Developmental Regulation of Microtubule‐Associated Protein 2 Expression in Regions of Mouse Brain

Crandall, James E.; Fischer, Itzhak

doi:10.1111/j.1471-4159.1989.tb09261.x

Cited by 49 publications

(24 citation statements)

References 60 publications

(61 reference statements)

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“…5Db). The level of the low molecular weight form of MAP2 (MAP2c), known to be expressed at early developmental stages but to decrease postnatally after 2 weeks (Crandall and Fischer, 1989), was not different between the genotypes. Moreover, MAP2a/b is largely located in dendrites and axons, whereas MAP2c is widely located in every neuronal compartment (Tucker et al, 1988).…”

Section: Resultsmentioning

confidence: 99%

Deletion of a single allele of thePex11βgene is sufficient to cause oxidative stress, delayed differentiation and neuronal death in mouse brain

Ahlemeyer

Gottwald

Baumgart-Vogt

2012

Disease Models &Amp; Mechanisms

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SUMMARYImpaired neuronal migration and cell death are commonly observed in patients with peroxisomal biogenesis disorders (PBDs), and in mouse models of this diseases. In Pex11β-deficient mice, we observed that the deletion of a single allele of the Pex11β gene (Pex11β+/− heterozygous mice) caused cell death in primary neuronal cultures prepared from the neocortex and cerebellum, although to a lesser extent as compared with the homozygous-null animals (Pex11β−/− mice). In corresponding brain sections, cell death was rare, but differences between the genotypes were similar to those found in vitro. Because PEX11β has been implicated in peroxisomal proliferation, we searched for alterations in peroxisomal abundance in the brain of heterozygous and homozygous Pex11β-null mice compared with wild-type animals. Deletion of one allele of the Pex11β gene slightly increased the abundance of peroxisomes, whereas the deletion of both alleles caused a 30% reduction in peroxisome number. The size of the peroxisomal compartment did not correlate with neuronal death. Similar to cell death, neuronal development was delayed in Pex11β+/− mice, and to a further extent in Pex11β−/− mice, as measured by a reduced mRNA and protein level of synaptophysin and a reduced protein level of the mature isoform of MAP2. Moreover, a gradual increase in oxidative stress was found in brain sections and primary neuronal cultures from wild-type to heterozygous to homozygous Pex11β-deficient mice. SOD2 was upregulated in neurons from Pex11β+/− mice, but not from Pex11β−/− animals, whereas the level of catalase remained unchanged in neurons from Pex11β+/− mice and was reduced in those from Pex11β−/− mice, suggesting a partial compensation of oxidative stress in the heterozygotes, but a failure thereof in the homozygous Pex11β−/− brain. In conclusion, we report the alterations in the brain caused by the deletion of a single allele of the Pex11β gene. Our data might lead to the reconsideration of the clinical treatment of PBDs and the common way of using knockout mouse models for studying autosomal recessive diseases.

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Section: Resultsmentioning

confidence: 99%

Deletion of a single allele of thePex11βgene is sufficient to cause oxidative stress, delayed differentiation and neuronal death in mouse brain

Ahlemeyer

Gottwald

Baumgart-Vogt

2012

Disease Models &Amp; Mechanisms

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“…The best-studied neuronal MAPs are Map2, Map1b and Tau. These proteins exist as several isoforms that are produced by alternative splicing, and their expression is developmentally regulated [46]–[49]. The function of Map2 and Tau are thought to be, at least in part, functionally redundant with Map1b during the early brain development.…”

