Transforming growth factor β1 (TGFβ1) controls dendrite morphology and neuronal connectivity via I-κBα and Hes1. Hippocampal neurons (7 days in vitro (DIV), 40,000 cells/cm2) were treated with TGFβ1 (10 ng/ml) before they were co-transfected with pEGFP and plasmids overexpressing either myc-tagged Hes6 (A) or mutant forms of FLAG-tagged I-κBα (B) for 16 h. The neurons were then processed for immunocytochemistry using anti-EGFP and anti-myc/anti-FLAG antibodies. (A) Overexpression of Hes6, a known inhibitor of Hes1, abrogated the effects of TGFβ1 on dendritic length (left panel) and on the number of primary dendrites (middle panel). Hes6 overexpression also prevented the TGFβ1-induced increase in the number of GABAergic terminals (right panel). (B) Transfection of I-κBα S32-36A (a mutation that affects serine phosphorylation of the inhibitor) prevented the TGFβ1-induced increase in dendritic length (left panel) and attenuated the formation of vesicular inhibitory amino acid transporter (VIAAT)-positive clusters (right panel). The I-κBα Y42F mutation that affects the tyrosine phosphorylation of the inhibitor had no effect on TGFβ1 activity. *P < 0.05, **P < 0.01, and ***P < 0.001.
Chacón and Rodríguez-Tébar Alzheimer's Research & Therapy 2012 4:31 doi:10.1186/alzrt134