Neuropilin 2 Signaling Is Involved in Cell Positioning of Adult-born Neurons through Glycogen Synthase Kinase-3β (GSK3β)

Ng, Teclise; Hor, Catherine Hong Huan; Chew, Benjamin; Zhao, Jing; Zhong, Zhong; Ryu, Jae Ryun; Goh, Eyleen L. K.

doi:10.1074/jbc.m116.755215

Cited by 19 publications

(16 citation statements)

References 41 publications

(54 reference statements)

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“…GDNF signaling via GFRalpha1 was shown to promote www.nature.com/scientificreports/ the differentiation of ventral precursor cells into GABAergic neurons, enhancing their neuronal morphology and motility 31 . A study by Ng et al points to a new role for NRP2 in the positioning of neurons during adult hippocampal neurogenesis 32 . POU4F1 (also known as BRN3A) knockout mice show a loss of neurons in the trigeminal ganglia, the medial habenula, the red nucleus, and the caudal region of the inferior olivary nucleus but not in the retina and dorsal root ganglia 33 .…”

Section: Discussionmentioning

confidence: 99%

Hypoxia-inducible factor-2α is crucial for proper brain development

Kleszka

Leu

Quinting

et al. 2020

Sci Rep

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Sufficient tissue oxygenation is required for regular brain function; thus oxygen supply must be tightly regulated to avoid hypoxia and irreversible cell damage. If hypoxia occurs the transcription factor complex hypoxia-inducible factor (HIF) will accumulate and coordinate adaptation of cells to hypoxia. However, even under atmospheric O2 conditions stabilized HIF-2α protein was found in brains of adult mice. Mice with a neuro-specific knockout of Hif-2α showed a reduction of pyramidal neurons in the retrosplenial cortex (RSC), a brain region responsible for a range of cognitive functions, including memory and navigation. Accordingly, behavioral studies showed disturbed cognitive abilities in these mice. In search of the underlying mechanisms for the specific loss of pyramidal cells in the RSC, we found deficits in migration in neural stem cells from Hif-2α knockout mice due to altered expression patterns of genes highly associated with neuronal migration and positioning.

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Section: Discussionmentioning

confidence: 99%

Hypoxia-inducible factor-2α is crucial for proper brain development

Kleszka

Leu

Quinting

et al. 2020

Sci Rep

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“…IGF1 regulates known factors of neuronal migration including GSK3B, PSA-NCAM, Cdk5 and reelin [12,44,82]. Signalling studies have revealed that inhibiting the activity of GSK3B, a protein inactivated downstream of IGF1 signalling, is sufficient to increase the number of adult-born neurons localized to the oGCL [83]. This may be an indication that IGF1 can accelerate development of newborn neurons following trauma.…”

Section: Migrationmentioning

confidence: 99%

Insulin-like growth factor-1 overexpression increases long-term survival of posttrauma-born hippocampal neurons while inhibiting ectopic migration following traumatic brain injury

Littlejohn

Scott

Saatman

2020

acta neuropathol commun

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Cellular damage associated with traumatic brain injury (TBI) manifests in motor and cognitive dysfunction following injury. Experimental models of TBI reveal cell death in the granule cell layer (GCL) of the hippocampal dentate gyrus acutely after injury. Adult-born neurons residing in the neurogenic niche of the GCL, the subgranular zone, are particularly vulnerable. Injury-induced proliferation of neural progenitors in the subgranular zone supports recovery of the immature neuron population, but their development and localization may be altered, potentially affecting long-term survival. Here we show that increasing hippocampal levels of insulin-like growth factor-1 (IGF1) is sufficient to promote end-stage maturity of posttrauma-born neurons and improve cognition following TBI. Mice with conditional overexpression of astrocyte-specific IGF1 and wild-type mice received controlled cortical impact or sham injury and bromo-2′-deoxyuridine injections for 7d after injury to label proliferating cells. IGF1 overexpression increased the number of GCL neurons born acutely after trauma that survived 6 weeks to maturity (NeuN+BrdU+), and enhanced their outward migration into the GCL while significantly reducing the proportion localized ectopically to the hilus and molecular layer. IGF1 selectively affected neurons, without increasing the persistence of posttrauma-proliferated glia in the dentate gyrus. IGF1 overexpressing animals performed better during radial arm water maze reversal testing, a neurogenesis-dependent cognitive test. These findings demonstrate the ability of IGF1 to promote the long-term survival and appropriate localization of granule neurons born acutely after a TBI, and suggest these new neurons contribute to improved cognitive function.

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“…However, the role of Sema 3F–NRP2 signaling in the development of hippocampal and cortical GABAergic circuitry has been less well characterized. NRP2 signaling is involved in cell positioning of adult-born neurons through regulation of glycogen synthase kinase-3 [36]. NRP2 expression in precursors located in the ventral ventricular zone as well as tangentially migrating GABA+ interneurons is noted when these neurons enter the cortical plate [19, 21, 37].…”

Section: Introductionmentioning

confidence: 99%

Deletion of Semaphorin 3F in Interneurons Is Associated with Decreased GABAergic Neurons, Autism-like Behavior, and Increased Oxidative Stress Cascades

Jagadapillai

Gozal

et al. 2019

Mol Neurobiol

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Autism and epilepsy are diseases which have complex genetic inheritance. Genome-wide association and other genetic studies have implicated at least 500+ genes associated with the occurrence of autism spectrum disorders (ASD) including the human semaphorin 3F (Sema 3F) and neuropilin 2 (NRP2) genes. However, the genetic basis of the comorbid occurrence of autism and epilepsy is unknown. The aberrant development of GABAergic circuitry is a possible risk factor in autism and epilepsy. Molecular biological approaches were used to test the hypothesis that cell-specific genetic variation in mouse homologs affects the formation and function of GABAergic circuitry. The empirical analysis with mice homozygous null for one of these genes, Sema 3F, in GABAergic neurons substantiated these predictions. Notably, deletion of Sema 3F in interneurons but not excitatory neurons during early development decreased the number of interneurons/neurites and mRNAs for cell-specific GABAergic markers and increased epileptogenesis and autistic behaviors. Studies of interneuron cell-specific knockout of Sema 3F signaling suggest that deficient Sema 3F signaling may lead to neuroinflammation and oxidative stress. Further studies of mouse KO models of ASD genes such as Sema 3F or NRP2 may be informative to clinical phenotypes contributing to the pathogenesis in autism and epilepsy patients.

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Neuropilin 2 Signaling Is Involved in Cell Positioning of Adult-born Neurons through Glycogen Synthase Kinase-3β (GSK3β)

Cited by 19 publications

References 41 publications

Hypoxia-inducible factor-2α is crucial for proper brain development

Hypoxia-inducible factor-2α is crucial for proper brain development

Insulin-like growth factor-1 overexpression increases long-term survival of posttrauma-born hippocampal neurons while inhibiting ectopic migration following traumatic brain injury

Deletion of Semaphorin 3F in Interneurons Is Associated with Decreased GABAergic Neurons, Autism-like Behavior, and Increased Oxidative Stress Cascades

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