RESUMO
Maternal well-being is important for the development of the fetus, with a key influence on its nervous system. In this issue of Neuron, Krontira et al.1 implicate glucocorticoids, the stress hormones, in the regulation of neural stem cell identity and proliferation, with long-lasting consequences on brain architecture and educational attainment.
Assuntos
Glucocorticoides , Neurogênese , Humanos , Glucocorticoides/farmacologia , Neurogênese/efeitos dos fármacos , Neurogênese/fisiologia , Neurônios/efeitos dos fármacos , Neurônios/fisiologia , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/citologia , Células-Tronco Neurais/efeitos dos fármacosRESUMO
Folding of the cerebral cortex is a key aspect of mammalian brain development and evolution, and defects are linked to severe neurological disorders. Primary folding occurs in highly stereotyped patterns that are predefined in the cortical germinal zones by a transcriptomic protomap. The gene regulatory landscape governing the emergence of this folding protomap remains unknown. We characterized the spatiotemporal dynamics of gene expression and active epigenetic landscape (H3K27ac) across prospective folds and fissures in ferret. Our results show that the transcriptomic protomap begins to emerge at early embryonic stages, and it involves cell-fate signaling pathways. The H3K27ac landscape reveals developmental cell-fate restriction and engages known developmental regulators, including the transcription factor Cux2. Manipulating Cux2 expression in cortical progenitors changed their proliferation and the folding pattern in ferret, caused by selective transcriptional changes as revealed by single-cell RNA sequencing analyses. Our findings highlight the key relevance of epigenetic mechanisms in defining the patterns of cerebral cortex folding.
Assuntos
Córtex Cerebral , Epigênese Genética , Furões , Regulação da Expressão Gênica no Desenvolvimento , Animais , Córtex Cerebral/metabolismo , Córtex Cerebral/embriologia , Furões/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Transcriptoma , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Histonas/metabolismo , Histonas/genética , Redes Reguladoras de GenesRESUMO
Cortical neurogenesis follows a simple lineage: apical radial glia cells (RGCs) generate basal progenitors, and these produce neurons. How this occurs in species with expanded germinal zones and a folded cortex, such as human, remains unclear. We used single-cell RNA sequencing from individual cortical germinal zones in ferret and barcoded lineage tracking to determine the molecular diversity of progenitor cells and their lineages. We identified multiple RGC classes that initiate parallel lineages, converging onto a common class of newborn neuron. Parallel RGC classes and transcriptomic trajectories were repeated across germinal zones and conserved in ferret and human, but not in mouse. Neurons followed parallel differentiation trajectories in the gyrus and sulcus, with different expressions of human cortical malformation genes. Progenitor cell lineage multiplicity is conserved in the folded mammalian cerebral cortex.