Tuesday, 31 July 2018

In BRAIN a new study on two autism-related genes

The work was authored by a research group of the Italian Institute of Technology with CIBIO of UniTrento

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A new study which has been published in the prestigious journal Brain for the first time links defective brain development to autism spectrum disorders.

The study focused on the interaction between two molecules, Negr1 and FGFR2, which ensure the proper development of the somatosensory cortex, a specific area of the brain whose function is to receive and process sensory stimuli.

The researchers have discovered that the alteration of the functionality of Negr1 and FGFR2 generates impairments in the cerebral cortex and causes abnormal behaviours that are consistent with the symptoms of autism.

The study was conducted by a research team of the IIT-Italian Institute of Technology, led by Laura Cancedda, in collaboration with the Laboratoriy of Biology of Synapses of the Centre for Integrative Biology (CIBIO) of the University of Trento, led by Giovanni Piccoli.

Cancedda and Piccoli are supported by the career programme of the Dulbecco Telethon Institute.

Autism is a neurodevelopmental disorder that appears in the first years of life, characterized by repetitive behaviour and impaired social skills and verbal and non-verbal communication. Its triggering factors are not fully known, but research suggests that genetic and metabolic factors may hamper the physiological maturation of neurons and functional circuits.

The researchers were able to identify the mechanism through which Negr1 and FGFR2 cooperate in regulating the early stages of cerebral development, influencing the migration of neurons within the foetal brain and determining their correct positioning. The researchers downregulated the expression of these genes in specific neuronal populations and observed remarkable effects on the migration and morphological development of those cells: the absence of Negr1 or FGFR2 prevents the migration of neurons to other cortical strata and reduces neurite growth.

Mutations in Negr1 and FGFR2 had already been observed in patients with autism related disorders but scientists did not know if the two genes were somehow connected and how they cooperated to regulate cerebral development. The researchers discovered that gene alteration may be the cause of the connectivity impairments observed in the brains of patients with autism.

This study provides an important piece in the puzzle of knowledge of the development of the nervous system, and it is fundamental to better understand the biological basis of autism and the reasons why microscopic alterations in specific nervous circuits in the cerebral cortex may have a huge impact on its functioning and lead to behavioural disorders.