NrCAM Deletion Causes Topographic Mistargeting of Thalamocortical Axons to the Visual Cortex and Disrupts Visual Acuity

Demyanenko, Galina P.; Riday, Thorfinn T.; Tran, Tracy S.; Dalal, Jasbir S.; Darnell, Eli P.; Brennaman, Leann H.; Sakurai, Takeshi; Grumet, Martin; Philpot, Benjamin D.; Maness, Patricia F.

doi:10.1523/jneurosci.4467-10.2011

Cited by 55 publications

(58 citation statements)

References 57 publications

(99 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Neuronal IgSF CAMs associate at the cell surface to form homo-and heterophilic complexes and regulate neurite outgrowth and synaptic-contact formation (3). The expression levels of Thy-1 (46), cell adhesion molecule 3 (47), cell adhesion molecule L1 (48), NrCAM (49,50), neuroplastins (51), and basigin (52) are necessary for the proper establishment of functional neuronal circuitry. Thus, our data are perfectly in line with the fact that the above-mentioned CAMs have a precise expression profile tightly correlated to neuronal maturation.…”

Section: Discussionmentioning

confidence: 99%

A Cell Surface Biotinylation Assay to Reveal Membrane-associated Neuronal Cues: Negr1 Regulates Dendritic Arborization

Pischedda

Szczurkowska

Cirnaru

et al. 2014

Molecular & Cellular Proteomics

View full text Add to dashboard Cite

A complex and still not comprehensively resolved panel of transmembrane proteins regulates the outgrowth and the subsequent morphological and functional development of neuronal processes. In order to gain a more detailed description of these events at the molecular level, we have developed a cell surface biotinylation assay to isolate, detect, and quantify neuronal membrane proteins. When we applied our assay to investigate neuron maturation in vitro, we identified 439 differentially expressed proteins, including 20 members of the immunoglobulin superfamily. Among these candidates, we focused on Negr1, a poorly described cell adhesion molecule. We demonstrated that Negr1 controls the development of neurite arborization in vitro and in vivo. Given the tight correlation existing among synaptic cell adhesion molecules, neuron maturation, and a number of neurological disorders, our assay results are a useful tool that can be used to support the understanding of the molecular bases of physiological and pathological brain function. Genetic analysis indicates that 20% to 30% of the total open reading frame encodes for integral membrane proteins (1). Although less abundant than cytosolic proteins, membrane-passing proteins contribute to the regulation of all major cell processes and signaling pathways. In particular, membrane proteins play an important role in the establishment of functional neuronal circuitries during development. This process initially entails the growth, guidance, and stabilization of neuronal processes (axons and dendrites) in a timely, ordered manner involving cell surface molecules that sense the extracellular surroundings and activate signaling cascades (2).Then, specialized cell-to-cell connections, the synapses, are formed. These connections allow information to flow from one neuron to another and relay the precise juxtaposition and interactions between the pre-and postsynaptic membrane proteins to support their final functional establishment. Several families of synaptic transmembrane or membrane proteins, such as semaphorin, neuroligin, neurexin, and the immunoglobulin superfamily (IgSF), 1 are implicated in neurite formation and synapse establishment (3). However, the picture of membrane proteins expressed in neurons is still far from being completely resolved, and it is expected that many other key molecules are awaiting identification (4). Thus, uncovering the nature of the dynamic multiprotein complexes expressed at the plasma membrane will possibly strongly support the understanding of the mechanism controlling structural and functional neuron development. Here, we describe a biochemical approach to isolate and quantify proteins exposed at the extracellular side of the plasma membrane. Our assay utilized affinity purification on streptavidin resin of biotinylated membrane proteins extracted from a crude synaptosomal preparation. We combined this cell surface biotinylation assay with MS/MS analysis and label-free quantification to investigate protein patterns characterizing immature and m...

show abstract

Section: Discussionmentioning

confidence: 99%

A Cell Surface Biotinylation Assay to Reveal Membrane-associated Neuronal Cues: Negr1 Regulates Dendritic Arborization

