Development of the superior temporal neocortex is anomalous in trisomy 21
Abstract
Trisomy 21 (Down syndrome) is the most common inherited form of mental retardation in the United States, however, the basis of impaired cognition is unknown. We have used recently developed stereological cell counting techniques to quantitatively examine the pattern of neuronal migration and maturation in one neocortical area during gestation in normal development and in trisomy 21. Normal development of the cerebral cortex occurs in two general sequences: Beginning at approximately 7-8 weeks gestation, migration of cells destined to become neurons results in the accumulation of cells in the cortical mantle. This process is largely complete by 20-21 weeks. Over the next 7-10 weeks an "inside-out" differentiation into lamina of different neuronal densities occurs. Our data suggest that the second phase of cortical development, the emergence of lamination, is both delayed and disorganized in trisomy 21. The observed pattern of cortical maturation may reflect an abnormality in axonal and dendritic arborization that subsequently subserve the connectional and functional units underlying normal cognition.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Trisomy 21 causes complex spatiotemporal disturbances in neural development.
“Morphometric and cellular studies on human brain indicate that trisomy 21 causes complex spatiotemporal disturbances in neural development (Golden and Hyman, 1994; Larsen et al., 2008; Reeves and Haydar, 2011).”
From Down Syndrome Developmental Brain Transcriptome Reveals Defective Oligodendrocyte Differentiation and Myelination (2016) · cites this paper as Golden and Hyman, 1994
The fetal cortex, cerebellum and hippocampus have all been shown to contain fewer neurons in individuals with Down syndrome than in controls, albeit based on small sample sizes.
“The fetal cortex, cerebellum and hippocampus have all been shown to contain fewer neurons in individuals with DS than in controls40–48, albeit based on small sample sizes17.”
From Consequences of trisomy 21 for brain development in Down syndrome (2024) · cites this paper as [41]
Evidence for specific deficits in late-born upper-layer neurons in Down syndrome from observations of post-mortem tissue suggests that specific temporally defined progenitors are affected.
“Evidence for specific deficits in late-born upper-layer neurons in DS from observations of post-mortem tissue further suggests that specific temporally defined progenitors are affected41,84.”
From Consequences of trisomy 21 for brain development in Down syndrome (2024) · cites this paper as [41]
Other studies have not identified any change in cellular density in the superior temporal neocortex prior to 23 weeks gestation and instead report Down syndrome related hypocellularity only appearing later in development.
“However, other studies have not identified any change in cellular density in the superior temporal neocortex prior to 23 weeks gestation and instead report DS related hypocellularity only appearing later in development (Schmidt-Sidor et al., 1990; Golden and Hyman, 1994).”
From Neurodevelopment in Down syndrome: Concordance in humans and models (2022) · cites this paper as Golden and Hyman, 1994
Volumetric changes in Down syndrome are apparent as early as 23 weeks gestation in developing fetuses.
“Indeed, as early as 23 weeks gestation, volumetric changes are apparent in developing fetuses with DS (Golden and Hyman, 1994)”
From Neurodevelopment in Down syndrome: Concordance in humans and models (2022) · cites this paper as Golden and Hyman, 1994
The cerebral cortical hemispheres, cerebellum, and hippocampal formations are significantly reduced in size in people with Down syndrome.
“In particular, the cerebral cortical hemispheres, cerebellum, and hippocampal formations are significantly reduced in size (Wisniewski, 1990; Golden and Hyman, 1994; Kesslak et al., 1994; Raz et al., 1995; Pinter et al., 2001; Tarui et al., 2020; McCann et al., 2021).”
