Frontiers in Neuroscience (Apr 2022)
Loss of Function of the Neural Cell Adhesion Molecule NrCAM Regulates Differentiation, Proliferation and Neurogenesis in Early Postnatal Hypothalamic Tanycytes
- Alex Moore,
- Alex Moore,
- Alex Moore,
- Kavitha Chinnaiya,
- Kavitha Chinnaiya,
- Kavitha Chinnaiya,
- Dong Won Kim,
- Sarah Brown,
- Sarah Brown,
- Sarah Brown,
- Iain Stewart,
- Iain Stewart,
- Iain Stewart,
- Sarah Robins,
- Sarah Robins,
- Sarah Robins,
- Georgina K. C. Dowsett,
- Georgina K. C. Dowsett,
- Charlotte Muir,
- Marco Travaglio,
- Jo E. Lewis,
- Jo E. Lewis,
- Fran Ebling,
- Seth Blackshaw,
- Seth Blackshaw,
- Seth Blackshaw,
- Seth Blackshaw,
- Seth Blackshaw,
- Andrew Furley,
- Andrew Furley,
- Andrew Furley,
- Marysia Placzek,
- Marysia Placzek,
- Marysia Placzek
Affiliations
- Alex Moore
- School of Biosciences, The University of Sheffield, Sheffield, United Kingdom
- Alex Moore
- Bateson Centre, The University of Sheffield, Sheffield, United Kingdom
- Alex Moore
- Neuroscience Institute, The University of Sheffield, Sheffield, United Kingdom
- Kavitha Chinnaiya
- School of Biosciences, The University of Sheffield, Sheffield, United Kingdom
- Kavitha Chinnaiya
- Bateson Centre, The University of Sheffield, Sheffield, United Kingdom
- Kavitha Chinnaiya
- Neuroscience Institute, The University of Sheffield, Sheffield, United Kingdom
- Dong Won Kim
- Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, United States
- Sarah Brown
- School of Biosciences, The University of Sheffield, Sheffield, United Kingdom
- Sarah Brown
- Bateson Centre, The University of Sheffield, Sheffield, United Kingdom
- Sarah Brown
- Neuroscience Institute, The University of Sheffield, Sheffield, United Kingdom
- Iain Stewart
- School of Biosciences, The University of Sheffield, Sheffield, United Kingdom
- Iain Stewart
- Bateson Centre, The University of Sheffield, Sheffield, United Kingdom
- Iain Stewart
- Neuroscience Institute, The University of Sheffield, Sheffield, United Kingdom
- Sarah Robins
- School of Biosciences, The University of Sheffield, Sheffield, United Kingdom
- Sarah Robins
- Bateson Centre, The University of Sheffield, Sheffield, United Kingdom
- Sarah Robins
- Neuroscience Institute, The University of Sheffield, Sheffield, United Kingdom
- Georgina K. C. Dowsett
- Wellcome Trust-Medical Research Council Institute of Metabolic Science-Metabolic Research Laboratories, University of Cambridge, Cambridge, United Kingdom
- Georgina K. C. Dowsett
- School of Life Sciences, University of Nottingham, Nottingham, United Kingdom
- Charlotte Muir
- School of Life Sciences, University of Nottingham, Nottingham, United Kingdom
- Marco Travaglio
- School of Life Sciences, University of Nottingham, Nottingham, United Kingdom
- Jo E. Lewis
- Wellcome Trust-Medical Research Council Institute of Metabolic Science-Metabolic Research Laboratories, University of Cambridge, Cambridge, United Kingdom
- Jo E. Lewis
- School of Life Sciences, University of Nottingham, Nottingham, United Kingdom
- Fran Ebling
- School of Life Sciences, University of Nottingham, Nottingham, United Kingdom
- Seth Blackshaw
- Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, United States
- Seth Blackshaw
- Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD, United States
- Seth Blackshaw
- Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, United States
- Seth Blackshaw
- Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, United States
- Seth Blackshaw
- 0Kavli Neuroscience Discovery Institute, Johns Hopkins University School of Medicine, Baltimore, MD, United States
- Andrew Furley
- School of Biosciences, The University of Sheffield, Sheffield, United Kingdom
- Andrew Furley
- Bateson Centre, The University of Sheffield, Sheffield, United Kingdom
- Andrew Furley
- Neuroscience Institute, The University of Sheffield, Sheffield, United Kingdom
- Marysia Placzek
- School of Biosciences, The University of Sheffield, Sheffield, United Kingdom
- Marysia Placzek
- Bateson Centre, The University of Sheffield, Sheffield, United Kingdom
- Marysia Placzek
- Neuroscience Institute, The University of Sheffield, Sheffield, United Kingdom
- DOI
- https://doi.org/10.3389/fnins.2022.832961
- Journal volume & issue
-
Vol. 16
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 in situ 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
