Faculty Bibliography

Neurogenins are proneural transcription factors required to specify neuronal identity. Their overexpression in human pluripotent stem cells rapidly produces cortical-like neurons with spiking activity and, because of this, they have been widely adopted for human neuron disease models. However, we do not fully understand the key downstream regulatory effectors responsible for driving neural differentiation. Here, using inducible expression of NEUROG1 and NEUROG2, we identify transcription factors (TFs) required for directed neuronal differentiation by combining expression and chromatin accessibility analyses with a pooled in vitro CRISPR-Cas9 screen targeting all ~1900 TFs in the human genome. The loss of one of these essential TFs (ZBTB18) yields few MAP2-positive neurons. Differentiated ZBTB18-null cells have radically altered gene expression, leading to cytoskeletal defects and stunted neurites and spines. In addition to identifying key downstream TFs for neuronal differentiation, our work develops an integrative multi-omics and TFome-wide perturbation platform to rapidly characterize essential TFs for the differentiation of any human cell type.

BACKGROUND/UNASSIGNED:Internet overuse is an emerging public health emergency, especially for college students in the United States. The purpose of this study was to assess college students' internet usage and interest in learning healthy internet usage skills as part of a college curriculum. STUDY DESIGN/UNASSIGNED:Participants completed an online anonymous questionnaire which included the short version of the Internet Addiction Test, a modified Youth Health Movement survey, and questions regarding their interest in healthy internet use coursework. METHODS/UNASSIGNED:A total of 402 participants were recruited via an email LISTSERV of current undergraduates and recent graduates who had taken at least one class within a child and adolescent mental health studies minor while enrolled in a large university. RESULTS/UNASSIGNED:Overall, 70% of participants reported that they use the internet excessively, and a majority of participants reported that internet use has negatively affected their sleep and increased their anxiety. Seventy percent of participants reported that they would benefit from instruction on healthy internet usage via formal courses for credit or online modules. CONCLUSIONS/UNASSIGNED:Students are aware of the difficulty in managing their internet use in college and are motivated to engage in novel courses on healthy internet usage. Academic institutions should consider developing courses or modules on healthy internet use.

Alzheimer disease (AD) is the most common cause of dementia in older individuals. AD is characterized pathologically by amyloid-β (Aβ) plaques and tau neurofibrillary tangles in the brain, with associated loss of synapses and neurons, which eventually results in dementia. Many of the early attempts to develop treatments for AD focused on Aβ, but a lack of efficacy of these treatments in terms of slowing disease progression led to a change of strategy towards targeting of tau pathology. Given that tau shows a stronger correlation with symptom severity than does Aβ, targeting of tau is more likely to be efficacious once cognitive decline begins. Anti-tau therapies initially focused on post-translational modifications, inhibition of tau aggregation and stabilization of microtubules. However, trials of many potential drugs were discontinued because of toxicity and/or lack of efficacy. Currently, the majority of tau-targeting agents in clinical trials are immunotherapies. In this Review, we provide an update on the results from the initial immunotherapy trials and an overview of new therapeutic candidates that are in clinical development, as well as considering future directions for tau-targeting therapies.

Social behaviors are innate and supported by dedicated neural circuits, but the molecular identities of these circuits and how they are established developmentally and shaped by experience remain unclear. Here we show that medial amygdala (MeA) cells originating from two embryonically parcellated developmental lineages have distinct response patterns and functions in social behavior in male mice. MeA cells expressing the transcription factor Foxp2 (MeA^Foxp2) are specialized for processing male conspecific cues and are essential for adult inter-male aggression. By contrast, MeA cells derived from the Dbx1 lineage (MeA^Dbx1) respond broadly to social cues, respond strongly during ejaculation and are not essential for male aggression. Furthermore, MeA^Foxp2 and MeA^Dbx1 cells show differential anatomical and functional connectivity. Altogether, our results suggest a developmentally hardwired aggression circuit at the MeA level and a lineage-based circuit organization by which a cell's embryonic transcription factor profile determines its social information representation and behavioral relevance during adulthood.