Molecular insights into fetal alcohol syndrome : A cerebral cortex perspective

Abstract

Maternal alcohol consumption during pregnancy can trigger a wide range of developmental, neurobehavioral, neurobiological, and physiological impairments. The spectrum of alcohol’s teratogenic diseases is known as fetal alcohol spectrum disorder (FASD). Among the different mechanisms impacted on the central nervous system (CNS), one of the most important abnormalities appears to be neuronal cell migration. Furthermore, one of the migration processes impacted is the multipolar to bipolar step of the inside out neuronal migration.

During my master thesis, we studied the consequences of alcohol upon its prenatal exposure in the somatosensory cortex, especially migrating neurons. The maternal alcohol consumption was emulated with the “drinking in the dark” mouse paradigm. Single-cell RNA sequencing (scRNA-seq) was used to analyze the somatosensory cortex of E17 mouse embryo exposed to alcohol during pregnancy.

A scRNA-seq analysis pipeline adjusted especially for this experiment showed the presence of 11 cell populations: interneurons, pericytes, endothelial cells, microglia, apical and intermediate progenitors, astrocytes, oligodendrocytes progenitors cells, cajal retzius cells, newborn projection migrating neurons and cortical projection neurons. Alcohol did not impact the proportion and the fate of the cells. Differentially expressed genes were found and used to study enriched pathways and regulation networks. This resulted in pathways’ discovery such as genes involved in the regionalization of the brain.