A critical period in cortical interneuron neurogenesis in down syndrome revealed by human neural progenitor cells.
Down syndrome (DS) is a developmental disorder whose mental impairment is due to defective cortical development. Human neural progenitor cells (hNPCs) derived from fetal DS cortex initially produce normal numbers of neurons, but generate fewer neurons with time in culture, similar to the pattern of neurogenesis that occurs in DS in vivo. Microarray analysis of DS hNPCs at this critical time reveals gene changes indicative of defects in interneuron progenitor development. In addition, dysregulated expression of many genes involved in neural progenitor cell biology points to changes in the progenitor population and subsequent reduction in interneuron neurogenesis. Delineation of a critical period in interneuron development in DS provides a foundation for investigation of the basis of reduced neurogenesis in DS and defines a time when these progenitor cells may be amenable to therapeutic treatment.
Bhattacharyya
Anita
A
Stem Cell Research Group, The Waisman Center, University of Wisconsin, Madison, Wisc. 53705, USA. bhattacharyy@waisman.wisc.edu
McMillan
Erin
E
Chen
Serene I
SI
Wallace
Kyle
K
Svendsen
Clive N
CN
D002452:Cell Count; D016923:Cell Death; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000378:metabolism / Q000503:physiopathology*; D004314:Down Syndrome / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D005333:Fetus; D005455:Fluorescent Antibody Technique; D015870:Gene Expression / Q000235:genetics*; D020869:Gene Expression Profiling; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D007395:Interneurons / Q000378:metabolism / Q000502:physiology*; D039902:Multipotent Stem Cells; D055495:Neurogenesis / Q000235:genetics / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D050598:Vesicular Glutamate Transport Protein 1 / Q000378:metabolism; D050495:Vesicular Inhibitory Amino Acid Transport Proteins / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
C493464:SLC17A7 protein, human; C492245:SLC32A1 protein, human; D050598:Vesicular Glutamate Transport Protein 1; D050495:Vesicular Inhibitory Amino Acid Transport Proteins; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid