The expression and roles of Nde1 and Ndel1 in the adult mammalian central nervous system

Pei, Zhenglei; Lang, Bradley T.; Fragoso, Yára Dadalti; Shearer, Kirsty; Zhao, Lu; McCaffery, Peter; Shen, Sanbing; Ding, Yu; McCaig, Colin; Collinson, J. Martin

doi:10.1016/j.neuroscience.2014.04.031

Cited by 16 publications

(13 citation statements)

References 42 publications

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“…Further, in the mature nervous system, the recent work of Pei et al (2014) characterized an NDEL1 expression pattern similar to the one described here. Along these lines, marked expression of NDEL1 was observed in cortex and cerebellar cell populations, whereas fairly modest expression was detected within the principal cell layers of the hippocampus.…”

Section: Discussionsupporting

confidence: 75%

Status epilepticus stimulates NDEL1 expression via the CREB/CRE pathway in the adult mouse brain

et al. 2016

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Nuclear distribution element-like 1 (NDEL1/NUDEL) is a mammalian homolog of the Aspergillus nidulans nuclear distribution molecule NudE. NDEL1 plays a critical role in neuronal migration, neurite outgrowth and neuronal positioning during brain development; however within the adult central nervous system, limited information is available regarding NDEL1 expression and functions. Here, the goal was to examine inducible NDEL1 expression in the adult mouse forebrain. Immunolabeling revealed NDEL1 within the forebrain, including the cortex and hippocampus, as well as the midbrain and hypothalamus. Expression was principally localized to perikarya. Using a combination of immunolabeling and RNA seq profiling, we detected a marked and long-lasting upregulation of NDEL1 expression within the hippocampus following a pilocarpine-evoked repetitive seizure paradigm. Chromatin immunoprecipitation (ChIP) analysis identified a cAMP response element-binding protein (CREB) binding site within the CpG island proximal to the NDEL1 gene, and in vivo transgenic repression of CREB led to a marked downregulation of seizure-evoked NDEL1 expression. Together these data indicate that NDEL1 is inducibly expressed in the adult nervous system, and that signaling via the CREB/CRE transcriptional pathway is likely involved. The role of NDEL1 in neuronal migration and neurite outgrowth during development raises the interesting prospect that inducible NDEL1 in the mature nervous system could contribute to the well-characterized structural and functional plasticity resulting from repetitive seizure activity.

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Section: Discussionsupporting

confidence: 75%

Status epilepticus stimulates NDEL1 expression via the CREB/CRE pathway in the adult mouse brain

et al. 2016

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“…The EB-binding site on ankyrin G is unknown, but the tail domain of the 480-kDa ankyrin G notably contains six EB-binding SxIP motifs, making it a strong candidate for EB binding (Jiang et al, 2012). It is likely that several other microtubule-associated proteins have a specific role at the AIS: nuclear distribution element-like 1 (Ndel1/Nudel), a cytoskeleton regulator, concentrates at the AIS (Bradshaw et al, 2008;2011;Pei et al, 2014;Sasaki et al, 2000). Antibodies against phosphorylated IkBa label a microtubule-associated epitope along the AIS (Sanchez-Ponce, Tapia, Muñoz, & Garrido, 2008;Schultz et al, 2006), but the target is not IkBa itself (Buffington, Sobotzik, Schultz, & Rasband, 2012).…”

Section: The Ais Molecular Components and Their Interactions 31 The mentioning

confidence: 99%

The Axon Initial Segment, 50Years Later

Leterrier

2016

Current Topics in Membranes

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The axon initial segment is a highly specialized neuronal compartment, identified almost 50years ago by the pioneers of electron microscopy. Located in the first 50μm of the axon, it contains unique cytoskeletal features and concentrates a repertoire of specific scaffold and membrane proteins that assembles just after axon determination. The axon initial segment (AIS) supports two crucial physiological functions of the mature neuron: first, it generates and shapes the action potential. Second, it separates the cell body from the axon, preserving the molecular identity of each compartment. In addition to a diffusion barrier restricting membrane proteins and lipids exchange, an intracellular filter has been proposed that could selectively exclude somatodendritic vesicles and recruit axonal cargoes. Finally, the AIS scaffold is capable of morphological plasticity during development or in response to network activity. These changes directly impact the neuron excitability, allowing an adaptive and homeostatic response. These plastic electrogenic properties, as well as the regulation of protein transport to and from the axon, may have important implications in several neuropathological contexts where the AIS structure is altered. Fifty years after its first characterization, the AIS thus emerges as a nexus for both neuronal organization and physiology.

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“…Ndel1 plays multiple roles in neurodevelopmental processes (Woo et al, 2019). Ndel1 is broadly expressed in the brain, including in the majority of cortical neurons (Pei et al, 2014). Ndel1 de ciency results in neuronal migration defects, fragmented microtubules, dendritic/synaptic pathologies, and early embryonic lethality (Jiang et al, 2016;Sasaki et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

Expression and function of Ndel1 during the differentiation of neural stem cells induced by hippocampal exosomes

Wang

et al. 2020

Preprint

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BackgroundIn the brain of adult mammals, neural stem cells persist in the subventricular zone of the lateral ventricle and the subgranular zone of the dentate gyrus, which are specialized niches with proliferative capacity. Most neural stem cells are in a quiescent state, but in response to extrinsic stimuli, they can exit from quiescence and become reactivated to produce new neurons, so neural stem cells are considered to be a potential source for cell replacement therapy of many nervous system diseases. We characterized the expression of Ndel1 during the differentiation of neural stem cells induced by hippocampus exosomes, and assessed the effect of Ndel1 on neural stem cells differentiationMethodsHippocampal exosomes were isolated and extracted, and co-cultured exosomes with neural stem cells. Western blot, flow cytometry, and immunofluorescence analyses were used to analyze expression of neuronal markers. Further, utilizing high-throughput RNA sequencing technology, we found that nudE neurodevelopment protein 1-like 1 was significantly up-regulated in exosomes derived from denervated hippocampus, and then characterized its mechanism and function during neural stem cells differentiation by qRT-PCR, western blot, flow cytometry, and immunofluorescence analyses.ResultsOur results revealed that exosomes of denervated hippocampus promoted the differentiation of neural stem cells into neuron. Hence, we identified that nudE neurodevelopment protein 1-like 1 (Ndel1) was significantly up-regulated and highly expressed in the nervous system. In addition, we found that miR-107-3p may regulate NSCs differentiation by targeting Ndel1.ConclusionsOur results revealed that deafferentation of the hippocampal exosomes co-cultured with NSCs could promote them to differentiate into neurons. Hence, we found that miR-107-3p may regulate NSCs differentiation by targeting Ndel1. Importantly, Ndel1 enhanced spatial learning and hippocampal neurogenesis in rats after FF transection In vivo. These findings set the stage for a better understanding of neurogenesis, a process that one day may inspire new treatments for central nervous system diseases.

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The expression and roles of Nde1 and Ndel1 in the adult mammalian central nervous system

Abstract: Graphical abstractNde1 (red) is localised to the GFAP-positive (green) stem cell of the subventricular zone of the lateral ventricle, and its overexpression in neural stem cells promotes neuronal differentiation while inhibiting astroglial differentiation.

Cited by 16 publications

References 42 publications

Status epilepticus stimulates NDEL1 expression via the CREB/CRE pathway in the adult mouse brain

Status epilepticus stimulates NDEL1 expression via the CREB/CRE pathway in the adult mouse brain

The Axon Initial Segment, 50Years Later

Expression and function of Ndel1 during the differentiation of neural stem cells induced by hippocampal exosomes

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