For Scientists


FOXG1 Research Group is providing rolling grants to scientists to understand the biology of FOXG1, with the ultimate goal of identifying innovative therapeutic strategies. Click here to access our research presentation detailing what FOXG1 Research Group is looking to fund and current assets available for scientists.

 
 

Please email questions or completed application to
nasha@foxg1research.org


Why is FOXG1 Promising for Research?

We know:

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  • Affected Gene
  • Emerging genotype-phenotype correlation,
  • with patients sharing strong similarities
  • Strong research connecting FOXG1 to prevalent neuropsychiatric disorders
  • How to safely deliver drug/gene therapies to the brain

    Current Assets for Investigators

    • Publicly available FOXG1 deletion mouse models and iPSC lines for molecular/behavioural research and preclinical trials (please see research presentation for more details)
    • FOXG1 clinics at Boston Children’s Hospital and Stanford Children’s Health to accumulate accurate clinical data
    • Rett-associated Natural History Study to characterize outcomes across patients lifespan, and to explore possible genotype-phenotype correlations
    • Active social network of affected families that can be reached immediately
    • Development of a public-facing clinical and patient derived database

    Functional/regulatory elements in FOXG1

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    • All pathogenic missense mutations thought to occur in the forkhead DNA binding domain
    • Deletions including cis-acting regulatory elements but not coding region result in a FOXG1 syndrome phenotype

    FOXG1 and brain development

    Development of the Telencephalon:

    • FOXG1 is required for patterning the developing telencephalon, particularly for ‘ventral identity’ – ‘ventral’ denotes a region of the developing telencephalon that will become the basal ganglion
    • The pattern of FOXG1 expression in the developing telencephalon is a gradient – an abnormal ‘ventral’ region leads to corresponding defects in the opposite ‘dorsal’ region

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    • Mice engineered to lack FOXG1 expression show gross malformations of the cerebral cortex, with a smaller, irregularly shaped cortex, and nearly absent ventral telencephalon

    Neurogenesis and Cell Proliferation:

    • FOXG1 plays a role in the timing of neurogenesis and patterning of the cerebral cortex:

      • FOXG1 suppresses early-neuronal cell types – allows for switch to neurons that reside in deeper layers of the cerebral cortex
    • Several publications support a role for Foxg1 in improving survival of neuronal progenitor cells (early cell types that give rise to neurons)

      • Some evidence to suggest that this does NOTrequire the DNA-binding activity of FOXG1
      • Possible avenue to explore genotype-phenotype correlations

    Unlocking the mysteries of common neurodevelopmental disorders via FOXG1

    Autism spectrum disorders: Proportion Monogenic – 15-34%

    • FOXG1 variant identified in an individual with ASD and his similarly affected mother
    • FOXG1 gene dose associated with ASD diagnosis

    Schizophrenia: Proportion Monogenic heritability 70-80%

    • A schizophrenia-associated loci was shown to physically interact with and regulate FOXG1 expression
    • Expression of schizophrenia-associated gene, GRID1, found to be significantly elevated in FOXG1 patient-derived iPSC neurons and Foxg1+/- fetal mouse brain
    • Epilepsy: Proportion Monogenic – >40% in epileptic encephalopathies

    • ~87% of individuals with a FOXG1 mutation are diagnosed with epilepsy
    • Age of onset, seizure type, response to medication variable