Protein Found Essential for Brain Development

Lissencephaly may be associated with other diseases, including isolated lissencephaly sequence, Miller-Dieker syndrome (MDS), and Walker-Warburg syndrome.

LIS1 (which stands for Lissencephaly-1) is a gene that is deleted or mutated on a chromosomal region of chromosome 17 (called 17p13.3) in many children with lissencephaly. LIS1 resides fairly close to the 14-3-3 epsilon gene on this chromosome. Patients with lissencephaly only have deletions of one copy of LIS1, but never 14-3-3 epsilon, while patients with MDS have deletions of both genes on the same chromosome.

In a new study published June 8, 2003, in the online edition of Nature Genetics, investigators at the University of California, San Diego (USA; www.uscd.edu), established a crucial role for 14-3-3 epsilon in neuronal development in sustaining the effects of CDK5 phosphorylation and provided a molecular explanation for the differences in severity of human neuronal migration defects with 17p13.3 deletions.

Senior author Dr. Anthony Wynshaw-Boris explained, "This is the first demonstration in mammals that 14-3-3 epsilon is essential for brain development. We also showed that the gene is always deleted on one chromosome in patients with a rare but severe brain disorder called Miller-Dieker syndrome (MDS). Not only does our study determine a novel function for 14-3-3 epsilon, but it also provides a molecular explanation for why MDS patients have more severe lissencephaly.”



Related Links:
University of California, San Diego