title: A human neurodevelopmental model for Williams syndrome.
abstract: Williams syndrome is a genetic neurodevelopmental disorder characterized by an uncommon hypersociability and a mosaic of retained and compromised linguistic and cognitive abilities. Nearly all clinically diagnosed individuals with Williams syndrome lack precisely the same set of genes, with breakpoints in chromosome band 7q11.23 (refs 1-5). The contribution of specific genes to the neuroanatomical and functional alterations, leading to behavioural pathologies in humans, remains largely unexplored. Here we investigate neural progenitor cells and cortical neurons derived from Williams syndrome and typically developing induced pluripotent stem cells. Neural progenitor cells in Williams syndrome have an increased doubling time and apoptosis compared with typically developing neural progenitor cells. Using an individual with atypical Williams syndrome, we narrowed this cellular phenotype to a single gene candidate, frizzled 9 (FZD9). At the neuronal stage, layer V/VI cortical neurons derived from Williams syndrome were characterized by longer total dendrites, increased numbers of spines and synapses, aberrant calcium oscillation and altered network connectivity. Morphometric alterations observed in neurons from Williams syndrome were validated after Golgi staining of post-mortem layer V/VI cortical neurons. This model of human induced pluripotent stem cells fills the current knowledge gap in the cellular biology of Williams syndrome and could lead to further insights into the molecular mechanism underlying the disorder and the human social brain.
authors: Thanathom
authors: T
authors: Chailangkarn
authors: Cleber A
authors: CA
authors: Trujillo
authors: Beatriz C
authors: BC
authors: Freitas
authors: Branka
authors: B
authors: Hrvoj-Mihic
authors: Roberto H
authors: RH
authors: Herai
authors: Diana X
authors: DX
authors: Yu
authors: Timothy T
authors: TT
authors: Brown
authors: Maria C
authors: MC
authors: Marchetto
authors: Cedric
authors: C
authors: Bardy
authors: Lauren
authors: L
authors: McHenry
authors: Lisa
authors: L
authors: Stefanacci
authors: Anna
authors: A
authors: Järvinen
authors: Yvonne M
authors: YM
authors: Searcy
authors: Michelle
authors: M
authors: DeWitt
authors: Wenny
authors: W
authors: Wong
authors: Philip
authors: P
authors: Lai
authors: M Colin
authors: MC
authors: Ard
authors: Kari L
authors: KL
authors: Hanson
authors: Sarah
authors: S
authors: Romero
authors: Bob
authors: B
authors: Jacobs
authors: Anders M
authors: AM
authors: Dale
authors: Li
authors: L
authors: Dai
authors: Julie R
authors: JR
authors: Korenberg
authors: Fred H
authors: FH
authors: Gage
authors: Ursula
authors: U
authors: Bellugi
authors: Eric
authors: E
authors: Halgren
authors: Katerina
authors: K
authors: Semendeferi
authors: Alysson R
authors: AR
authors: Muotri
mesh_terms: D000293:Adolescent; D000328:Adult; D017209:Apoptosis; D001921:Brain / Q000473:pathology*; D002118:Calcium / Q000378:metabolism; D002454:Cell Differentiation; D048430:Cell Shape; D065150:Cellular Reprogramming; D002540:Cerebral Cortex / Q000473:pathology; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics; D003712:Dendrites / Q000473:pathology; D005260:Female; D051157:Frizzled Receptors / Q000172:deficiency / Q000235:genetics; D057895:Haploinsufficiency / Q000235:genetics; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000473:pathology; D008297:Male; D008959:Models, Neurological; D058953:Neural Stem Cells / Q000473:pathology; D009474:Neurons / Q000473:pathology; D010641:Phenotype; D015203:Reproducibility of Results; D013569:Synapses / Q000473:pathology; D018980:Williams Syndrome / Q000235:genetics / Q000473:pathology*; D055815:Young Adult
chemical_list: C549560:FZD9 protein, human; D051157:Frizzled Receptors; D002118:Calcium