Cell fusion is a fundamental process in the development of multicellular organisms, yet its impact on gene regulation, particularly during crucial developmental stages, remains poorly understood. The epidermis comprises 8-10 syncytial cells, with the largest integrating 139 individual nuclei through cell-cell fusion governed by the fusogenic protein EFF-1. To explore the effects of cell fusion on developmental progression and associated gene expression changes, we conducted transcriptomic analyses of fusion-deficient mutants.
View Article and Find Full Text PDFHistone variants, which can be expressed outside of S-phase and deposited DNA synthesis-independently, provide long-term histone replacement in postmitotic cells, including neurons. Beyond replenishment, histone variants also play active roles in gene regulation by modulating chromatin states or enabling nucleosome turnover. Here, we uncover crucial roles for the histone H3 variant H3.
View Article and Find Full Text PDFLoss-of-function mutations in chromatin remodeler gene are a cause of Coffin-Siris syndrome, a developmental disorder characterized by dysgenesis of corpus callosum. Here, we characterize function during cortical development and find unexpectedly selective roles for in subplate neurons (SPNs). SPNs, strategically positioned at the interface of cortical gray and white matter, orchestrate multiple developmental processes indispensable for neural circuit wiring.
View Article and Find Full Text PDFChromatin regulates spatiotemporal gene expression during neurodevelopment, but it also mediates DNA damage repair essential to proliferating neural progenitor cells (NPCs). Here, we uncover molecularly dissociable roles for nucleosome remodeler Ino80 in chromatin-mediated transcriptional regulation and genome maintenance in corticogenesis. We find that conditional Ino80 deletion from cortical NPCs impairs DNA double-strand break (DSB) repair, triggering p53-dependent apoptosis and microcephaly.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
February 2015
Hibernating mammals possess a unique ability to reduce their body temperature to ambient levels, which can be as low as -2.9 °C, by active down-regulation of metabolism. Despite such a depressed physiologic phenotype, hibernators still maintain activity in their nervous systems, as evidenced by their continued sensitivity to auditory, tactile, and thermal stimulation.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
October 2014
Relying almost exclusively on their acute sense of touch, tactile-foraging birds can feed in murky water, but the cellular mechanism is unknown. Mechanical stimuli activate specialized cutaneous end organs in the bill, innervated by trigeminal afferents. We report that trigeminal ganglia (TG) of domestic and wild tactile-foraging ducks exhibit numerical expansion of large-diameter mechanoreceptive neurons expressing the mechano-gated ion channel Piezo2.
View Article and Find Full Text PDFNeurosci Res
September 2014
The neocortex underlies not only remarkable motor and sensory capabilities, but also some of our most distinctly human cognitive functions. The emergence of these higher functions during evolution was accompanied by structural changes in the neocortex, including the acquisition of areal specializations such as Broca's speech and language area. The study of these evolutionary mechanisms, which likely involve species-dependent gene expression and function, represents a substantial challenge.
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