Genese linked to autism and schizophrenia are only switched on
during the early stages of brain development, according to a
collaboration between researchers at Imperial College London, the
University of Oxford and King's College London.
This new study adds to the evidence that autism and
schizophrenia are neurodevelopmental disorders, a term describing
conditions that originate during early brain
development.
The researchers studied gene expression in the brains of
mice throughout their development, from 15-day-old embryos to
adults.
The research focused on cells in the 'subplate', a region
of the brain where the first neurons (nerve cells) develop.
Subplate neurons are essential to brain development, and provide
the earliest connections within the brain.
"The subplate provides the scaffolding required for a
brain to grow, so is important to consider when studying brain
development," said Professor Zoltán Molnár from the University of
Oxford.
"Looking at the pyramids in Egypt today doesn't tell us
how they were actually built. Studying adult brains is like looking
at the pyramids today, but by studying the developing brains we are
able to see the transient scaffolding that has been used to
construct it."
The study shows that certain genes linked to autism and
schizophrenia are only active in the subplate during specific
stages of development. The data analysis was designed by Dr Enrico
Petretto at Imperial College London.
Dr Petretto explained: "We looked at the full network of
genes in the brain to identify which pathways play a role in early
brain development. This allowed us to find coherent clusters of
genes previously associated with susceptibility to autism spectrum
disorders or schizophrenia. These results provide a unique resource
for our understanding of how gene behaviour changes in the mouse
subplate from the early embryonic stage to adulthood. This means we
are better equipped to investigate how the gene network changes in
the developing brain and identify any links with neurodevelopmental
disorders."
The team was able to map gene activity in full detail
thanks to new methods which allowed them to dissect and profile
gene expression from small numbers of cells. This also enabled them
to identify the different populations of subplate neurons more
accurately.
The paper, Expression profiling
of mouse subplate reveals a dynamic gene network and disease
association with autism and schizophrenia, is
published in Proceedings of the National Academy of
Sciences.