Higher-order visual thalamus communicates broadly and bi-directionally with primary and extrastriate cortical areas in various mammals. In primates, the pulvinar is a topographically and functionally organized thalamic nucleus that is largely dedicated to visual processing. Still, a more granular connectivity map is needed to understand the role of thalamocortical loops in visually guided behavior. Similarly, the secondary visual thalamic nucleus in mice (the lateral posterior nucleus, LP) has extensive connections with cortex. To resolve the precise connectivity of these circuits, we first mapped mouse visual cortical areas using intrinsic signal optical imaging and then injected fluorescently tagged retrograde tracers (cholera toxin subunit B) into retinotopically-matched locations in various combinations of seven different visual areas. We find that LP neurons representing matched regions in visual space but projecting to different extrastriate areas are found in different topographically organized zones, with few double-labeled cells (~4-6%). In addition, V1 and extrastriate visual areas received input from the ventrolateral part of the laterodorsal nucleus of the thalamus (LDVL). These observations indicate that the thalamus provides topographically organized circuits to each mouse visual area and raise new questions about the contributions from LP and LDVL to cortical activity.

Oligodendrocyte progenitor cells (OPC) undergo asymmetric cell division (ACD) to generate one OPC and one differentiating oligodendrocyte (OL) progeny. Loss of pro-mitotic proteoglycan and OPC marker NG2 in the OL progeny is the earliest immunophenotypic change of unknown mechanism that indicates differentiation commitment. Here, we report that expression of the mouse homolog of Drosophila tumor suppressor Lethal giant larvae 1 (Lgl1) is induced during OL differentiation. Lgl1 conditional knockout OPC progeny retain NG2 and show reduced OL differentiation, while undergoing more symmetric self-renewing divisions at the expense of asymmetric divisions. Moreover, Lgl1 and hemizygous Ink4a/Arf knockouts in OPC synergistically induce gliomagenesis. Time lapse and total internal reflection microscopy reveals a critical role for Lgl1 in NG2 endocytic routing and links aberrant NG2 recycling to failed differentiation. These data establish Lgl1 as a suppressor of gliomagenesis and positive regulator of asymmetric division and differentiation in the healthy and demyelinated murine brain.

Background

Personal care products may contain many chemicals, some of which are suspected endocrine disrupters. This is an important source of chemical exposure for women, but little is known about how chemical exposure differs among different races/ethnicities.

Objective

This study examines differences in personal care product use among Black, Latina, Vietnamese, Mixed Race, and White women in California.

Methods

We used a community-based participatory process to create and administer a personal care product usage survey to 321 Black, Latina, Vietnamese, Mixed Race, and White women. We used multivariate regression models with pairwise comparisons to examine the frequency of product use by race/ethnicity.

Results

We found distinct trends of personal care product use by race/ethnicity: Latina women typically used makeup most frequently; Black women used certain hair products or styles most frequently; and Vietnamese women were most likely to use facial cleansing products compared to other races/ethnicities. Latina and Vietnamese women were less likely to try to avoid certain ingredients in their products.

Significance

These findings can help estimate disparities in chemical exposure from personal care product use and complement future research on health inequities due to chemical exposures in the larger environmental and social context.

Phagocytosis is required for a broad range of physiological functions, from pathogen defense to tissue homeostasis, but the mechanisms required for phagocytosis of diverse substrates remain incompletely understood. Here, we developed a rapid magnet-based phenotypic screening strategy, and performed eight genome-wide CRISPR screens in human cells to identify genes regulating phagocytosis of distinct substrates. After validating select hits in focused miniscreens, orthogonal assays and primary human macrophages, we show that (1) the previously uncharacterized gene NHLRC2 is a central player in phagocytosis, regulating RhoA-Rac1 signaling cascades that control actin polymerization and filopodia formation, (2) very-long-chain fatty acids are essential for efficient phagocytosis of certain substrates and (3) the previously uncharacterized Alzheimer's disease-associated gene TM2D3 can preferentially influence uptake of amyloid-β aggregates. These findings illuminate new regulators and core principles of phagocytosis, and more generally establish an efficient method for unbiased identification of cellular uptake mechanisms across diverse physiological and pathological contexts.

Phagocytosis is required for a broad range of physiological functions, from pathogen defense to tissue homeostasis, but the mechanisms required for phagocytosis of diverse substrates remain incompletely understood. Here, we developed a rapid magnet-based phenotypic screening strategy, and performed eight genome-wide CRISPR screens in human cells to identify genes regulating phagocytosis of distinct substrates. After validating select hits in focused miniscreens, orthogonal assays and primary human macrophages, we show that (1) the previously uncharacterized gene NHLRC2 is a central player in phagocytosis, regulating RhoA-Rac1 signaling cascades that control actin polymerization and filopodia formation, (2) very-long-chain fatty acids are essential for efficient phagocytosis of certain substrates and (3) the previously uncharacterized Alzheimer's disease-associated gene TM2D3 can preferentially influence uptake of amyloid-β aggregates. These findings illuminate new regulators and core principles of phagocytosis, and more generally establish an efficient method for unbiased identification of cellular uptake mechanisms across diverse physiological and pathological contexts.