From Neurodevelopment in Down syndrome: Concordance in humans and models (2022) · cites this paper as Golden and Hyman, 1994
Cited by
Sorted by citations
Neuroanatomy of Down’s Syndrome: A High-Resolution MRI Study
Pinter, J. D., Eliez, S., Schmitt, J. E., Capone, G. T., & Reiss, A. L. (2001) · American Journal of Psychiatry · doi:10.1176/appi.ajp.158.10.1659 · Cited by 452 · see citing works
Olmos-Serrano, J. L., Kang, H. J., Tyler, W. A., Silbereis, J. C., Cheng, F., Zhu, Y., Pletikos, M., Jankovic-Rapan, L., Cramer, N. P., Galdzicki, Z., et al. (2016) · Neuron · doi:10.1016/j.neuron.2016.01.042 · Cited by 239 · see citing works
“Morphometric and cellular studies on human brain indicate that trisomy 21 causes complex spatiotemporal disturbances in neural develop- ment (Golden and Hyman, 1994; Larsen et al., 2008; Haydar and Reeves, 2012).”
Self-citationChakrabarti, L., Galdzicki, Z., & Haydar, T. F. (2007) · The Journal of Neuroscience · doi:10.1523/jneurosci.3406-07.2007 · Cited by 199 · see citing works
Long, K. R., Newland, B., Florio, M., Kalebic, N., Langen, B., Kolterer, A., Wimberger, P., & Huttner, W. B. (2018) · Neuron · doi:10.1016/j.neuron.2018.07.013 · Cited by 196 · see citing works
Duchon, A., & Herault, Y. (2016) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2016.00104 · Cited by 181 · see citing works
Truncation of the Down syndrome candidate gene DYRK1A in two unrelated patients with microcephaly
Møller, R. S., Kübart, S., Hoeltzenbein, M., Heye, B., Vogel, I., Hansen, C. P., Menzel, C., Ullmann, R., Tommerup, N., Ropers, H.-H., et al. (2008) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2008.03.001 · Cited by 163 · see citing works
Tang, X.-Y., Xu, L., Wang, J., Hong, Y., Wang, Y., Zhu, Q., Wang, D., Zhang, X.-Y., Liu, C.-Y., Fang, K.-H., et al. (2021) · Journal of Clinical Investigation · doi:10.1172/jci135763 · Cited by 143 · see citing works
Communication breaks-Down: From neurodevelopment defects to cognitive disabilities in Down syndrome
Contestabile, A., Benfenati, F., & Gasparini, L. (2010) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2010.01.003 · Cited by 134 · see citing works
Huo, H.-Q., Qu, Z.-Y., Yuan, F., Ma, L., Yao, L., Xu, M., Hu, Y., Ji, J., Bhattacharyya, A., Zhang, S.-C., et al. (2018) · Stem Cell Reports · doi:10.1016/j.stemcr.2018.02.001 · Cited by 122 · see citing works
Mukaetova‐Ladinska, E. B., Arnold, H., Jaros, E., Perry, R., & Perry, E. (2004) · Neuropathology and Applied Neurobiology · doi:10.1111/j.1365-2990.2004.00574.x · Cited by 115 · see citing works
Aziz, N. M., Guedj, F., Pennings, J. L. A., Olmos-Serrano, J. L., Siegel, A., Haydar, T. F., & Bianchi, D. W. (2018) · Disease Models & Mechanisms · doi:10.1242/dmm.031013 · Cited by 118 · see citing works
Najas, S., Arranz, J., Lochhead, P. A., Ashford, A. L., Oxley, D., Delabar, J. M., Cook, S. J., Barallobre, M. J., & Arbonés, M. L. (2015) · EBioMedicine · doi:10.1016/j.ebiom.2015.01.010 · Cited by 92 · see citing works
Absence of Prenatal Forebrain Defects in the Dp(16)1Yey/+ Mouse Model of down Syndrome.
Goodliffe, J. W., Olmos-Serrano, J. L., Aziz, N. M., Pennings, J. L. A., Guedj, F., Bianchi, D. W., & Haydar, T. F. (2016) · The Journal of Neuroscience · doi:10.1523/jneurosci.2513-15.2016 · Cited by 65 · see citing works
Neurodevelopment in Down syndrome: Concordance in humans and models
Klein, J. A., & Haydar, T. F. (2022) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2022.941855 · Cited by 47 · see citing works
“However, other studies have not identified any change in cellular density in the superior temporal neocortex prior to 23 weeks gestation and instead report DS related hypocellularity only appearing later in development (Schmidt-Sidor et al., 1990; Golden and Hyman, 1994).”
