The first indication that PS1 may play a role in neurogenesis has been provided by experiments in mice with genomic deletions of PSEN1 exhibiting severely abnormal somitogenic and neurogenic processes in the brain (Wong et al., 1997; Shen et al., 1997). The ventricular zone is substantially thinner in the brain of these mice after embryonic day 14.5, indicating a drastic reduction in the number of neural progenitor cells (Shen et al., 1997). In addition, expression of notch-1 and its ligand is dramatically reduced (Wong et al., 1997). The lethality of this mutation has hampered further studies of the role of PS1 in a natural brain setting in postnatal life. That led to the examination of neurogenesis in FAD-linked PS1 transgenic mice. Nevertheless, given the numerous cellular activities in which PS1 is implicated, most currently available transgenic mice offer little advantage when it comes to processes that take place postnatally in restricted brain areas with a unique population of dividing progenitor cells, as transgenes are expressed in a ubiquitously, nonspecific manner. Lack or dysfunction of PS1 in mature neurons in the brain may induce processes that may alter neurogenesis indirectly (Chen et al., 2008).
