Novel role for Fragile X protein in the embryonic brain

16 December 2014

In a collaboration between researchers at KU Leuven and the Meredith group at the CNCR, a recent article in Nature Neuroscience shows developmental delays in cortical brain development prior to birth in a mouse model of the most common inherited form of intellectual disability and autism disorder, Fragile X syndrome.

Fragile X syndrome is the most common cause of inherited intellectual disability, as well as the most frequent monogenic cause of autism spectrum disorders. The syndrome is caused by the absence or incorrect production of the protein FMRP (Fragile X Mental Retardation Protein). Using a genetic mouse model for Fragile X syndrome, many changes in neuronal and synaptic processing in the brain have been reported during juvenile and adult stages. However, it was not known whether such changes caused by lack of FMRP would occur prenatally at a stage when the layers of the cortex are forming.

The authors showed a delay in the transition of neurons to their correct layers in the developing cortex and that lack of FMRP affected levels of the protein N-cadherin, which regulates the maturation of neurons embryonically. These deficits could be rescued if FMRP was re-introduced back into the brain during prenatal stages. Such timed delays in early brain formation were predicted to occur in Fragile X syndrome, according to work by the Meredith group at the CNCR. These latest findings now show such changes occurring in the brain at far earlier stages than previously documented in the mouse model or in people with Fragile X syndrome.

The research was led and coordinated by Professor Claudia Bagni and her team at VIB/KU Leuven (Belgium) and Tor Vergata (Italy). The collaboration between the groups was supported by ‘BrainTrain’, an EU Marie-Curie training programme based at the CNCR ( Authors Giorgio La Fata (VIB/KU Leuven) and Julia Dawitz (INF department, CNCR) were affiliates of the programme, working in host labs of Professor Claudia Bagni and Dr Rhiannon Meredith, respectively.
FMRP regulates multipolar to bipolar transition affecting neuronal migration and cortical circuitry.

La Fata G, Gärtner A, Domínguez-Iturza N, Dresselaers T, Dawitz J, Poorthuis RB, Averna M, Himmelreich U, Meredith RM, Achsel T, Dotti CG, Bagni C.