QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (31) Citing Articles via Google Scholar Google Scholar Articles by Haydar, T. F. Articles by Krueger, B. K. Search for Related Content PubMed PubMed Citation Articles by Haydar, T. F. Articles by Krueger, B. K.

 Previous Article  |  Next Article 

Role of Founder Cell Deficit and Delayed Neuronogenesis in Microencephaly of the Trisomy 16 Mouse

Tarik F. Haydar¹, Richard S. Nowakowski³, Paul J. Yarowsky², and Bruce K. Krueger¹

Departments of ¹ Physiology and ² Pharmacology and Experimental Therapeutics, University of Maryland School of Medicine, Baltimore, Maryland 21201, and ³ Department of Neuroscience and Cell Biology, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, Piscataway, New Jersey 08854

Development of the neocortex of the trisomy 16 (Ts16) mouse, an animal model of Down syndrome (DS), is characterized by a transient delay in the radial expansion of the cortical wall and a persistent reduction in cortical volume. Here we show that at each cell cycle during neuronogenesis, a smaller proportion of Ts16 progenitors exit the cell cycle than do control, euploid progenitors. In addition, the cell cycle duration was found to be longer in Ts16 than in euploid progenitors, the Ts16 growth fraction was reduced, and an increase in apoptosis was observed in both proliferative and postmitotic zones of the developing Ts16 neocortical wall. Incorporation of these changes into a model of neuronogenesis indicates that they are sufficient to account for the observed delay in radial expansion. In addition, the number of neocortical founder cells, i.e., precursors present just before neuronogenesis begins, is reduced by 26% in Ts16 mice, leading to a reduction in overall cortical size at the end of Ts16 neuronogenesis. Thus, altered proliferative characteristics during Ts16 neuronogenesis result in a delay in the generation of neocortical neurons, whereas the founder cell deficit leads to a proportional reduction in the overall number of neurons. Such prenatal perturbations in either the timing of neuron generation or the final number of neurons produced may lead to significant neocortical abnormalities such as those found in DS.

Key words: development; neocortex; trisomy 16; neuronogenesis; Down syndrome; proliferation; programmed cell death; apoptosis

---

Copyright © 2000 Society for Neuroscience  0270-6474/00/20114156-09$05.00/0

This article has been cited by other articles:

				C. B. Dugani, A. Paquin, M. Fujitani, D. R. Kaplan, and F. D. Miller p63 Antagonizes p53 to Promote the Survival of Embryonic Neural Precursor Cells J. Neurosci., May 20, 2009; 29(20): 6710 - 6721. [Abstract] [Full Text] [PDF]

				A.-M. Lepagnol-Bestel, A. Zvara, G. Maussion, F. Quignon, B. Ngimbous, N. Ramoz, S. Imbeaud, Y. Loe-Mie, K. Benihoud, N. Agier, et al. DYRK1A interacts with the REST/NRSF-SWI/SNF chromatin remodelling complex to deregulate gene clusters involved in the neuronal phenotypic traits of Down syndrome Hum. Mol. Genet., April 15, 2009; 18(8): 1405 - 1414. [Abstract] [Full Text] [PDF]

				G. Estivill-Torrus, P. Llebrez-Zayas, E. Matas-Rico, L. Santin, C. Pedraza, I. De Diego, I. Del Arco, P. Fernandez-Llebrez, J. Chun, and F. R. De Fonseca Absence of LPA1 Signaling Results in Defective Cortical Development Cereb Cortex, April 1, 2008; 18(4): 938 - 950. [Abstract] [Full Text] [PDF]

				L. Chakrabarti, Z. Galdzicki, and T. F. Haydar Defects in Embryonic Neurogenesis and Initial Synapse Formation in the Forebrain of the Ts65Dn Mouse Model of Down Syndrome J. Neurosci., October 24, 2007; 27(43): 11483 - 11495. [Abstract] [Full Text] [PDF]

				J. M. Gohlke, W. C. Griffith, and E. M. Faustman Computational Models of Neocortical Neuronogenesis and Programmed Cell Death in the Developing Mouse, Monkey, and Human Cereb Cortex, October 1, 2007; 17(10): 2433 - 2442. [Abstract] [Full Text] [PDF]

				T. Tarui, T. Takahashi, R.S. Nowakowski, N.L. Hayes, P.G. Bhide, and V.S. Caviness Overexpression of p27Kip1, Probability of Cell Cycle Exit, and Laminar Destination of Neocortical Neurons Cereb Cortex, September 1, 2005; 15(9): 1343 - 1355. [Abstract] [Full Text] [PDF]

				R. D. Hodge, A. J. D'Ercole, and J. R. O'Kusky Insulin-Like Growth Factor-I Accelerates the Cell Cycle by Decreasing G1 Phase Length and Increases Cell Cycle Reentry in the Embryonic Cerebral Cortex J. Neurosci., November 10, 2004; 24(45): 10201 - 10210. [Abstract] [Full Text] [PDF]

				M. Dierssen, R. Benavides-Piccione, C. Martinez-Cue, X. Estivill, J. Florez, G.N. Elston, and J. DeFelipe Alterations of Neocortical Pyramidal Cell Phenotype in the Ts65Dn Mouse Model of Down Syndrome: Effects of Environmental Enrichment Cereb Cortex, July 1, 2003; 13(7): 758 - 764. [Abstract] [Full Text] [PDF]

				A. J. Whitmarsh, C.-Y. Kuan, N. J. Kennedy, N. Kelkar, T. F. Haydar, J. P. Mordes, M. Appel, A. A. Rossini, S. N. Jones, R. A. Flavell, et al. Requirement of the JIP1 scaffold protein for stress-induced JNK activation Genes & Dev., September 15, 2001; 15(18): 2421 - 2432. [Abstract] [Full Text] [PDF]

				T. F. Haydar, F. Wang, M. L. Schwartz, and P. Rakic Differential Modulation of Proliferation in the Neocortical Ventricular and Subventricular Zones J. Neurosci., August 1, 2000; 20(15): 5764 - 5774. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help