Olfactory bulb hypoplasia in Prokr2 null mice stems from defective neuronal progenitor migration and differentiation
Open accessAbstract
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.
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When PK2 binds to PK-R2, signaling cascades important for development of the olfactory system and GnRH neuronal progenitors are initiated.
“When PK2 binds to PK-R2, signaling cascades that are important for development of the olfactory system and GnRH neuronal progenitors are initiated.”
From The genetic and molecular basis of idiopathic hypogonadotropic hypogonadism (2009) · cites this paper as [24]
GnRH neurons in Prok2−/− mice cross the cribriform plate to enter the central nervous system during embryonic development but do not migrate into and populate the hypothalamus.
“Interestingly, GnRH neurons in Prok2−/− mice were able to cross the cribriform plate (a horizontal plate of the ethmoid bone) to enter the central nervous system during embryonic development, but the neurons did not migrate into and populate the hypothalamus.”
From The genetic and molecular basis of idiopathic hypogonadotropic hypogonadism (2009) · cites this paper as [24]
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The genetic and molecular basis of idiopathic hypogonadotropic hypogonadism
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- Authors
- Prosser, H. M., Bradley, A., & Caldwell, M. A.
- Affiliations
- Wellcome Sanger Institute (GB)
- University of Cambridge (GB)
- Corresponding author
- Caldwell, Maeve A.
- Venue
- European Journal of Neuroscience
- Publisher
- Wiley
- Published
- 2007-12
- Volume
- 26
- Issue
- 12
- Pages
- 3339-3344
- ISSN
- 0953-816X (ISSN-L)
- 1460-9568
- PMC
- PMC2228368
- OpenAlex
- W2109918998
- Cited by
- 77
- References
- 26
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 3 · 2023: 4 · 2022: 4 · 2021: 5 · 2020: 4 · 2019: 8 · 2018: 1 · 2017: 7 · 2016: 2 · 2015: 1 · 2014: 2 · 2013: 4 · 2012: 8
- FWCI
- 1.44
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- European Journal of Neuroscience (publishedVersion)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Apollo (University of Cambridge) (submittedVersion, cc-by)
- Apollo (cc-by)
- Funders
- Wellcome Trust
- Royal Society
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Sensory Systems › Olfactory and Sensory Function Studies
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Keywords
- olfactory bulb hypoplasia, PROKR2, prokineticin 2, rostral migratory stream, adult neurogenesis, subventricular zone, glomerular layer, neuroblast differentiation, doublecortin, PSA-NCAM, neurospheres
- MeSH terms
- Doublecortin Domain Proteins, Animals, Animals, Newborn, Bromodeoxyuridine, Cell Count, Cell Differentiation, Cell Movement, Female, Gastrointestinal Hormones, Homozygote, Humans, Lactation, Mice, Inbred C57BL, Microtubule-Associated Proteins, Neurons, Neuropeptides, Olfactory Bulb, Recombinant Proteins, Sialic Acids, Stem Cells, Tyrosine 3-Monooxygenase, Receptors, Peptide, Mice, Knockout, Spheroids, Cellular, Neural Cell Adhesion Molecule L1, Receptors, G-Protein-Coupled, Mice
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