Loss of Function of the Neural Cell Adhesion Molecule NrCAM Regulates Differentiation, Proliferation and Neurogenesis in Early Postnatal Hypothalamic Tanycytes.
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Authors
Moore, Alex
Chinnaiya, Kavitha
Kim, Dong Won
Brown, Sarah
Stewart, Iain
Robins, Sarah
Dowsett, Georgina K C
Muir, Charlotte
Travaglio, Marco
Lewis, Jo E
Ebling, Fran
Blackshaw, Seth
Placzek, Marysia
Publication Date
2022-04-07Journal Title
Frontiers in neuroscience
ISSN
1662-4548
Volume
16
Language
eng
Type
Article
This Version
VoR
Metadata
Show full item recordCitation
Moore, A., Chinnaiya, K., Kim, D. W., Brown, S., Stewart, I., Robins, S., Dowsett, G. K. C., et al. (2022). Loss of Function of the Neural Cell Adhesion Molecule NrCAM Regulates Differentiation, Proliferation and Neurogenesis in Early Postnatal Hypothalamic Tanycytes.. Frontiers in neuroscience, 16 https://doi.org/10.3389/fnins.2022.832961
Abstract
Hypothalamic tanycytes are neural stem and progenitor cells, but little is known of how they are regulated. Here we provide evidence that the cell adhesion molecule, NrCAM, regulates tanycytes in the adult niche. NrCAM is strongly expressed in adult mouse tanycytes. Immunohistochemical and <i>in situ</i> hybridization analysis revealed that NrCAM loss of function leads to both a reduced number of tanycytes and reduced expression of tanycyte-specific cell markers, along with a small reduction in tyrosine hydroxylase-positive arcuate neurons. Similar analyses of NrCAM mutants at E16 identify few changes in gene expression or cell composition, indicating that NrCAM regulates tanycytes, rather than early embryonic hypothalamic development. Neurosphere and organotypic assays support the idea that NrCAM governs cellular homeostasis. Single-cell RNA sequencing (scRNA-Seq) shows that tanycyte-specific genes, including a number that are implicated in thyroid hormone metabolism, show reduced expression in the mutant mouse. However, the mild tanycyte depletion and loss of markers observed in NrCAM-deficient mice were associated with only a subtle metabolic phenotype.
Keywords
Hypothalamus, Neurogenesis, Neural cell adhesion molecules, Astrocytes, tanycyte, Radial Glia, Nrcam, Scrna Seq
Sponsorship
Wellcome Trust (212247/Z/18/Z)
Identifiers
35464310, PMC9022636
External DOI: https://doi.org/10.3389/fnins.2022.832961
This record's URL: https://www.repository.cam.ac.uk/handle/1810/337496
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