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neuronal marker (TAG-1) antibody - Yamamoto, M.; University of Tsukuba

RRID:AB_531775

Antibody ID

AB_531775

Target Antigen

neuronal marker (TAG-1) mouse, rat

Proper Citation

(DSHB Cat# 4D7/TAG1, RRID:AB_531775)

Clonality

monoclonal antibody

Comments

consolidated with AB_2315433 on 02/2018 by curator.; Application(s): FFPE,Function Blocking,Immunohistochemistry,Immunoprecipitation,Western Blot; Date Deposited: 02/02/1996

Host Organism

mouse

Vendor

DSHB Go To Vendor

Preterm birth disrupts cerebellar development by affecting granule cell proliferation program and Bergmann glia.

  • Iskusnykh IY
  • Exp. Neurol.
  • 2018 May 18

Literature context:


Abstract:

Preterm birth is a leading cause of long-term motor and cognitive deficits. Clinical studies suggest that some of these deficits result from disruption of cerebellar development, but the mechanisms that mediate cerebellar abnormalities in preterm infants are largely unknown. Furthermore, it remains unclear whether preterm birth and precocious exposure to the ex-utero environment directly disrupt cerebellar development or indirectly by increasing the probability of cerebellar injury, including that resulting from clinical interventions and protocols associated with the care of preterm infants. In this study, we analyzed the cerebellum of preterm pigs delivered via c-section at 91% term and raised for 10 days, until term-equivalent age. The pigs did not receive any treatments known or suspected to affect cerebellar development and had no evidence of brain damage. Term pigs sacrificed at birth were used as controls. Immunohistochemical analysis revealed that preterm birth did not affect either size or numbers of Purkinje cells or molecular layer interneurons at term-equivalent age. The number of granule cell precursors and Bergmann glial fibers, however, were reduced in preterm pigs. Preterm pigs had reduced proliferation but not differentiation of granule cells. qRT-PCR analysis of laser capture microdissected external granule cell layer showed that preterm pigs had a reduced expression of Ccnd1 (Cyclin D1), Ccnb1 (Cyclin B1), granule cell master regulatory transcription factor Atoh1, and signaling molecule Jag1. In vitro rescue experiments identified Jag1 as a central granule cell gene affected by preterm birth. Thus, preterm birth and precocious exposure to the ex-utero environment disrupt cerebellum by modulating expression of key cerebellar developmental genes, predominantly affecting development of granule precursors and Bergmann glia.

Funding information:
  • NICHD NIH HHS - T32 HD007491(United States)

Sonic Hedgehog Is a Remotely Produced Cue that Controls Axon Guidance Trans-axonally at a Midline Choice Point.

  • Peng J
  • Neuron
  • 2018 Jan 17

Literature context:


Abstract:

At the optic chiasm choice point, ipsilateral retinal ganglion cells (RGCs) are repelled away from the midline by guidance cues, including Ephrin-B2 and Sonic Hedgehog (Shh). Although guidance cues are normally produced by cells residing at the choice point, the mRNA for Shh is not found at the optic chiasm. Here we show that Shh protein is instead produced by contralateral RGCs at the retina, transported anterogradely along the axon, and accumulates at the optic chiasm to repel ipsilateral RGCs. In vitro, contralateral RGC axons, which secrete Shh, repel ipsilateral RGCs in a Boc- and Smo-dependent manner. Finally, knockdown of Shh in the contralateral retina causes a decrease in the proportion of ipsilateral RGCs in a non-cell-autonomous manner. These findings reveal a role for axon-axon interactions in ipsilateral RGC guidance, and they establish that remotely produced cues can act at axon guidance midline choice points.

Sonic Hedgehog switches on Wnt/planar cell polarity signaling in commissural axon growth cones by reducing levels of Shisa2.

