CIRM supported study finds that a gene associated with autism influences brain stem cells

Dr. Bennett Novitch, UCLA Broad Stem Cell Research Center
Image Credit: UCLA Broad Stem Cell Research Center

In a previous blog post, we discussed new findings in a CIRM supported study at the Salk Institute for Autism Spectrum Disorder (ASD), a developmental disorder that comes in broad ranges and primarily affects communication and behavior.

This week, a new study, also supported by CIRM, finds that a gene associated with ASD, intellectual disability, and language impairment can affect brain stem cells, which in turn, influence early brain development. Dr. Bennett Novitch and his team at UCLA evaluated a gene, called Foxp1, which has been previously studied for its function in the neurons in the developing brain.

Image showing brain cells with lower levels of Foxp1 function (left) and higher levels (right). neural stem cells are stained in green; secondary progenitors and neurons in red.
Image Credit: UCLA Broad Stem Cell Research Center

In this study, Dr. Novitch and his team looked at Foxp1 levels in the brains of developing mouse embryos. What they discovered is that, in normal developing mice the gene was active much earlier than previous studies had indicated. It turns out that the gene was active during the period when neural stem cells are just beginning to expand in numbers and generate a subset of brain cells found deep within the developing brain.

When mice lacked the gene entirely, there were fewer neural stem cells at early stages of brain development, as well as fewer brain cells deep within the developing brain. Alternatively, when the levels of the gene were above normal, the researchers found significantly more neural stem cells and brain cells deep within the developing brain. Additionally, higher levels of the neural stem cells were observed in mice with high levels of the gene even after they were born.

In a press release from UCLA, Dr. Novitch explains how the different levels of the gene can be tied to the variation of Foxp1 levels seen in ASD patients.

“What we saw was that both too much and too little Foxp1 affects the ability of neural stem cells to replicate and form certain neurons in a specific sequence in mice. And this fits with the structural and behavioral abnormalities that have been seen in human patients.”

The full study was published in Cell Reports.

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