citation for the above?

Neural precursor cell proliferation is disrupted through activation of
the aryl hydrocarbon receptor by 2,3,7,8-tetrachlorodibenzo-p-dioxin.
Neurogenesis involves the proliferation of multipotent neuroepithelial
stem cells followed by differentiation into lineage-restricted neural
precursor cells (NPCs) during the embryonic period. Interestingly,
these progenitor cells express robust levels of the aryl hydrocarbon
receptor (AhR), a ligand-activated transcription factor that regulates
expression of genes important for growth regulation, and xenobiotic
metabolism. Upon binding 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a
pervasive environmental contaminant and potent AhR ligand, AhR, is
activated and disrupts gene expression patterns to produce cellular
toxicity. Because of its widespread distribution in the brain during
critical proliferative phases of neurogenesis, it is conceivable that
AhR participates in NPC expansion. Therefore, this study tested the
hypothesis that AhR activation by TCDD disrupts signaling events that
regulate NPC proliferation. The C17.2 NPC line served as a model
system to (1) assess whether NPCs are targets for TCDD-induced
neurotoxicity and (2) characterize the effects of TCDD on NPC
proliferation. We demonstrated that C17.2 NPCs express an intact AhR
signaling pathway that becomes transcriptionally active after TCDD
exposure. (3)H-thymidine and alamar blue reduction assays indicated
that TCDD suppresses NPC proliferation in a concentration-dependent
manner without the loss of cell viability. Cell cycle distribution
analysis by flow cytometry revealed that TCDD-induced growth arrest
results from an impaired G1 to S cell cycle transition. Moreover, TCDD
exposure altered p27( kip1) and cyclin D1 cell cycle regulatory
protein expression levels consistent with a G1 phase arrest. Initial
studies in primary NPCs isolated from the ventral forebrain of
embryonic mice demonstrated that TCDD reduced cell proliferation
through a G1 phase arrest, corroborating our findings in the C17.2
cell line. Together, these observations suggest that the inappropriate
or sustained activation of AhR by TCDD during neurogenesis can
interfere with signaling pathways that regulate neuroepithelial stem
cell/NPC proliferation, which could adversely impact final cell number
in the brain and lead to functional impairments. PMID: 20486776