Abstract
New neurons are added on a daily basis to the olfactory bulb (OB) of a mammal, and this phenomenon exists throughout its lifetime. These new cells are born in the subventricular zone and migrate to the OB via the rostral migratory stream (RMS). To examine the role of the prokineticin receptor 2 (Prokr2) in neurogenesis, we created a Prokr2 null mouse, and report a decrease in the volume of its OB and also a decrease in the number of bromodeoxyuridine (BrdU)-positive cells. There is disrupted architecture of the OB, with the glomerular layer containing terminal dUTP nick-end labeling (TUNEL) -positive nuclei and also a decrease in tyrosine hydroxylase-positive neurons in this layer. In addition, there are increased numbers of doublecortin-positive neuroblasts in the RMS and increased PSA-NCAM (polysialylated form of the neural cell adhesion molecule) -positive neuronal progenitors around the olfactory ventricle, indicating their detachment from homotypic chains is compromised. Finally, in support of this, Prokr2-deficient cells expanded in vitro as neurospheres are incapable of migrating towards a source of recombinant human prokineticin 2 (PROK2). Together, these findings suggest an important role for Prokr2 in OB neurogenesis.
Highlights
It is well established that there are two main areas where neurogenesis occurs in the adult mammalian brain, the dentate gyrus of the hippocampus and the olfactory bulb (OB; for reviews, see Gould et al, 1999; Alvarez-Buylla & Garcia-Verdugo, 2002; Watts et al, 2005)
Anatomical analysis of the brain demonstrated that the sizes of the right and left OB were symmetrically reduced in m ⁄ m mice (n 1⁄4 7) when compared with their + ⁄ + littermate controls (n 1⁄4 6; Fig. 1A–D) and + ⁄ m controls (n 1⁄4 7; data not shown)
The normal morphology of the OB was distorted, in that there was a distinct absence of the glomerular layer (GL), mitral cell layer and internal plexiform layer in m ⁄ m mice (Fig. 1E and F)
Summary
It is well established that there are two main areas where neurogenesis occurs in the adult mammalian brain, the dentate gyrus of the hippocampus and the olfactory bulb (OB; for reviews, see Gould et al, 1999; Alvarez-Buylla & Garcia-Verdugo, 2002; Watts et al, 2005). The prokineticins (Prok and Prok2) are two recently identified secreted bioactive molecules (Li et al, 2001; LeCouter et al, 2003). Signal transduction of both molecules is via two closely related Gprotein-coupled receptors (Prokr and Prokr2; Lin et al, 2002; Masuda et al, 2002; Soga et al, 2002). Of particular relevance to this study, Prokr and Prokr expression has been detected by in situ hybridization in the SVZ, RMS, olfactory ventricle ependyma and subependymal layers, while Prok, but not Prok, is expressed in the
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