BackgroundShaw, P. R., Klein, J. A., Aziz, N. M., & Haydar, T. F. (2020) · Disease Models & Mechanisms · doi:10.1242/dmm.046243 · Cited by 45 · see citing works
Tramutola, A., Pupo, G., Di Domenico, F., Barone, E., Arena, A., Lanzillotta, C., Broekaart, D., Blarzino, C., Head, E., Butterfield, D. A., et al. (2016) · Journal of Alzheimer s Disease · doi:10.3233/jad-151105 · Cited by 40 · see citing works
Altered patterning of trisomy 21 interneuron progenitors
Giffin-Rao, Y., Sheng, J., Strand, B., Xu, K., Huang, L., Medo, M., Risgaard, K. A., Dantinne, S., Mohan, S., Keshan, A., et al. (2022) · Stem Cell Reports · doi:10.1016/j.stemcr.2022.05.001 · Cited by 38 · see citing works
Astrocytes in Down Syndrome Across the Lifespan
Ponroy Bally, B., & Murai, K. K. (2021) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2021.702685 · Cited by 35 · see citing works
Consequences of trisomy 21 for brain development in Down syndrome
Russo, M. L., Sousa, A. M. M., & Bhattacharyya, A. (2024) · Nature Reviews Neuroscience · doi:10.1038/s41583-024-00866-2 · Cited by 28 · see citing works
“Specifically, the production and differentiation of neurons and astrocytes are disrupted during neurodevelopment in DS, resulting in fewer neurons and a greater proportion of astrocytes relative to neurons 41,46,99,101,102,160 .”
Shiohama, T., Levman, J., Baumer, N., & Takahashi, E. (2019) · Pediatric Neurology · doi:10.1016/j.pediatrneurol.2019.03.015 · Cited by 27 · see citing works
Comprehensive volumetric phenotyping of the neonatal brain in Down syndrome
Fukami-Gartner, A., Baburamani, A. A., Dimitrova, R., Patkee, P. A., Ojinaga-Alfageme, O., Bonthrone, A. F., Cromb, D., Uus, A. U., Counsell, S. J., Hajnal, J. V., et al. (2023) · Cerebral Cortex · doi:10.1093/cercor/bhad171 · Cited by 24 · see citing works
Biphasic cell cycle defect causes impaired neurogenesis in down syndrome
Sharma, V., Nehra, S., Do, L. H., Ghosh, A., Deshpande, A. J., & Singhal, N. (2022) · Frontiers in Genetics · doi:10.3389/fgene.2022.1007519 · Cited by 14 · see citing works
Ishihara, K. (2021) · Genes · doi:10.3390/genes12101598 · Cited by 8 · see citing works
- Authors
- Golden, J. A., & Hyman, B. T.
- Affiliations
- Brigham and Women's Hospital (US)
- Massachusetts General Hospital (US)
- Corresponding author
- Golden, Jeffrey A.
- Venue
- Journal of Neuropathology & Experimental Neurology
- Publisher
- Oxford University Press (OUP)
- Published
- 1994-09
- Volume
- 53
- Issue
- 5
- Pages
- 513-520
- ISSN
- 0022-3069 (ISSN-L)
- 1554-6578
- OpenAlex
- W1992933562
- Cited by
- 210
- References
- 0
- Citations by year
- 2026: 2 · 2025: 8 · 2024: 12 · 2023: 8 · 2022: 16 · 2021: 5 · 2020: 3 · 2019: 8 · 2018: 11 · 2017: 7 · 2016: 10 · 2015: 9 · 2014: 2 · 2013: 9 · 2012: 14
- FWCI
- 3.60
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neuropathology & Experimental Neurology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (AG-08487)
- 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, cortical development, neuronal migration, cortical lamination, cortical maturation, gestational development, intellectual disability
- MeSH terms
- Cell Movement, Down Syndrome, Embryonic and Fetal Development, Humans, Reference Values, Temporal Lobe
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
