Olfactory bulb hypoplasia in Prokr2 null mice stems from defective neuronal progenitor migration and differentiation.
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.
The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK.
Haydn M
HM
Prosser
Allan
A
Bradley
Maeve A
MA
Caldwell
D000818:Animals; D000831:Animals, Newborn; D001973:Bromodeoxyuridine; D002452:Cell Count; D002454:Cell Differentiation; D002465:Cell Movement / Q000187:drug effects; D000089622:Doublecortin Domain Proteins; D005260:Female; D005768:Gastrointestinal Hormones / Q000494:pharmacology; D006720:Homozygote; D006801:Humans; D007774:Lactation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D039842:Neural Cell Adhesion Molecule L1 / Q000378:metabolism; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D009479:Neuropeptides / Q000378:metabolism / Q000494:pharmacology; D009830:Olfactory Bulb / Q000002:abnormalities* / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D043562:Receptors, G-Protein-Coupled / Q000172:deficiency* / Q000235:genetics; D018000:Receptors, Peptide / Q000172:deficiency* / Q000235:genetics; D011994:Recombinant Proteins / Q000494:pharmacology; D012794:Sialic Acids / Q000378:metabolism; D018874:Spheroids, Cellular; D013234:Stem Cells / Q000378:metabolism / Q000473:pathology*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D000089622:Doublecortin Domain Proteins; D005768:Gastrointestinal Hormones; D008869:Microtubule-Associated Proteins; D039842:Neural Cell Adhesion Molecule L1; D009479:Neuropeptides; C423608:PROK2 protein, human; C526903:Prokr2 protein, mouse; D043562:Receptors, G-Protein-Coupled; D018000:Receptors, Peptide; D011994:Recombinant Proteins; D012794:Sialic Acids; C103469:polysialyl neural cell adhesion molecule; D014446:Tyrosine 3-Monooxygenase; D001973:Bromodeoxyuridine