Topic: PTEN

The brain is comprised of a remarkable cell-type diversity, which arises during embryonic and fetal development from neural stem cells and provides the basis for proper brain function. Production errors in the tightly orchestrated process of brain development can result in neurodevelopmental malformations. Alterations in the mTOR pathway result in a spectrum of defects ranging from focal cortical dysplasia to hemimegalencephaly (HME). HME is a rare disorder, characterized by the enlargement of one hemisphere. To date, a detailed cellular and molecular understanding of the neuropathological und

Autism spectrum disorder (ASD) is a term used to describe a wide variety of neurodevelopmental disorders that share manifestations and symptoms including intellectual disabilities, social impairments, delayed speech development and repetitive behaviors. Different animal models of ASD share similar electrophysiological and morphological aberrations at the neuronal level. In particular, previous studies have shown that the developmental maturation of GABAergic circuitry appears altered leading to an excitation/inhibition imbalance in the adult. During neurotransmission, the polarity of the GABAe

Autism spectrum disorder (ASD) is a complex and highly prevalent neurodevelopmental disorder. ASD exhibits significant heterogeneity in genotypes and phenotypes. In recent years, dysregulation of protein synthesis has emerged as a converging mechanism in ASD. Here, to explore altered translation in ASD, we used induced pluripotent stem cells (iPSCs) which have emerged as a promising cellular tool for disease modeling. Patient relevant mutations in FMR1, PTEN, and TSC2, that cause dysregulated protein synthesis, were introduced into iPSCs derived from healthy donors via CRISPR/Cas9. Then, iPSCs

Down syndrome (DS) individuals are characterized by a variety of pathological phenotypes that manifest with wide variability in different tissues. In the central nervous system, the accelerated aging phenotype is associated with the risk of developing Alzheimer-like dementia. A central aspect of neurodegeneration is the close association between metabolic disorders and cognitive decline. Multiple studies have suggested a link between metabolic disorder and microRNAs (miR), small non-coding RNAs acting as post-transcriptional regulators of a plethora of genes. Among triplicated miRNAs on chromo

The neocortex is an architecturally complex structure composed of a diverse population of neurons and glia. This well-defined structure and cellular diversity can be attributed to the tightly regulated and highly ordered cortical development program. PTEN mutations in humans typically result in severe macrocephaly, increased susceptibility to a variety of cancers, and Autism Spectrum Disorder (ASD). Here we explore the role of Pten in cortical development at single-cell resolution by utilizing Mosaic Analysis with Double Markers (MADM) to sparsely label and perturb Pten in our mouse model. We