A team of researchers has identified a signaling pathway key for normal brain development in the mouse. The team was led by Pierre Gressens, at Inserm U676, Paris, France, and Vincent Lelièvre, at CNRS UPR-3212, Strasbourg, France.
Of paramount importance, the data generated suggest that environmental factors, including maternal ones, can influence the final size of the brain.
Individuals with microcephaly primary hereditary (MCPH) are born with a very small head and a small brain. They suffer mild developmental delay, hyperkinesia (excessive restlessness), and mild to severe cognitive impairment. Although mutation of any one of seven genes is known to cause MCPH, a lack of good animal models has made it hard to understand the underlying mechanisms. To gain insight into this, Gressens, Lelièvre, and colleagues used a mouse model in which microcephaly is induced by blocking the peptide VIP during gestation using a VIP antagonist (VA). Initial analysis indicated that prenatal administration of VA gives rise to brain abnormalities that mimic those observed in patients with MCPH. Further analysis identified a cellular and molecular mechanism for the observed abnormalities. The authors therefore conclude that the identified molecular pathway (the VIP/Mcph1/Chk1 pathway) is key for normal brain development and suggest that environmental factors disturbing this pathway can modulate the development of the brain as well as its final size.