Integrator Genes Play Key Role In Brain Development

Researchers in Singapore have demonstrated that integrator genes help prevent the de-differentiation of neurons in the brain.

AsianScientist (May 8, 2019) – A study by the Duke-National University of Singapore Medical School (Duke-NUS), Singapore, has revealed how healthy brain development in fruit flies is regulated by a multiprotein ‘integrator complex’. Their findings are published in the journal Cell Reports.

Mutations in human integrator genes intS1 and intS8 are known to be associated with neurodevelopmental syndrome, which is characterized by profound intellectual disability, epilepsy and subtle structural brain abnormalities. However, the role of the integrator complex during brain development is not well understood.

In the present study, researchers led by Associate Professor Wang Hongyan at Duke-NUS examined members of the integrator complex in fruit fly brains to understand their roles in the development of the nervous system. When her team mutated and turned off members of the integrator complex in the fruit fly brains, they observed abnormal neural stem cells forming.

Turning off several integrator genes in intermediate neural progenitor cells led to excessive formation of neural stem cells, highlighting the role of integrator proteins in preventing intermediate neural progenitors from de-differentiating into neural stem cells. The researchers further identified Earmuff, a transcription factor, as the primary target of integrator complex proteins in brain cells.

The findings highlight the critical and novel roles played by integrator complex proteins in preventing de-differentiation, and thus in promoting brain development in fruit flies.

“Given that integrator proteins and Earmuff are highly conserved in flies and humans, our study will facilitate understanding the function of their mammalian and human counterparts during brain development, in addition to understanding potential disease mechanisms,” said Wang.

Professor Patrick Casey, senior vice dean of research at Duke-NUS, added that these findings provide valuable insights to better understand and treat neurodegenerative diseases in the future.

The article can be found at: Zhang et al. (2019) The Integrator Complex Prevents Dedifferentiation of Intermediate Neural Progenitors back into Neural Stem Cells.


Source: Duke-NUS Medical School; Photo: Zhang & Koe.
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