  • Onishi K
  • Elife
  • 2017 Sep 8

Literature context:


Abstract:

Commissural axons switch on responsiveness to Wnt attraction during midline crossing and turn anteriorly only after exiting the floor plate. We report here that Sonic Hedgehog (Shh)-Smoothened signaling downregulates Shisa2, which inhibits the glycosylation and cell surface presentation of Frizzled3 in rodent commissural axon growth cones. Constitutive Shisa2 expression causes randomized turning of post-crossing commissural axons along the anterior-posterior (A-P) axis. Loss of Shisa2 led to precocious anterior turning of commissural axons before or during midline crossing. Post-crossing commissural axon turning is completely randomized along the A-P axis when Wntless, which is essential for Wnt secretion, is conditionally knocked out in the floor plate. This regulatory link between Shh and planar cell polarity (PCP) signaling may also occur in other developmental processes.

K+ Channel Kv3.4 Is Essential for Axon Growth by Limiting the Influx of Ca2+ into Growth Cones.

  • Huang CY
  • J. Neurosci.
  • 2017 Apr 26

Literature context:


Abstract:

Membrane excitability in the axonal growth cones of embryonic neurons influences axon growth. Voltage-gated K+ (Kv) channels are key factors in controlling membrane excitability, but whether they regulate axon growth remains unclear. Here, we report that Kv3.4 is expressed in the axonal growth cones of embryonic spinal commissural neurons, motoneurons, dorsal root ganglion neurons, retinal ganglion cells, and callosal projection neurons during axon growth. Our in vitro (cultured dorsal spinal neurons of chick embryos) and in vivo (developing chick spinal commissural axons and rat callosal axons) findings demonstrate that knockdown of Kv3.4 by a specific shRNA impedes axon initiation, elongation, pathfinding, and fasciculation. In cultured dorsal spinal neurons, blockade of Kv3.4 by blood depressing substance II suppresses axon growth via an increase in the amplitude and frequency of Ca2+ influx through T-type and L-type Ca2+ channels. Electrophysiological results show that Kv3.4, the major Kv channel in the axonal growth cones of embryonic dorsal spinal neurons, is activated at more hyperpolarized potentials and inactivated more slowly than it is in postnatal and adult neurons. The opening of Kv3.4 channels effectively reduces growth cone membrane excitability, thereby limiting excessive Ca2+ influx at subthreshold potentials or during Ca2+-dependent action potentials. Furthermore, excessive Ca2+ influx induced by an optogenetic approach also inhibits axon growth. Our findings suggest that Kv3.4 reduces growth cone membrane excitability and maintains [Ca2+]i at an optimal concentration for normal axon growth.SIGNIFICANCE STATEMENT Accumulating evidence supports the idea that impairments in axon growth contribute to many clinical disorders, such as autism spectrum disorders, corpus callosum agenesis, Joubert syndrome, Kallmann syndrome, and horizontal gaze palsy with progressive scoliosis. Membrane excitability in the growth cone, which is mainly controlled by voltage-gated Ca2+ (Cav) and K+ (Kv) channels, modulates axon growth. The role of Cav channels during axon growth is well understood, but it is unclear whether Kv channels control axon outgrowth by regulating Ca2+ influx. This report shows that Kv3.4, which is transiently expressed in the axonal growth cones of many types of embryonic neurons, acts to reduce excessive Ca2+ influx through Cav channels and thus permits normal axon outgrowth.

Migration of sympathetic preganglionic neurons in the spinal cord of a C3G-deficient mouse suggests that C3G acts in the reelin signaling pathway.

  • Yip YP
  • J. Comp. Neurol.
  • 2012 Oct 1

Literature context:


Abstract:

Proper positioning of sympathetic preganglionic neurons(SPNs) in the spinal cord is regulated by reelin signaling. SPNs in reeler (which lacks reelin), and in mice deficient in components of the reelin signaling pathway (reelin receptors VldlR and ApoER2, the cytoplasmic adaptor protein Dab1, Src and Fyn of the Src-family of non-receptor protein tyrosine kinases, and CrkL) are located adjacent to the central canal instead of in the intermediolateral column (IML) of the spinal cord. Events downstream of CrkL in control of SPN migration are unclear. The present study asks whether Rap guanine nucleotide exchange factor (GEF) 1 (C3G/Rap-gef1), a Ras family GEF that binds CrkL, could act downstream in the reelin signaling pathway in control of SPN migration. SPN migration was examined in a hypopmorphic C3G mutant mouse (C3G(gt)(/gt)) by using retrograde Dil labeling and NOS immunostaining. The results showed that SPN in the C3G(gt)/(gt) mutant migrate abnormally toward the central canal as in reeler. However, unlike reeler, levels of reelin in the C3G(gt)/(gt) spinal cord are normal, and Dab1 immunostaining is undetectable. These results provide genetic evidence that C3G regulates SPN migration, and suggest that C3G acts downstream in the reelin signaling pathway in control of SPN migration.

