title: Tsc1 haploinsufficiency is sufficient to increase dendritic patterning and Filamin A levels.
abstract: Most individuals with tuberous sclerosis complex (TSC) are born with a mutant allele of either TSC1 or TSC2 and a mosaic of psychological and cognitive defects. Tsc1 loss of heterozygosity contributes to severe dendritic abnormalities that are rescued by normalizing the levels of the actin-cross linking protein, Filamin A (FLNA). However, it is unclear whether dendrites and FLNA levels are abnormal in an heterozygote Tsc1 condition. Here, we examined dendritic morphology and FLNA levels in the olfactory bulb of Tsc1 wild type and heterozygote mice. Using in vivo neonatal electroporation to label newborn neurons followed by sholl analysis, we found that Tsc1 haploinsufficiency is associated with increased dendritic complexity and total dendritic length as well as increased FLNA levels. Since reducing FLNA levels has been shown to decrease Tsc1(+/-) dendritic complexity, these data suggest that increased FLNA levels in Tsc1(+/-) mice contribute to abnormal dendritic patterning in the Tsc1 heterozygote condition of individuals with TSC.
authors.affiliation: Department of Neurosurgery, Xiangya Hospital, Central South University, 85 Xiangya Street, Changsha, 410008, China; Departments of Neurosurgery, and Cellular & Molecular Physiology, Yale University School of Medicine, 333 Cedar Street, New Haven, CT, 06520-8082, USA.
authors.forename: Longbo
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, Xiangya Hospital, Central South University, 85 Xiangya Street, Changsha, 410008, China; Departments of Neurosurgery, and Cellular & Molecular Physiology, Yale University School of Medicine, 333 Cedar Street, New Haven, CT, 06520-8082, USA.
authors.forename: Tianxiang
authors.initials: T
authors.lastname: Huang
authors.affiliation: Departments of Neurosurgery, and Cellular & Molecular Physiology, Yale University School of Medicine, 333 Cedar Street, New Haven, CT, 06520-8082, USA. Electronic address: angelique.bordey@yale.edu.
authors.forename: Angélique
authors.initials: A
authors.lastname: Bordey
mesh_terms: D000818:Animals; D003712:Dendrites / Q000235:genetics* / Q000473:pathology*; D064448:Filamins / Q000378:metabolism*; D057895:Haploinsufficiency; D051379:Mice; D008822:Mice, Transgenic; D009830:Olfactory Bulb / Q000378:metabolism / Q000473:pathology; D014402:Tuberous Sclerosis / Q000235:genetics*; D000077004:Tuberous Sclerosis Complex 1 Protein; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D064448:Filamins; C529499:FlnA protein, mouse; C000624651:Tsc1 protein, mouse; D000077004:Tuberous Sclerosis Complex 1 Protein; D025521:Tumor Suppressor Proteins
keywords: Circuit; Dendrite; Filamin A; Network; Neurogenesis; Tuberous sclerosis complex; mTOR