siRNA-mediated downregulation of Fgr2 in mice resulted in abnormal neuronal migration and spine density during cortical development, as well as reduced ultrasonic vocalizations and impaired social interactions; conversely, overexpression of FGFR2 was shown to rescue neuronal migration and spine defects and ASD-related core behaviors in Negr1-downregulated mice (Szczurkowska et al., 2018).
Molecular Function
Tyrosine-protein kinase that acts as cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of cell proliferation, differentiation, migration and apoptosis, and in the regulation of embryonic development.
External Links
References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
NEGR1 and FGFR2 cooperatively regulate cortical development and core behaviours related to autism disorders in mice.
In utero electroporation of Fgfr2 siRNA at E15.5 impairs the radial migration and spine density of pyramidal neurons in the somatosensory cortex, reduces usv calls, decreases pain perception and social sniffing and increases self grooming (PMID 30059965).
References
Type
Title
Author, Year
Primary
NEGR1 and FGFR2 cooperatively regulate cortical development and core behaviours related to autism disorders in mice.
Model Type:
Genetic
Model Genotype:
NA
Mutation:
E15.2 timed-pregnant CD1 mice were injected with Fgfr2 siRNA in Fast Green dye through the uterine wall into the lateral ventricle of each embryo and electroporated into the subventricular cortex. Co-electroporation of td-Tomato or EGFP was used to visualize transfected neurons and normalize total DNA transfected.
Allele Type: Knockdown
Strain of Origin: CD1
Genetic Background: CD1
ES Cell Line: Mutant ES Cell Line: Model Source: Charles River, SRL
Model Type:
Genetic
Model Genotype:
NA
Mutation:
E15.2 timed-pregnant CD1 mice were injected with Fgfr2 siRNA in Fast Green dye through the uterine wall into the lateral ventricle of each embryo and electroporated into the visual cortex. Co-electroporation of td-Tomato or EGFP was used to visualize transfected neurons and normalize total DNA transfected.
Allele Type: Knockdown
Strain of Origin: CD1
Genetic Background: CD1
ES Cell Line: Mutant ES Cell Line: Model Source: Charles River, SRL
Model Type:
Genetic
Model Genotype:
NA
Mutation:
E15.2 timed-pregnant CD1 mice were injected with Fgfr2 siRNA in Fast Green dye through the uterine wall into the lateral ventricle of each embryo and electroporated into the somatosensory and motor cortices. Co-electroporation of td-Tomato or EGFP was used to visualize transfected neurons and normalize total DNA transfected.
Allele Type: Knockdown
Strain of Origin: CD1
Genetic Background: CD1
ES Cell Line: Mutant ES Cell Line: Model Source: Charles River, SRL
Model Type:
Genetic
Model Genotype:
NA
Mutation:
E15.2 timed-pregnant CD1 mice were injected with Fgfr2 siRNA in Fast Green dye through the uterine wall into the lateral ventricle of each embryo and electroporated into the prefrontal cortex. Co-electroporation of td-Tomato or EGFP was used to visualize transfected neurons and normalize total DNA transfected.
Allele Type: Knockdown
Strain of Origin: CD1
Genetic Background: CD1
ES Cell Line: Mutant ES Cell Line: Model Source: Charles River, SRL
Model Type:
Genetic
Model Genotype:
NA
Mutation:
E15.2 timed-pregnant CD1 mice were injected with Fgfr2 cDNA in Fast Green dye through the uterine wall into the lateral ventricle of each embryo and electroporated into the somatosensory cortex. Co-electroporation of td-Tomato or EGFP was used to visualize transfected neurons and normalize total DNA transfected.
Allele Type: Knockdown
Strain of Origin: CD1
Genetic Background: CD1
ES Cell Line: Mutant ES Cell Line: Model Source: Charles River, SRL
Dendritic architecture: dendritic tree complexity1
Decreased
Description: Fgfr2 knockdown neurons in layer ii/iii of the somatosensory cortex and ectopic neurons stuck in layer v show decrease in the number of dendritic branches compared to controls.
Exp Paradigm: NA
Description: Fgfr2 knockdown neurons that were stuck in layer v at p7 retained markers of the upper layers ii/iii (cux1) indicating mis-specification of cortical layer specific neurons.
Exp Paradigm: NA
Description: Fgfr2 knockdown neurons were mostly located in the ventricular zone and intermediate zone, with only a small percentage reaching the cortical plate at e18 whereas control scrambled sirna cells were distributed across the ventricular zone, intermediate zone, and cortical plate, indicating reduced radial migration of fgfr2 knockdown neurons. fgfr2 knockdown neurons were stuck in layer v and did not cross the border between layer iv/v by p7 or p35, whereas most control sirna transfected neurons migrated into layer ii/ii. fgfr2 knockdown neurons of upper cortical layers accumulated in lower suregions compared to controls.
Exp Paradigm: NA
Description: Fgfr2 knockdown neurons with electroporation targeting neurons in the visual cortex show decrease in spine density compared to controls.
Exp Paradigm: NA
Description: Fgfr2 knockdown neurons were ectopically located in the visual cortex and mis-positioned in layer ii/iii compared to controls.
Exp Paradigm: NA
Description: Fgfr2 knockdown neurons in the motor and somatosensory cortices were ectopically located in layer v compared to controls. defect is neuronal migration was higher in the somatosensory cortex than in the motor cortex.
Exp Paradigm: NA
Description: Fgfr2 knockdown neurons with electroporation targeting layer ii/iii neurons in the somatosensory cortex show decrease in spine density compared to controls.
Exp Paradigm: NA
Description: Pups transfected with fgfr2 sirna in the somatosensory cortex show increased latency in removing paw from hot plate compared to controls.
Exp Paradigm: NA
Description: Pups transfected with fgfr2 sirna into the somatosensory cortex show decrease in ultrasonic vocalizations compared to controls.
Exp Paradigm: NA
