Multiplex genetic fate mapping reveals a novel route of neocortical neurogenesis, which is altered in the Ts65Dn mouse model of down syndrome.
Open accessAbstract
While several major classes of neocortical neural precursor cells have been identified, the lineal relationships and molecular profiles of these cells are still largely unknown. Furthermore, the individual contribution of each cell class to neocortical growth during normal development and in neurodevelopmental disorders has not been determined. Using a novel fate-mapping approach, we demonstrate that precursors in the embryonic ventricular (VZ) and subventricular zones (SVZ), which give rise to excitatory neurons, are divided into distinct subtypes based on lineage profile, morphology, and transcription factor expression in vivo. Using this technique, we show that short neural precursors are a unique class of VZ intermediate progenitors derived from radial glial cells and are distinct from the multipolar Tbr2(+)intermediate progenitors, which divide in the SVZ. To test whether these multiple groups of intermediate progenitors are redundant or whether they are necessary for proper neocortical growth, we measured precursor cell diversity in the Ts65Dn mouse model of Down syndrome (DS), which exhibits reduced neurogenesis and postnatal microcephaly. We report that SNP generation is markedly reduced in the Ts65Dn VZ during mid-neurogenesis, indicating that faulty specification of this progenitor pool is a central component of the neocortical abnormality in DS. Together, these findings demonstrate that neocortical neurons are produced via multiple indirect routes during embryonic development and that these parallel streams of neurogenesis collectively contribute to the proper growth and development of the neocortex.
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In Ts65Dn, NPC subtype may be shifted during development.
“Reports in the Ts65Dn mouse model indicate that NPC subtype may be shifted during development (Tyler and Haydar, 2013).”
From Neurodevelopment in Down syndrome: Concordance in humans and models (2022) · cites this paper as Tyler and Haydar, 2013
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“Reports in the Ts65Dn mouse model indicate that NPC subtype may be shifted during development (Tyler and Haydar, 2013).”
BackgroundSelf-citation
- Authors
- Tyler, W. A., & Haydar, T. F.
- Affiliations
- Boston University (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2013-03-20
- Volume
- 33
- Issue
- 12
- Pages
- 5106-5119
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC3785112
- OpenAlex
- W2081315576
- Cited by
- 81
- References
- 6
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 4 · 2023: 4 · 2022: 6 · 2021: 8 · 2020: 8 · 2019: 6 · 2018: 2 · 2017: 8 · 2016: 9 · 2015: 10 · 2014: 9 · 2013: 5
- FWCI
- 4.08
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (R01NS051852, NS076503, R01NS076503, NS051852)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD057580, R01HD057580)
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Congenital heart defects research
- Keywords
- neocortical neurogenesis, Ts65Dn mouse model, Down syndrome, intermediate progenitor cells, radial glia, subventricular zone, ventricular zone, Tbr2, transcription factor expression, microcephaly, excitatory neurons, neurodevelopmental disorders
- MeSH terms
- Fatty Acid-Binding Protein 7, Animals, Cell Division, Disease Models, Animal, Down Syndrome, Female, Male, Membrane Glycoproteins, Mice, Inbred C3H, Mice, Inbred C57BL, Mice, Mutant Strains, Microcephaly, Nerve Tissue Proteins, Organ Culture Techniques, Pregnancy, Receptors, Antigen, T-Cell, alpha-beta, Genes, Reporter, Gene Expression Regulation, Developmental, Microscopy, Video, Cell Lineage, Integrases, Neocortex, Excitatory Amino Acid Transporter 1, Fatty Acid-Binding Proteins, Mice, Neurogenesis, Neural Stem Cells
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