CRMP1 and CRMP4 are required for proper orientation of dendrites of cerebral pyramidal neurons in the developing mouse brain

Takaya, Ryosuke; Nagai, Jun; Piao, Wenfui; Niisato, Emi; Nakabayashi, Takeru; Yamazaki, Yuki; Nakamura, Fumio; Yamashita, Naoya; Kolattukudy, P.E.; Goshima, Yoshio; Ohshima, Toshio

doi:10.1016/j.brainres.2016.11.003

Cited by 12 publications

(10 citation statements)

References 27 publications

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“…The CRMP1-5 family of proteins form heterotetramers and CRMP2 is the most prevalent family member (Goshima et al, 1995;Strittmatter, 1996, 1997;Deo et al, 2004;Schmidt and Strittmatter, 2007). The CRMP family titrates axonal growth in multiple situations (Goshima et al, 1995;Arimura et al, 2005;Niisato et al, 2012Niisato et al, , 2013Khazaei et al, 2014;Nagai et al, 2015Nagai et al, , 2016Takaya et al, 2017). Previous studies have suggested an involvement of CRMPs in myelin ligand signaling.…”

Section: Discussionmentioning

confidence: 99%

Plexina2 and CRMP2 Signaling Complex Is Activated by Nogo-A-Liganded Ngr1 to Restrict Corticospinal Axon Sprouting after Trauma

et al. 2019

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After brain or spinal cord trauma, interaction of Nogo-A with neuronal NgR1 limits regenerative axonal sprouting and functional recovery. Cellular signaling by lipid-anchored NgR1 requires a coreceptor but the relevant partner in vivo is not clear. Here, we examined proteins enriched in NgR1 immunoprecipitates by Nogo-A exposure, identifying CRMP2, a cytosolic protein implicated in axon growth inhibition by Semaphorin/Plexin complexes. The Nogo-A-induced association of NgR1 with CRMP2 requires PlexinA2 as a coreceptor. Non-neuronal cells expressing both NgR1 and PlexinA2, but not either protein alone, contract upon Nogo-A exposure. Inhibition of cortical axon regeneration by Nogo-A depends on a NgR1/PlexinA2 genetic interaction because double-heterozygous NgR1 ϩ/Ϫ , PlexinA2 ϩ/Ϫ neurons, but not single-heterozygote neurons, are rescued from Nogo-A inhibition. NgR1 and PlexinA2 also interact genetically in vivo to restrict corticospinal sprouting in mouse cervical spinal cord after unilateral pyramidotomy. Greater post-injury sprouting in NgR1 ϩ/Ϫ , PlexinA2 ϩ/Ϫ mice supports enhanced neurological recovery of a mixed female and male double-heterozygous cohort. Thus, a NgR1/PlexinA2/CRMP2 ternary complex limits neural repair after adult mammalian CNS trauma. Significance StatementSeveral decades of molecular research have suggested that developmental regulation of axon growth is distinct in most regards from titration of axonal regenerative growth after adult CNS trauma. Among adult CNS pathways, the oligodendrocyte Nogo-A inhibition of growth through NgR1 is thought to have little molecular relationship to axonal guidance mechanisms active embryonically. Here, biochemical analysis of NgR1 function uncovered a physical complex with CRMP cytoplasmic mediators, and this led to appreciation of a role for PlexinA2 in concert with NgR1 after adult trauma. The data extend molecular understanding of neural repair after CNS trauma and link it to developmental processes.

