Novel roles of the chemorepellent axon guidance molecule RGMa in cell migration and adhesion

The repulsive guidance molecule A (RGMa) is a contact-mediated axon guidance molecule that has significant roles in central nervous system (CNS) development. Here we have examined whether RGMa has novel roles in cell migration and cell adhesion outside the nervous system. RGMa was found to stimulate cell migration from Xenopus animal cap explants in a neogenin-dependent and BMP-independent manner. RGMa also stimulated the adhesion of Xenopus animal cap cells, and this adhesion was dependent on neogenin and independent of calcium. To begin to functionally characterize the role of specific domains in RGMa, we assessed the migratory and adhesive activities of deletion mutants. RGMa lacking the partial von Willebrand factor type D (vWF) domain preferentially perturbed cell adhesion, while mutants lacking the RGD motif affected cell migration. We also revealed that manipulating the levels of RGMa in vivo caused major migration defects during Xenopus gastrulation. We have revealed here novel roles of RGMa in cell migration and adhesion and demonstrated that perturbations to the homeostasis of RGMa expression can severely disrupt major morphogenetic events. These results have implications for understanding the role of RGMa in both health and disease

Identification of neurabin II as a novel doublecortin interacting protein.

The neuronal migration protein doublecortin (DCX) that associates with microtubules through a tandem DCX repeat, is required for the development of the complex architecture of the human cerebral cortex. Using a yeast two-hybrid screen with Dcx as bait, we have isolated neurabin II/spinophilin, an F-actin binding protein known to play a role in dendritic spine formation. The coiled-coil domain of neurabin II binds to a DCX region encompassing the C-terminal portion of the second DCX repeat and the N-terminal portion of the Ser/Pro-rich domain. Immunoprecipitation experiments with brain extracts show that neurabin II and Dcx interact in vivo. Several Dcx constructs that mimic human DCX mutant alleles failed to interact with neurabin II. Since Dcx and neurabin II colocalized in the developing and adult brain, a neurabin II–DCX heterodimer may be involved in neuronal migration and dendritic spine formation

bHLH gene expression in the Emx2-deficient dentate gyrus reveals defective granule cells and absence of migrating precursors.

Dentate gyrus development is uniquely characterized by the existence of migrating precursors. The production of precursors by the neuroepithelium is regulated by the proneural cascade of bHLH genes, which show distinctive expression patterns in dentate. Mice carrying a mutation in Emx2, a neuroepithelial transcription factor, lack the granule cell layer which forms most of the dentate, although the corresponding neuroepithelium is correctly specified. To understand this phenotype, we have analyzed the expression of proneural genes (bHLH gene family) and other markers in Emx2-deficient dentate. Here we show that, in the mutant dentate, expression of bHLH genes, Tenascin C and GFAP is abnormally confined to the germinal layer, as are most neuronal and astrocytic precursors. Additionally, Mash1 expression (marker of migrating precursors) is lost during development. Mutant granule cells show arrested migration and lack NeuroD2 expression. These results are evidence that in Emx2 mutants, migrating precursors (secondary matrix) and astrocytes are absent, the radial migration substrate impaired and granule cells deficiently differentiated. Our analysis gives insight into how a general defect caused by the absence of Emx2 translates into the dentate-specific phenotype

Identification of neurabin II as a novel doublecortin interacting protein

El estudio de las plagas que azotan determinados cultivos tiene un interés particular para el científico que observa y analiza desde su laboratorio, lo mismo que para el hombre del campo que tiene que enfrentarse de cerca contra los invasores de su predio. Al mismo tiempo hay, al lado de estas observaciones, otras no menos interesantes que se refieren a los colaboradores en esta gran tarea. 
 Mucho es lo que ya se adelanta en lo que respecta a los insectos llamados Predatores, e interesantes perspectivas se tienen en este aspecto de la lucha biológica; pero sin descender hasta los insectos, hallamos en escalas zoológicas superiores otros efectivos ayudantes del campo a los cuales es preciso defender

Expression pattern of the repulsive guidance molecules RGM A, B and C during mouse development

We have characterized for the first time the mouse expression patterns of the three known members of the novel RGM gene family ('Repulsive Axonal Guidance molecules' A, B and C) by in situ hybridization. Both RGM A and B are mostly expressed in central nervous system, while RGM C is exclusively expressed in all striated muscle and in the myocardium. RGM A and B appear at every level of the developing neural axis, where they colocalize to a large extent in the mantle layer, although only RGM A appears in the neuroepithelium, and only RGM B in the peripheral nervous system. During development, both RGM A and B appear also in lung and in limb cartilage, while RGM B has additional expression domains in pancreas

bHLH gene expression in the Emx2-deficient dentate gyrus reveals defective granule cells and absence of migrating precursors

Dentate gyrus development is uniquely characterized by the existence of migrating precursors. The production of precursors by the neuroepithelium is regulated by the proneural cascade of bHLH genes, which show distinctive expression patterns in dentate. Mice carrying a mutation in Emx2, a neuroepithelial transcription factor, lack the granule cell layer which forms most of the dentate, although the corresponding neuroepithelium is correctly specified. To understand this phenotype, we have analyzed the expression of proneural genes (bHLH gene family) and other markers in Emx2-deficient dentate. Here we show that, in the mutant dentate, expression of bHLH genes, Tenascin C and GFAP is abnormally confined to the germinal layer, as are most neuronal and astrocytic precursors. Additionally, Mash1 expression (marker of migrating precursors) is lost during development. Mutant granule cells show arrested migration and lack NeuroD2 expression. These results are evidence that in Emx2 mutants, migrating precursors (secondary matrix) and astrocytes are absent, the radial migration substrate impaired and granule cells deficiently differentiated. Our analysis gives insight into how a general defect caused by the absence of Emx2 translates into the dentate-specific phenotype