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.


BM&L-December 2005