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Monday, August 10, 2009

Ethanol Affects Transforming Growth Factor β1-Initiated Signals: Cross-Talking Pathways in the Developing Rat Cerebral Wall
The Journal of Neuroscience, July 29, 2009, 29(30):9521-9533

TGFβ1 regulates early cortical development by moving young neurons from the proliferative population and promoting their migration. Altered TGFβ1-regulated signaling can lead to abnormal development underlying microencephaly and migratory defects as in attention deficit hyperactivity disorder, dyslexia, and fetal alcohol spectrum disorder.

The present study tested the hypotheses that TGFβ1 signals through cross-talking Smad2/3 and extracellular signal-regulated kinase 1/2 (ERK1/2) pathways and that ethanol simulates these TGFβ1-initiated signals.

In summary, TGFβ1 activates two separate pathways (Smad2/3 and ERK1/2) that actively interact. Ethanol simulates TGFβ1-induced changes in these signaling systems. Each pathway is preferentially activated during specific developmental events: the Smad2/3 pathway is key for cells exiting from the cycling population and the ERK1/2 pathway is particularly inducible during neuronal migration.


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