Section: Discussionmentioning

confidence: 99%

Dab2ip Regulates Neuronal Migration and Neurite Outgrowth in the Developing Neocortex

et al. 2012

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Dab2ip (DOC-2/DAB2 interacting protein) is a member of the Ras GTPase-activating protein (GAP) family that has been previously shown to function as a tumor suppressor in several systems. Dab2ip is also highly expressed in the brain where it interacts with Dab1, a key mediator of the Reelin pathway that controls several aspects of brain development and function. We found that Dab2ip is highly expressed in the developing cerebral cortex, but that mutations in the Reelin signaling pathway do not affect its expression. To determine whether Dab2ip plays a role in brain development, we knocked down or over expressed it in neuronal progenitor cells of the embryonic mouse neocortex using in utero electroporation. Dab2ip down-regulation severely disrupts neuronal migration, affecting preferentially late-born principal cortical neurons. Dab2ip overexpression also leads to migration defects. Structure-function experiments in vivo further show that both PH and GRD domains of Dab2ip are important for neuronal migration. A detailed analysis of transfected neurons reveals that Dab2ip down- or up-regulation disrupts the transition from a multipolar to a bipolar neuronal morphology in the intermediate zone. Knock down of Dab2ip in neurons ex-vivo indicates that this protein is necessary for proper neurite development and for the expression of several major neuronal microtubule associated proteins (MAPs), which are important for neurite growth and stabilization. Thus, our study identifies, for the first time, a critical role for Dab2ip in mammalian cortical development and begins to reveal molecular mechanisms that underlie this function.

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“…Some immunofluorescence images were processed using PHOTOSHOP (Adobe Systems, Mountain View, CA). Other antibodies used were anti-MAP2 against microtubuleassociated protein 2 (24) and H014 (an axonal marker) recognizing highly phosphorylated neurofilament protein NF(M) (25).…”

Section: Methodsmentioning

confidence: 99%

Expression and analysis of presenilin 1 in a human neuronal system: localization in cell bodies and dendrites.

Cook

Sung

Golde

et al. 1996

Proc. Natl. Acad. Sci. U.S.A.

200

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Mutations in the recently identified presenilin 1 gene on chromosome 14 cause early onset familial Alzheimer disease (FAD). Herein we describe the expression and analysis of the protein coded by presenilin 1 (PS1) in NT2N neurons, a human neuronal model system. PS1 was expressed using recombinant Semliki Forest virions and detected by introduced antigenic tags or antisera to PS1-derived peptides. Immunoprecipitation revealed two major PS1 bands of approximately 43 and 50 kDa, neither of which were N-glycosylated or 0-glycosylated. Immunoreactive PS1 was detected in cell bodies and dendrites of NT2N neurons but not in axons or on the cell surface. PS1 was also detected in BHK cells, where it was also intracellular and colocalized with calnexin, a marker for the rough endoplasmic reticulum. A mutant form of PS1 linked to FAD did not differ from the wild-type protein at the light microscopic level. The model system described here will enable studies of the function of PS1 in human neurons and the role of mutant PS1 in FAD.Since mutations in the PS1 and PS2 genes result in early onset FAD that is quite similar to FAD in other pedigrees with APP mutations, the PS mutations may cause AD by altering the metabolism of APP and/or AP3, thereby accelerating amyloidogenesis. Considerable evidence suggests that neurons are a major source of the AP3 that forms amyloid deposits in AD (17, 18), and a recent study showed that within the brain PS1 and PS2 mRNAs are expressed primarily in neurons (19). For these reasons, it is important to study the biosynthesis and processing of these genes in neurons. To accomplish this goal, we developed a strategy to efficiently express and detect PS1 in a well characterized in vitro model of human neurons (NT2N cells) (20). We found that PS1 was localized in the cell body and dendrites of NT2N neurons but not on the cell surface or in axons.

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Developmental Regulation of Microtubule‐Associated Protein 2 Expression in Regions of Mouse Brain

Cited by 49 publications

References 60 publications

Deletion of a single allele of thePex11βgene is sufficient to cause oxidative stress, delayed differentiation and neuronal death in mouse brain

Deletion of a single allele of thePex11βgene is sufficient to cause oxidative stress, delayed differentiation and neuronal death in mouse brain

Dab2ip Regulates Neuronal Migration and Neurite Outgrowth in the Developing Neocortex

Expression and analysis of presenilin 1 in a human neuronal system: localization in cell bodies and dendrites.

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