Biology subjects

Suzuki, I.

Publications and source records attributed to Suzuki, I..

4 recordsLinked to original sources

bioRxiv2020

Subcellular mRNA localization and local translation of Arhgap11a in radial glial cells regulates cortical development

mRNA localization and local translation enable exquisite spatial and temporal control of gene expression, particularly in highly polarized and elongated cells. These features are especially prominent in radial glial cells (RGCs), which serve as neural and glial precursors of the developing cerebral cortex, and scaffolds for migrating neurons. Yet the mechanisms by which distinct sub-cellular compartments of RGCs accomplish their diverse functions are poorly understood. Here, we demonstrate that subcellular RNA localization and translation of the RhoGAP Arhgap11a controls RGC morphology and mediates cortical cytoarchitecture. Arhgap11a mRNA and protein exhibit conserved localization to RGC basal structures in mice and humans, conferred by a 5'UTR cis-element. Proper RGC morphology relies upon active Arhgap11a mRNA transport and localization to basal structures, where ARHGAP11A is locally synthesized. Thus, RhoA activity is spatially and acutely activated via local translation in RGCs to promote neuron positioning and cortical cytoarchitecture. Altogether, our study demonstrates that mRNA localization and local translation mediate compartmentalization of neural progenitor functions to control brain development. HighlightsO_LIArhgap11a in radial glia non-cell autonomously promotes neuronal migration and lamination C_LIO_LIArhgap11a mRNA localizes to radial glial endfeet via a 5 UTR cis element C_LIO_LIARHGAP11A expression in basal process and endfeet depends upon its localized mRNA C_LIO_LILocalized mRNA and RhoA-GAP activity in endfeet control radial glial morphology C_LI

neuroscience↗

bioRxiv2020

CROCCP2 acts as a human-specific modifier of cilia dynamics and mTOR signalling to promote expansion of cortical progenitors.

The primary cilum is a central component of signalling during neural development, from regional patterning to neuronal differentiation. Here we focus on CROCCP2, a hominid-specific gene duplicate from CROCC (Ciliary Rootlet Coiled Coil), also known as rootletin, that encodes the major protein component of the ciliary rootlet. We find that CROCCP2 is highly expressed in the human fetal brain and not in other primate species. CROCCP2 gain of function in the mouse embryonic cortex results in decreased ciliogenesis, increased mTOR signalling, and increased cell size of radial glial cells, leading to increased generation of intermediate/basal progenitors and increased neuronal output. CROCCP2 impacts cilia dynamics and neurogenesis by inhibition of the IFT20 ciliary trafficking protein. Our data identify a human-specific protein that drives cortical basal progenitor expansion through modulation of ciliary dynamics.

neuroscience↗

bioRxiv2020

Versatile live-cell activity analysis platform for characterization of neuronal dynamics at single-cell and network level

Chronic imaging of neuronal networks in vitro has provided fundamental insights into mechanisms underlying neuronal function. Existing labeling and optical imaging methods, however, cannot be used for continuous and long-term recordings of the dynamics and evolution of neuronal networks, as fluorescence indicators can cause phototoxicity. Here, we introduce a versatile platform for label-free, comprehensive and detailed electrophysiological live-cell imaging of various neurogenic cells and tissues over extended times. We report on a novel dual-mode high-density microelectrode array, which can simultaneously record in i) full-frame mode with 19,584 recording sites and ii) high-signal-to-noise mode with 246 channels. We set out to demonstrate the capabilities of this platform with recordings from primary and iPSC-derived neuronal cultures and tissue preparations over several weeks, providing detailed morpho-electrical phenotypic parameters at subcellular, cellular and network level. Moreover, we developed reliable analysis tools with drastically increased throughput for extracting axonal morphology and conduction parameters.

neuroscience↗

bioRxiv2020

Plastidic Δ6 Fatty-Acid Desaturases With Distinctive Substrate Specificity Regulate The Pool Of C18-PUFAs In The Ancestral Picoalga Ostreococcus tauri

Eukaryotic {Delta}6-desaturases are microsomal enzymes which balance the synthesis of {omega}-3 and {omega}-6 C18-polyunsaturated-fatty-acids (PUFA) accordingly to their specificity. In several microalgae, including O. tauri, plastidic C18-PUFA are specifically regulated by environmental cues suggesting an autonomous control of {Delta}6-desaturation of plastidic PUFA. Sequence retrieval from O. tauri desaturases, highlighted two putative {Delta}6/{Delta}8-desaturases sequences clustering, with other microalgal homologs, apart from other characterized {Delta}-6 desaturases. Their overexpression in heterologous hosts, including N. benthamiana and Synechocystis, unveiled their {Delta}6-desaturation activity and plastid localization. O. tauri lines overexpressing these {Delta}6-desaturases no longer adjusted their plastidic C18-PUFA amount under phosphate starvation but didnt show any obvious physiological alterations. Detailed lipid analyses from the various overexpressing hosts, unravelled that the substrate features involved in the {Delta}6-desaturase specificity importantly involved the lipid head-group and likely the non-substrate acyl-chain, in addition to the overall preference for the {omega}-class of the substrate acyl-chain. The most active desaturase displayed a broad range substrate specificity for plastidic lipids and a preference for {omega}-3 substrates, while the other was selective for {omega}-6 substrates, phosphatidylglycerol and 16:4-galactolipid species specific to the native host. The distribution of plastidial {Delta}6-desaturase products in eukaryotic hosts suggested the occurrence of C18-PUFA export from the plastid. One sentence summaryOsteococcus tauri plastidic lipid C18-PUFA remodelling involves two plastid-located cytochrome-b5 fused {Delta}6-desaturases with distinct preferences for both head-group and acyl-chain.

biochemistry↗