Biology subjects

Paez-Beltran, L. E.

Publications and source records attributed to Paez-Beltran, L. E..

3 recordsLinked to original sources

bioRxiv2026

Third Trimester-Equivalent Alcohol Exposure Induces Sex-Dependent Alterations in Locomotor Activity, Anxiety-Risky Behaviors, and Enhances Mechanical Allodynia in Adulthood

Prenatal alcohol exposure (PAE) causes fetal alcohol spectrum disorders (FASDs), which are neurodevelopmental conditions characterized by behavioral dysregulation, learning deficits, and cognitive inflexibilities. Alcohol exposure is harmful at all stages of human gestation, including the third trimester. This developmental window--characterized by rapid brain growth, myelination, and neural circuit formation--may be particularly vulnerable, yet the long-lasting behavioral and sensory consequences of exposure during this period remain poorly understood. In this study, neonatal mouse pups were exposed to ethanol (EtOH) or air vapor from postnatal day (P) 4 to P8, which is equivalent to a third-trimester alcohol exposure (TTAE) in humans. Blood ethanol concentrations measured at P8 reached approximately 250 mg/dL, consistent with binge-level exposure. Air- and EtOH-exposed mice were then assessed as adults at 5-6 months of age for locomotor activity, anxiety-related risky behaviors, recognition memory, and increased susceptibility to peripheral neuropathy, as indicated by sensitization to light touch following minor chronic constriction injury (mCCI) of the sciatic nerve. We found that TTAE was sufficient to produce long-lasting behavioral outcomes in a sex-dependent manner. Notably, EtOH-exposed males exhibited increased spontaneous locomotor activity and risky behavior, whereas EtOH-exposed females showed minimal or decreased changes compared to their respective controls. However, both EtOH-exposed male and female mice exhibited marked increases in light-touch sensitization, referred to as mechanical allodynia, following mCCI, a response absent in air-exposed controls. Together, these findings reveal that TTAE is highly detrimental to behavioral regulation and creates a vulnerability to developing neuropathic pain in adulthood.

neuroscience↗

bioRxiv2026

ASCL1 and OLIG2 Expression Dynamics Control Glial Cell Fate and Regional Diversity in the Dorsal Forebrain

Gliogenesis is a multistep process that begins with the specification of glial progenitors (GPs) into migrating and proliferating precursor cells, which later differentiate into mature astrocytes and oligodendrocytes. How these developmental processes are coordinated to generate the diverse glial lineages in gray matter (GM) and white matter (WM) in the brain remains poorly understood. Here, we show that the basic-helix-loop-helix (bHLH) transcription factor ASCL1 serves as a direct mechanistic link between glial cell fate specification, migration, proliferation, and differentiation in the dorsal forebrain. Notably, ASCL1 is dynamically expressed in GPs, initiating in the ventricular zone (VZ), peaking in the intermediate zone (IZ), but is downregulated once GPs enter the cortical plate. Lineage tracing of ASCL1+ GPs demonstrates that they subsequently co-express OLIG2 to generate both astrocytes and oligodendrocytes in an "outside-in" pattern starting from the upper cortex inward to the corpus callosum, the opposite pattern of neurogenesis. Gain- and loss-of-function experiments further reveal that a sustained ASCL1 expression is essential for inducing sufficient levels of OLIG2 required to specify oligodendrocyte precursor cell (OPC) fate. Interestingly, a persistent ASCL1 expression also maintains OPCs into postnatal stages by promoting their self-renewal while suppressing their differentiation into postmitotic oligodendrocytes. Together, these findings establish ASCL1 as a key regulator of the spatiotemporal order of glial lineage diversity in cortical GM and callosal WM and implicate ASCL1 dysregulation as an underlying mechanism in the pathogenesis of gliomas.

neuroscience↗

bioRxiv2023

Glioblastoma initiation, migration, and cell types are regulated by core bHLH transcription factors ASCL1 and OLIG2

Glioblastomas (GBMs) are highly aggressive, infiltrative, and heterogeneous brain tumors driven by complex driver mutations and glioma stem cells (GSCs). The neurodevelopmental transcription factors ASCL1 and OLIG2 are co-expressed in GBMs, but their role in regulating the heterogeneity and hierarchy of GBM tumor cells is unclear. Here, we show that oncogenic driver mutations lead to dysregulation of ASCL1 and OLIG2, which function redundantly to initiate brain tumor formation in a mouse model of GBM. Subsequently, the dynamic levels and reciprocal binding of ASCL1 and OLIG2 to each other and to downstream target genes then determine the cell types and degree of migration of tumor cells. Single-cell RNA sequencing (scRNA-seq) reveals that a high level of ASCL1 is key in defining GSCs by upregulating a collection of ribosomal protein, mitochondrial, neural stem cell (NSC), and cancer metastasis genes - all essential for sustaining the high proliferation, migration, and therapeutic resistance of GSCs.

neuroscience↗