UCLA

The subventricular zone is a well-known adult neurogenic niche that produces new neurons for the olfactory bulb and is regulated by the Reelin (Reln)-signaling pathway. Secreted Reln binds to its lipoprotein receptors and induces tyrosine phosphorylation of the intracellular adaptor protein Disabled-1 (Dab1), activating downstream signaling in neurons. If either Reln or Dab1 are missing, the signaling pathway is disrupted. It is currently unclear if the Reln-signaling pathway plays a role in the peripheral neurogenic region, namely the olfactory epithelium (OE). The OE is the site where olfactory sensory neurons (OSNs) are continuously generated throughout life and where the OSNs detect odorants. To investigate the role of the Reln-signaling pathway on the neurogenic ability of the OE, we generated a tissue-specific, conditional Dab1 mice line (Olfactory Marker Protein (OMP)-cre; Dab1-flox) which deletes Dab1 only in OMP-expressing mature OSNs. We first asked if there were differences in stem cell proliferation across the genotypes by immunostaining for Ki67 and Sox2. We found the conditional Dab1 mutants (OMP-cre; Dab1 f/f) had significantly fewer Ki67-positive proliferating cells and Sox2-positive olfactory stem cells than the no-cre controls. We then examined differences in NeuroD1 expression and found fewer NeuroD1-labeled immediate neuronal precursors in the OMP-cre; Dab1 f/f mutants compared with no-cre controls. Next, we analyzed mature OSNs that express OMP but found no differences between the no-cre controls and OMP-cre; Dab1 f/f mutants. We also analyzed apoptotic cell death using Casp3 antibodies but detected no differences between the no-cre control and OMP-cre; Dab1 f/f mutants. These results reveal that loss of the Dab1 gene leads to reduced adult neurogenesis in the OSN progenitor cells, but there were no changes in the average number of OMP-labeled mature OSNs.