Neurodevelopmental disorders, including
schizophrenia and autism, likely result from complex
interactions that modify the effects of individual
genes. In a new study, researchers evaluated the
effects of over 300 pairwise knockdowns reducing the
expression of two genes simultaneously of the fruit
fly versions of genes located in a region of human
chromosome 3 that, when deleted, has been implicated
in these disorders. These interactions suggest that
the disorders have a complex causation involving
many genes, rather than resulting from the effects
of any individual gene. One gene in particular,
NCBP2, appears to be a key modifier, influencing the
impact of other genes in the deletion. Of the 21
genes located in the 3q29 deletion, fruit fly
counterparts have been identified for 14 genes.
Using a technique called RNA interference (RNAi),
which reduces the expression of genes in specific
tissues in the fly, the researchers first knocked
down the expression of 14 fly genes individually and
quantified their impact on how cells are organized
in the fly eye. They then looked at pairwise
knockdowns by reducing the expression of two genes
simultaneously. Overall, they tested 314 pairwise
knockdowns, including interactions among all 14 of
the genes in the 3q29 deletion and between those
genes and others with known roles in
neurodevelopment. Among all the pairwise knockdowns
that the research team tested, one particular gene
stood out as having a large effect on the impact of
all the other genes in the 3q29 deletion. The NCBP2
gene codes for a protein that is part of the
"nuclear cap-binding complex," which binds to the
end of RNA molecules and plays a role in RNA
regulation, transport, and decay in the cell. The
main impact of NCBP2 interactions was the disruption
of the cell cycle and increased "apoptosis" cell
death. The researchers propose that NCBP2 could
modify several cellular processes, not necessarily
directly related to apoptosis, but ultimately
causing a cascade of events that lead to cell death.
Thus, the researchers suggest that apoptosis is an
important molecular mechanism for neurodevelopmental
disorders related to the 3q29 deletion. |