脳神経科学を社会へ還流する教育研究拠点　東北大脳科学グローバルCOE

講 師 ： Alexandra Joyner
所 属 ： Memorial Sloan-Kettering Cancer Center
予定演題 ： Patterning the cerebellum in 3
ｄimensions : from lobules and molecular stripes to circuits
The most noticeable morphological feature of the cerebellum is its folded
appearance, whereby fissures separate its anteriorposterior extent into
lobules. Each lobule is molecularly coded along the mediallateral axis by
parasagittal stripes of gene expression in the Purkinje cells (PC).
Additionally, within each lobule distinct combinations of afferents
terminate and supply the cerebellum with synchronized sensory and motor
information. Strikingly, afferent terminal fields are organized into
parasagittal domains, and this pattern bears a close relationship to PC
molecular coding. Thus, cerebellum three-dimensional complexity is reflected
in a basic coordinate system that can be broken down into morphology and
molecular coding. We are studying the genetic and cellular events that
regulate formation of the coordinate system and whether the circuitry map is
dependent on patterning of the lobules and parasaggital stripes. We have
found that a key event in initiation of foliation is the acquisition of a
distinct cytoarchitecture at the base of each fissure that we term
“anchoring centers”, and that the precise timing of the appearance of
anchoring centers at the prospective base of each fissure and the subsequent
coordinated function of granule cells and Bergmann glia dictates the shape
of the folia. Our preliminary analysis of an allelic series of Engrailed1
(En1) and/or En2 homeobox mutants indicates that En1/2 regulate the
continuum of foliation patterns from the medial vermis to the hemispheres by
controlling a morphogenetic clock that determines when each of the anchoring
centers forms along the anterior-posterior axis. In addition, we find that
En1/2 regulate the pattern of the molecular code in the vermis independent
of their function in patterning foliation. Furthermore, the topography of
lumbar spinocerebellar mossy fiber terminal fields is altered in En mutants,
and the alterations correlate with changes in parasagittal molecular domains
and not
lobules.