The spatio‐temporal and subcellular expression of the candidate Down syndrome gene Mnb/Dyrk1A in the developing mouse brain suggests distinct sequential roles in neuronal development
Abstract
It is widely accepted that the neurological alterations in Down syndrome (DS) are principally due to modifications in developmental processes. Accordingly, a large part of the research on DS in recent years has focused on chromosome 21 genes that influence brain development. MNB/DYRK1A is one of the genes on human chromosome 21 that has raised most interest, due to its relationship with the brain functions that are altered in DS. Although a number of interesting experimental mouse models for DS are being developed, we still know little about the expression of Mnb/Dyrk1A during mouse brain development. Here, we report that Mnb/Dyrk1A displays a rather dynamic spatio-temporal expression pattern during mouse central nervous system development. Our data indicate that Mnb/Dyrk1A is specifically expressed in four sequential developmental phases: transient expression in preneurogenic progenitors, cell cycle-regulated expression in neurogenic progenitors, transient expression in recently born neurones, and persistent expression in late differentiating neurones. Our results also suggest that the subcellular localization of MNB/DYRK1A, including its translocation to the nucleus, is finely regulated. Thus, the MNB/DYRK1A protein kinase could be a key element in the molecular machinery that couples sequential events in neuronal development. This rich repertoire of potential functions in the developing central nervous system is suitable to be linked to the neurological alterations in DS t…
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DYRK1A is expressed in non-trisomic ICR mice at several embryonic stages in cortical layers, forebrain neurons, and the nucleus of cells from the ventricular zone.
“DYRK1A is expressed in non-trisomic mice at several embryonic stages in cortical layers, forebrain neurons, and the nucleus of cells from the ventricular zone in ICR mice (Hammerle et al., 2008).”
From Sex-specific developmental alterations in DYRK1A expression in the brain of a Down syndrome mouse model (2024) · cites this paper as Hammerle et al., 2008
Transient expression of Dyrk1a could promote cell cycle exit, and its subsequent downregulation allows cells to undergo neuronal differentiation.
“Thus, the transient expression of Dyrk1a could promote cell cycle exit, and its subsequent down regulation allows cells to undergo neuronal differentiation (Hammerle et al., 2008; Hammerle et al., 2011).”
From Sex-specific developmental alterations in DYRK1A expression in the brain of a Down syndrome mouse model (2024) · cites this paper as Hammerle et al., 2008
At P5, DYRK1A is localized in the nucleus of cerebellar Purkinje cells in mice.
“At P5, DYRK1A was localized in the nucleus of cerebellar Purkinje cells (Hammerle et al., 2008)”
From Sex-specific developmental alterations in DYRK1A expression in the brain of a Down syndrome mouse model (2024) · cites this paper as Hammerle et al., 2008
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MNB/DYRK1A as a multiple regulator of neuronal development
Tejedor, F. J., & Hämmerle, B. (2011) · The FEBS Journal · doi:10.1111/j.1742-4658.2010.07954.x · Cited by 214 · see citing works
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“We used mouse whole-embryo cultures (E12), where all relevant neurodevelopmental stages are coexisting and DYRK1A is highly expressed in the telencephalon.(45) As shown in Figure 10, most of pSer10 p27 immunostaining in E12 embryonic mouse brain was overlapping with that of β-III-tubulin (TUJ1), a well-known marker of…”
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Altered Hippocampal-Prefrontal Neural Dynamics in Mouse Models of Down Syndrome
Chang, P., Bush, D., Schorge, S., Good, M., Canonica, T., Shing, N., Noy, S., Wiseman, F. K., Burgess, N., Tybulewicz, V. L. J., et al. (2020) · Cell Reports · doi:10.1016/j.celrep.2019.12.065 · Cited by 47 · see citing works
Hawley, L. E., Stringer, M., Deal, A. J., Folz, A., Goodlett, C. R., & Roper, R. J. (2024) · Neurobiology of Disease · doi:10.1016/j.nbd.2023.106359 · Cited by 10 · see citing works
“At P5, DYRK1A was localized in the nucleus of cerebellar Purkinje cells (Hammerle et al., 2008); At P14, significant DYRK1A expression was detected in the external granular, molecular layer, and internal granule cell layer of the cerebral cortex (Marti et al., 2003).”
- Authors
- Hämmerle, B., Elizalde, C., & Tejedor, F. J.
- Affiliations
- Instituto de Neurociencias (ES)
- Venue
- European Journal of Neuroscience
- Publisher
- Wiley
- Published
- 2008-03
- Volume
- 27
- Issue
- 5
- Pages
- 1061-1074
- ISSN
- 0953-816X (ISSN-L)
- 1460-9568
- OpenAlex
- W2104100182
- Cited by
- 82
- References
- 4
- Citations by year
- 2026: 2 · 2025: 5 · 2023: 6 · 2022: 6 · 2021: 5 · 2020: 4 · 2019: 4 · 2018: 7 · 2017: 5 · 2016: 4 · 2015: 4 · 2014: 2 · 2013: 4 · 2012: 6
- FWCI
- 5.96
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- European Journal of Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion)
- Funders
- Ministry of Education, Science and Technology
- Ministerio de Ciencia y Tecnología
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Down syndrome and intellectual disability research
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Keywords
- Down syndrome, chromosome 21 genes, mouse brain development, spatiotemporal gene expression, subcellular localization, nuclear translocation, neuronal development, protein kinases, mouse models of Down syndrome
- MeSH terms
- Dyrk Kinases, Age Factors, Animals, Animals, Newborn, Brain, Cell Differentiation, Cell Nucleus, Down Syndrome, Mice, Inbred ICR, Neurons, Protein-Tyrosine Kinases, Subcellular Fractions, Protein Serine-Threonine Kinases, Gene Expression Regulation, Developmental, Mice
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