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Section: Discussionmentioning

confidence: 99%

Plexina2 and CRMP2 Signaling Complex Is Activated by Nogo-A-Liganded Ngr1 to Restrict Corticospinal Axon Sprouting after Trauma

et al. 2019

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“…These genes may be interesting candidates or contribute to identify new factors to enhance MEF lineage-reprogramming into iNs. Collapsin Response Mediator Protein 1 (Crmp1) is part of CRMP family of proteins and is typically associated as mediator of sema3A signaling and axon guidance [16] [17]. Interestingly, some CRMP proteins are diferentially expressed in axon and dendrites of distinct neuronal types [16].…”

Section: Resultsmentioning

confidence: 99%

Transcriptional profile of induced and primary neurons reveals new candidate genes for lineage reprogramming

Marques‐Coelho

Souza²,

Costa

2017

Matters

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“…In addition to several tubulin genes, four of the five Crmp genes were up-regulated in TCDD-exposed hippocampi. CRMP proteins can positively and negatively regulate microtubule polymerization dynamics through interaction with tubulins, allowing them to regulate neurite outgrowth (Fukata et al 2002;Uchida et al 2005;Yoshimura et al 2005;Aylsworth et al 2009;Brot et al 2010;Takaya et al 2017;Ji et al 2018). In addition, many of the genes involved in the axon guidance have been described to have vital roles in regulation of dendritic arborization (Ledda and Paratcha 2017).…”

Section: Transcriptional Outcomes Of Gestational Low-dose Tcdd Exposurementioning

confidence: 99%

Effects of Low-Dose Gestational TCDD Exposure on Behavior and on Hippocampal Neuron Morphology and Gene Expression in Mice

Gileadi

Swamy

Hore

et al. 2021

Environ Health Perspect

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BACKGROUND: 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a persistent and toxic environmental pollutant. Gestational exposure to TCDD has been linked to cognitive and motor deficits, and increased incidence of autism spectrum disorder (ASD) traits in children. Most animal studies of these neurodevelopmental effects involve acute TCDD exposure, which does not model typical exposure in humans. OBJECTIVES: The aim of the study was to establish a dietary low-dose gestational TCDD exposure protocol and performed an initial characterization of the effects on offspring behavior, neurodevelopmental phenotypes, and gene expression. METHODS: Throughout gestation, pregnant C57BL/6J mice were fed a diet containing a low dose of TCDD (9 ng TCDD/kg body weight per day) or a control diet. The offspring were tested in a battery of behavioral tests, and structural brain alterations were investigated by magnetic resonance imaging. The dendritic morphology of pyramidal neurons in the hippocampal Cornu Ammonis (CA)1 area was analyzed. RNA sequencing was performed on hippocampi of postnatal day 14 TCDD-exposed and control offspring. RESULTS: TCDD-exposed females displayed subtle deficits in motor coordination and reversal learning. Volumetric difference between diet groups were observed in regions of the hippocampal formation, mammillary bodies, and cerebellum, alongside higher dendritic arborization of pyramidal neurons in the hippocampal CA1 region of TCDD-exposed females. RNA-seq analysis identified 405 differentially expressed genes in the hippocampus, enriched for genes with functions in regulation of microtubules, axon guidance, extracellular matrix, and genes regulated by SMAD3. DISCUSSION: Exposure to 9 ng TCDD/kg body weight per day throughout gestation was sufficient to cause specific behavioral and structural brain phenotypes in offspring. Our data suggest that alterations in SMAD3-regulated microtubule polymerization in the developing postnatal hippocampus may lead to an abnormal morphology of neuronal dendrites that persists into adulthood. These findings show that environmental low-dose gestational exposure to TCDD can have significant, long-term impacts on brain development and function.

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CRMP1 and CRMP4 are required for proper orientation of dendrites of cerebral pyramidal neurons in the developing mouse brain

Cited by 12 publications

References 27 publications

Plexina2 and CRMP2 Signaling Complex Is Activated by Nogo-A-Liganded Ngr1 to Restrict Corticospinal Axon Sprouting after Trauma

Plexina2 and CRMP2 Signaling Complex Is Activated by Nogo-A-Liganded Ngr1 to Restrict Corticospinal Axon Sprouting after Trauma

Transcriptional profile of induced and primary neurons reveals new candidate genes for lineage reprogramming

Effects of Low-Dose Gestational TCDD Exposure on Behavior and on Hippocampal Neuron Morphology and Gene Expression in Mice

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