Funding information:
  • NIDA NIH HHS - P30 DA027827(United States)

Implication of perturbed axoglial apparatus in early pediatric multiple sclerosis.

  • Dhaunchak AS
  • Ann. Neurol.
  • 2012 May 23

Literature context:


Abstract:

Cerebrospinal fluid samples collected from children during initial presentation of central nervous system inflammation, who may or may not subsequently be diagnosed as having multiple sclerosis (MS), were subjected to large-scale proteomics screening. Unexpectedly, major compact myelin membrane proteins typically implicated in MS were not detected. However, multiple molecules that localize to the node of Ranvier and the surrounding axoglial apparatus membrane were implicated, indicating perturbed axon-glial interactions in those children destined for diagnosis of MS.

Funding information:
  • CIHR - 232519(Canada)
  • Medical Research Council - G0501898(United Kingdom)

Distinct roles of neuropilin 1 signaling for radial and tangential extension of callosal axons.

  • Hatanaka Y
  • J. Comp. Neurol.
  • 2009 May 20

Literature context:


Abstract:

Cortical excitatory neurons migrate from their origin in the ventricular zone (VZ) toward the pial surface. During migration, these neurons exhibit a stellate shape in the intermediate zone (IZ), transform into bipolar cells, and then initiate radial migration, extending a trailing process, which may lead to an axon. Here we examined the role of neuropilin 1 (NRP1) in these developmental events. Both NRP1 mRNA and protein were highly expressed in the IZ, where stellate-shaped cells were located. DiI labeling experiments showed that neuronal migration occurred normally in Nrp1 mutant mice up to embryonic day (E) 14.5, the latest day to which the mutant survives, with only subtle axonal defasciculation. However, interference with Nrp1 signaling at a later stage caused pathfinding errors: when a dominant negative form of Nrp1 was electroporated into the cortical VZ cells at E12.5 or E15.5 and examined perinatally, guidance errors were found in tangential axonal extension toward the midline. In contrast, no significant effect was noted on the migration of cortical excitatory neurons. These findings indicate that NRP1 plays an important role in the guidance of callosal axons originating from cortical excitatory neurons but does not support a role in their migration. Moreover, insofar as radial axonal extension within the cortical plate was unaffected, the present findings imply that molecular mechanisms for the axonal extension of excitatory neurons within the cortical plate are distinct from those in the white matter.

Funding information:
  • NIAAA NIH HHS - AA09838(United States)

Contactin-2/TAG-1-directed autoimmunity is identified in multiple sclerosis patients and mediates gray matter pathology in animals.

  • Derfuss T
  • Proc. Natl. Acad. Sci. U.S.A.
  • 2009 May 19

Literature context:


Abstract:

Gray matter pathology is increasingly recognized as an important feature of multiple sclerosis (MS), but the nature of the immune response that targets the gray matter is poorly understood. Starting with a proteomics approach, we identified contactin-2/transiently expressed axonal glycoprotein 1 (TAG-1) as a candidate autoantigen recognized by both autoantibodies and T helper (Th) 1/Th17 T cells in MS patients. Contactin-2 and its rat homologue, TAG-1, are expressed by various neuronal populations and sequestered in the juxtaparanodal domain of myelinated axons both at the axonal and myelin sides. The pathogenic significance of these autoimmune responses was then explored in experimental autoimmune encephalitis models in the rat. Adoptive transfer of TAG-1-specific T cells induced encephalitis characterized by a preferential inflammation of gray matter of the spinal cord and cortex. Cotransfer of TAG-1-specific T cells with a myelin oligodendrocyte glycoprotein-specific mAb generated focal perivascular demyelinating lesions in the cortex and extensive demyelination in spinal cord gray and white matter. This study identifies contactin-2 as an autoantigen targeted by T cells and autoantibodies in MS. Our findings suggest that a contactin-2-specific T-cell response contributes to the development of gray matter pathology.

