NOTCH ROLE IN THE BASAL BRAIN DEVELOPMENT
Striatum is the major
recipient to the basal ganglia from the cerebral cortex, thalamus and brain
stem, and plays a central role in basal forebrain functions which include
control of movement and a role in cognition, mood and non-motor behaviour. A research
by Mason et al. (Notch signaling
coordinates the patterning of striatal compartments. Development 132, 4247-4258, 2005) provides strong evidence that Notch activity is crucial
for neurogenesis in the basal forebrain and specifically for the generation of
striatal nerve cells.
Neuronal fate is decided by
a process of signaling between adjacent cells in the proneural region.
This process depends on the interactions between two cell-surface proteins
encoded by the neurogenic genes delta and notch. Both proteins
span the cell membrane: Delta functions as a ligand and Notch
is its receptor.
Notch-1 and Notch-3 are expressed in progenitor cells in the
forebrain, and gain-of-function studies have implicated Notch-signaling
in the regulation of cell fate during forebrain development. However, because
mutants that lack Notch-1 die before the onset of neurogenesis, it has
been impossible to definitively establish the effects of Notch activity
in neurogenesis or later stages of neuronal development.
Mason and his colleagues
tackled this problem demonstrating that Notch activity in mouse
progenitor cells in the ventricular zone is crucial for regulating the
developmental timing that controls the generation of striosomes -the two
striatal compartments during development. By contrast, subsequent migration-differentition
process doesn’t need Notch activity.