Pischedda

Szczurkowska

Cirnaru

et al. 2014

Molecular & Cellular Proteomics

View full text Add to dashboard Cite

show abstract

“…Mechanistically, prethalamic (PTh-Th) and telencephalic (VTel-Th) guidepost cells (Molnár et al, 2012) may be the critical sources of Linx that promote extension of thalamocortical axons en route to the neocortex. Thalamic axon guidance cues, which include slits, netrin-1, neuregulin-1, ephrins, EphB1/2, Sema3A, and Sema3F (Demyanenko et al, 2011; Dufour et al, 2003; López-Bendito et al, 2006; Métin et al, 1997; Robichaux et al, 2014; Wright et al, 2007), may cooperatively function with Linx to establish early thalamocortical projections through the DTB en route to the cortex. Linx may also modulate expression or availability of thalamic axon guidance cues.…”

Section: Discussionmentioning

confidence: 99%

Linx Mediates Interaxonal Interactions and Formation of the Internal Capsule

Mandai¹,

Reimert²,

Ginty³

2014

Neuron

View full text Add to dashboard Cite

Summary During the development of forebrain connectivity, ascending thalamocortical and descending corticofugal axons first intermingle at the pallial-subpallial boundary to form the internal capsule (IC). However, the identity of molecular cues that guide these axons remains largely unknown. Here, we show that the transmembrane protein Linx is robustly expressed in the prethalamus and lateral ganglionic eminence-derived corridor and on corticofugal axons, but not on thalamocortical axons, and that mice with a null mutation of Linx exhibit a complete absence of the IC. Moreover, regional inactivation of Linx either in the prethalamus and LGE or in the neocortex leads to a failure of IC formation. Furthermore, Linx binds to thalamocortical projections and it promotes outgrowth of thalamic axons. Thus, Linx guides the extension of thalamocortical axons in the ventral forebrain and subsequently, it mediates reciprocal interactions between thalamocortical and corticofugal axons to form the IC.

show abstract

“…It is unclear whether this VAB-1-independent LAD-2 function is also conserved with mammalian L1CAMs. Given that both LAD-2 and mammalian L1CAMs are conserved semaphorin co-receptors (Castellani et al, 2000(Castellani et al, , 2004Demyanenko et al, 2011a;Falk et al, 2005;Wang et al, 2008), we surmise that this is likely.…”

Section: Lad-2 As a Non-canonical Ephrin Receptormentioning

confidence: 95%

EFN-4/Ephrin functions in LAD-2/L1CAM-mediated axon guidance in Caenorhabditis elegans

et al. 2016

View full text Add to dashboard Cite

During development of the nervous system, growing axons rely on guidance molecules to direct axon pathfinding. A well-characterized family of guidance molecules are the membrane-associated ephrins, which together with their cognate Eph receptors, direct axon navigation in a contact-mediated fashion. In C. elegans, the ephrin-Eph signaling system is conserved and is best characterized for their roles in neuroblast migration during early embryogenesis. This study demonstrates a role for the C. elegans ephrin EFN-4 in axon guidance. We provide both genetic and biochemical evidence that is consistent with the C. elegans divergent L1 cell adhesion molecule LAD-2 acting as a non-canonical ephrin receptor to EFN-4 to promote axon guidance. We also show that EFN-4 probably functions as a diffusible factor because EFN-4 engineered to be soluble can promote LAD-2-mediated axon guidance. This study thus reveals a potential additional mechanism for ephrins in regulating axon guidance and expands the repertoire of receptors by which ephrins can signal.

show abstract

NrCAM Deletion Causes Topographic Mistargeting of Thalamocortical Axons to the Visual Cortex and Disrupts Visual Acuity

Cited by 55 publications

References 57 publications

A Cell Surface Biotinylation Assay to Reveal Membrane-associated Neuronal Cues: Negr1 Regulates Dendritic Arborization

A Cell Surface Biotinylation Assay to Reveal Membrane-associated Neuronal Cues: Negr1 Regulates Dendritic Arborization

Linx Mediates Interaxonal Interactions and Formation of the Internal Capsule

EFN-4/Ephrin functions in LAD-2/L1CAM-mediated axon guidance in Caenorhabditis elegans

Contact Info

Product

Resources

About