Cdk5 selectively affects the migration of different populations of neurons in the developing spinal cord.

  • Yip YP
  • J. Comp. Neurol.
  • 2007 Jul 10

Literature context:


Abstract:

It has been shown that cyclin-dependent kinase 5 (Cdk5) is crucial for neuronal migration and survival in the brain. However, the role of Cdk5 in neuronal migration in the spinal cord has never been investigated. The present study is the first to show that Cdk5 affects the migration of different populations of neurons in the developing spinal cord. In the absence of Cdk5, at least four neuronal populations failed to migrate to their final destinations: sympathetic and parasympathetic preganglionic neurons, as well as dorsally originating and ventrally originating (U-shaped group) diaphorase-positive dorsal horn interneurons. In contrast, the migration of somatic motor neurons and various types of ventral and dorsal interneurons was unaffected by the absence of Cdk5. Moreover, our results suggest that Cdk5-dependent migration in the developing spinal cord is axon- or glial fiber-mediated. Finally, our results show that sympathetic preganglionic neurons and somatic motor neurons in Cdk5-deficient mice continue to extend processes and project toward their normal target areas, suggesting that Cdk5 has no obvious effects on axonal outgrowth and guidance mechanisms of these two neuronal populations in spinal cord development.

Funding information:
  • NIA NIH HHS - R37 AG008796(United States)

Soluble adenylyl cyclase is required for netrin-1 signaling in nerve growth cones.

  • Wu KY
  • Nat. Neurosci.
  • 2006 Oct 26

Literature context:


Abstract:

Growth cones at the tips of nascent and regenerating axons direct axon elongation. Netrin-1, a secreted molecule that promotes axon outgrowth and regulates axon pathfinding, elevates cyclic AMP (cAMP) levels in growth cones and regulates growth cone morphology and axonal outgrowth. These morphological effects depend on the intracellular levels of cAMP. However, the specific pathways that regulate cAMP levels in response to netrin-1 signaling are unclear. Here we show that 'soluble' adenylyl cyclase (sAC), an atypical calcium-regulated cAMP-generating enzyme previously implicated in sperm maturation, is expressed in developing rat axons and generates cAMP in response to netrin-1. Overexpression of sAC results in axonal outgrowth and growth cone elaboration, whereas inhibition of sAC blocks netrin-1-induced axon outgrowth and growth cone elaboration. Taken together, these results indicate that netrin-1 signals through sAC-generated cAMP, and identify a fundamental role for sAC in axonal development.

Funding information:
  • NHGRI NIH HHS - R01 HG004090-03(United States)

Distribution of EphB receptors and ephrin-B1 in the developing vertebrate spinal cord.

  • Jevince AR
  • J. Comp. Neurol.
  • 2006 Aug 10

Literature context:


Abstract:

Contact-dependent interactions between EphB receptors and ephrin-B ligands mediate a variety of cell-cell communication events in the developing and mature central nervous system (CNS). These predominantly repulsive interactions occur at the interface between what are considered to be mutually exclusive EphB and ephrin-B expression domains. We previously used receptor and ligand affinity probes to show that ephrin-B ligands are expressed in the floor plate and within a dorsal region of the embryonic mouse spinal cord, while EphB receptors are present on decussated segments of commissural axons that navigate between these ephrin-B domains. Here we present the generation and characterization of two new monoclonal antibodies, mAb EfB1-3, which recognizes EphB1, EphB2, and EphB3, and mAb efrnB1, which is specific for ephrin-B1. We use these reagents and polyclonal antibodies specific for EphB1, EphB2, EphB3, or ephrin-B1 to describe the spatiotemporal expression patterns of EphB receptors and ephrin-B1 in the vertebrate spinal cord. Consistent with affinity probe binding, we show that EphB1, EphB2, and EphB3 are each preferentially expressed on decussated segments of commissural axons in vivo and in vitro, and that ephrin-B1 is expressed in a dorsal domain of the spinal cord that includes the roof plate. In contrast to affinity probe binding profiles, we show here that EphB1, EphB2, and EphB3 are present on the ventral commissure, and that EphB1 and EphB3 are expressed on axons that compose the dorsal funiculus. In addition, we unexpectedly find that mesenchymal cells, which surround the spinal cord and dorsal root ganglion, express ephrin-B1.

