Autism spectrum disorders are neurodevelopmental conditions with diverse aetiologies, all characterized by common core symptoms such as impaired social skills and communication, as well as repetitive behaviour. Cell adhesion molecules, receptor tyrosine kinases and associated downstream signalling have been strongly implicated in both neurodevelopment and autism spectrum disorders. We found that downregulation of the cell adhesion molecule NEGR1 or the receptor tyrosine kinase fibroblast growth factor receptor 2 (FGFR2) similarly affects neuronal migration and spine density during mouse cortical development in vivo and results in impaired core behaviours related to autism spectrum disorders. Mechanistically, NEGR1 physically interacts with FGFR2 and modulates FGFR2-dependent extracellular signal-regulated kinase (ERK) and protein kinase B (AKT) signalling by decreasing FGFR2 degradation from the plasma membrane. Accordingly, FGFR2 overexpression rescues all defects due to Negr1 knockdown in vivo. Negr1 knockout mice present phenotypes similar to Negr1-downregulated animals. These data indicate that NEGR1 and FGFR2 cooperatively regulate cortical development and suggest a role for defective NEGR1-FGFR2 complex and convergent downstream ERK and AKT signalling in autism spectrum disorders.
Introduction: Autism spectrum disorder (ASD) is a prevalent and complex neurodevelopmental disorder (NDD) with genetic and environmental origins. Currently, there are no effective pharmacological treatments targeting core ASD features. This leads to unmet medical needs of individuals with ASD and requires relevant human disease models recapitulating genetic and clinical heterogeneity to better understand underlying mechanisms and identify potential pharmacological therapies.
Background: Individuals with autism spectrum disorder (ASD) exhibit persistent deficits in social interaction and communication in adulthood. Pioneering studies have suggested that these difficulties arise from a lack of immediate, spontaneous mentalizing (i.e.
Background: Thyroid hormones (THs) are essential for brain development. Numerous studies have identified significant links between thyroid dysfunction and cognitive function. However, research on the significance and necessity of thyroid function tests in diagnosis of neurological disorders is limited and subject to controversy.
Introduction: Pediatric neurology provides care for children with complex developmental disorders with environmental, genetic, metabolic, and teratogenic etiologies. Common neurodevelopmental conditions include attention-deficit hyperactivity disorder (ADHD), and autism spectrum disorder. However, only minimal attention from pediatric neurology journals has been devoted to fetal alcohol spectrum disorder.
Social smiling is the earliest gained social communication skill, emerging around 2 months of age. From 2 to 6-months, infants primarily smile in response to caregivers. After 6 months, infants coordinate social smiles with other social cues to initiate interactions with the caregiver.
