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1.
Cell Rep ; 35(12): 109269, 2021 06 22.
Article in English | MEDLINE | ID: mdl-34161768

ABSTRACT

Projection neuron subtype identities in the cerebral cortex are established by expressing pan-cortical and subtype-specific effector genes that execute terminal differentiation programs bestowing neurons with a glutamatergic neuron phenotype and subtype-specific morphology, physiology, and axonal projections. Whether pan-cortical glutamatergic and subtype-specific characteristics are regulated by the same genes or controlled by distinct programs remains largely unknown. Here, we show that FEZF2 functions as a transcriptional repressor, and it regulates subtype-specific identities of both corticothalamic and subcerebral neurons by selectively repressing expression of genes inappropriate for each neuronal subtype. We report that TLE4, specifically expressed in layer 6 corticothalamic neurons, is recruited by FEZF2 to inhibit layer 5 subcerebral neuronal genes. Together with previous studies, our results indicate that a cortical glutamatergic identity is specified by multiple parallel pathways active in progenitor cells, whereas projection neuron subtype-specific identity is achieved through selectively repressing genes associated with alternate identities in differentiating neurons.


Subject(s)
Cerebral Cortex/cytology , DNA-Binding Proteins/metabolism , Nerve Tissue Proteins/metabolism , Neurons/metabolism , Transcription, Genetic , Alleles , Animals , Cell Differentiation/genetics , Electrophysiological Phenomena , Gene Expression Regulation , Mice, Knockout , Mitosis/genetics , Neurons/cytology , Protein Binding , Repressor Proteins/metabolism
2.
Sci Total Environ ; 652: 1022-1029, 2019 Feb 20.
Article in English | MEDLINE | ID: mdl-30380470

ABSTRACT

Personal exposure to pesticides has not been well characterized, especially among adolescents. We used silicone wristbands to assess pesticide exposure in 14 to 16 year old Latina girls (N = 97) living in the agricultural Salinas Valley, California, USA and enrolled in the COSECHA (CHAMACOS of Salinas Examining Chemicals in Homes and Agriculture) Study, a youth participatory action study in an agricultural region of California. We determined pesticide concentrations (ng/g/day) in silicone wristbands worn for one week using gas chromatography electron capture detection and employed gas chromatography mass spectrometry to determine the presence or absence of over 1500 chemicals. Predictors of pesticide detections and concentrations were identified using logistic regression, Wilcoxon rank sum tests, and Tobit regression models. The most frequently detected pesticides in wristbands were fipronil sulfide (87%), cypermethrin (56%), dichlorodiphenyldichloroethylene (DDE) (56%), dacthal (53%), and trans-permethrin (52%). Living within 100 m of active agricultural fields, having carpeting in the home, and having an exterminator treat the home in the past six months were associated with higher odds of detecting certain pesticides. Permethrin concentrations were lower for participants who cleaned their homes daily (GM: 1.9 vs. 6.8 ng/g/day, p = 0.01). In multivariable regression models, participants with doormats in the entryway of their home had lower concentrations (p < 0.05) of cypermethrin (87%), permethrin (99%), fipronil sulfide (69%) and DDE (75%). The results suggest that both nearby agricultural pesticide use and individual behaviors are associated with pesticide exposures.


Subject(s)
Air Pollutants, Occupational/analysis , Environmental Monitoring/instrumentation , Occupational Exposure/analysis , Pesticides/analysis , Adolescent , Agriculture , California/ethnology , Environmental Exposure/analysis , Farmers , Female , Hispanic or Latino , Humans , Silicones
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