterior hindbrain

RESUME Abstracts / Resumes 645s / Resumes 645 © 2000 NRC Canada Roles of FGF signalling in regional specification of midbrain and anterior hindbrain Ivor Mason, David Chambers, Carol Irving, Huma Shamim, and Jennifer Walshe MRC Brain Development Programme, Centre for Developmental Neurobiology, King’s College London, New Hunt’s House, Guy’s Campus, London SE1 9RT, U.K. Axial pattern is established along the vertebrate neural tube by both vertical signals from adjacent mesoderm and planar signals from organising centres. One of the best-characterised of the latter is the midbrain-hindbrain boundary, or isthmus. Tissue grafting studies have established that the isthmus is the source of signals that impart regional identity to midbrain and anterior hindbrain. Heterotopic transplants of isthmic tissue into anterior midbrain respecify it to develop posterior midbrain morphological and molecular characteristics, grafts into posterior forebrain convert that tissue to an ectopic midbrain, while grafts into posterior hindbrain cause the development of ectopic cerebellar structures. Fibroblast growth factor 8 (Fgf8) is expressed at the isthmus in all vertebrate classes. We, and others, have shown that ectopic introduction of Fgf8 in the avian embryo is sufficient to cause anterior midbrain to be converted to a posterior character and posterior forebrain to develop as midbrain. Much of this presentation will be devoted to the roles of isthmic Fgf8 in patterning anterior hindbrain; previous reports have suggested that Fgf8 does not participatein this process. Part of the fate of the most anterior hindbrain rhombomere (r), r1, is to give rise to the cerebellum. Data will be presented to show that Fgf8 functions to establish and pattern the r1 territory, thereby setting aside tissue to form the cerebellar anlage. A differential display PCR analysis to identify r1-specific genes has identified a member of a family of intracellular antagonists of Fgf signalling, sprouty2. sprouty2 is rapidly inducible by Fgf8 and its expression domain suggests that it functions as a long range antagonist of the Fgf8 signal within the anterior hindbrain. Finally, the results of studies on regeneration of isthmic tissue will be presented which provide evidence that Fgf8 and the isthmic organiser are induced and (or) maintained by a specific interaction between midbrain and r1 involving a diffusible signal.