Funding information:
  • PHS HHS - HHSN272200900018C(United States)

A role for Nr-CAM in the patterning of binocular visual pathways.

  • Williams SE
  • Neuron
  • 2006 May 18

Literature context:


Abstract:

Retinal ganglion cell (RGC) axons diverge within the optic chiasm to project to opposite sides of the brain. In mouse, contralateral RGCs are distributed throughout the retina, whereas ipsilateral RGCs are restricted to the ventrotemporal crescent (VTC). While repulsive guidance mechanisms play a major role in the formation of the ipsilateral projection, little is known about the contribution of growth-promoting interactions to the formation of binocular visual projections. Here, we show that the cell adhesion molecule Nr-CAM is expressed by RGCs that project contralaterally and is critical for the guidance of late-born RGCs within the VTC. Blocking Nr-CAM function causes an increase in the size of the ipsilateral projection and reduces neurite outgrowth on chiasm cells in an age- and region-specific manner. Finally, we demonstrate that EphB1/ephrin-B2-mediated repulsion and Nr-CAM-mediated attraction comprise distinct molecular programs that each contributes to the proper formation of binocular visual pathways.

Funding information:
  • NCI NIH HHS - P30 CA51008(United States)

A novel cAMP-dependent pathway activates neuronal integrin function in retinal neurons.

  • Ivins JK
  • J. Neurosci.
  • 2004 Feb 4

Literature context:


Abstract:

Retinal neurons lose the ability to attach to and extend neurites on substrata of laminin-1 (LN-1) during late embryogenesis, in a time frame that corresponds to target innervation. Although this developmental loss correlates with a modest downregulation of integrin expression, we have shown previously that these neurons use the same laminin-binding integrins for outgrowth on other laminin isoforms to which responsivity has not been lost (Ivins et al., 1998), suggesting that integrin functional states may be a critical point of regulation. Consistent with this view, expression of an activated mutant of R-ras, an activator of integrin function, restores integrin-dependent outgrowth of late embryonic retinal neurons on LN-1 (Ivins et al., 2000). Because cyclic nucleotides have been implicated in the regulation of integrin function in non-neuronal cells, as well as in the regulation of growth cone responses to various axon growth inhibitors, we asked whether raising cAMP levels in late embryonic retinal neurons could activate neuronal integrin function and restore neurite outgrowth on LN-1. We find that, similar to R-ras expression, raising cAMP levels in these neurons promotes alpha6beta1 integrin-dependent neurite outgrowth. Surprisingly, these effects of cAMP are independent of protein kinase A and the EPAC (exchange protein directly activated by cAMP)/Rap pathway and suggest the existence of a novel cAMP-dependent mechanism.

Funding information:
  • Intramural NIH HHS - Z01 NS002787-19(United States)

Spatial regulation of axonal glycoprotein expression on subsets of embryonic spinal neurons.

  • Dodd J
  • Neuron
  • 1988 Apr 6

Literature context:


Abstract:

The identification of surface proteins restricted to subsets of embryonic axons and growth cones may provide information on the mechanisms underlying axon fasciculation and pathway selection in the vertebrate nervous system. We describe here the characterization of a 135 kd cell surface glycoprotein, TAG-1, that is expressed transiently on subsets of embryonic spinal cord axons and growth cones. TAG-1 is immunochemically distinct from the cell adhesion molecules N-CAM and L1 (NILE) and is expressed on commissural and motor neurons over the period of initial axon extension. Moreover, TAG-1 and L1 appear to be segregated on different segments of the same embryonic spinal axons. These observations provide evidence that axonal guidance and pathway selection in vertebrates may be regulated in part by the transient and selective expression of distinct surface glycoproteins on subsets of developing neurons.

Funding information:
  • NHGRI NIH HHS - P01 HG004120(United States)