Disease relevance of Efna5

• During dental trigeminal axon pathfinding (embryonic days 12.5-13.5), ephrin-A2, ephrin-A4, and ephrin-A5 were evenly distributed in the trigeminal ganglion, whereas EphA7 was expressed in a subset of ganglion cells [1].
• Here we report that a subpopulation of ephrin-A5 null mice display neural tube defects resembling anencephaly in man [2].
• We now show the effects of several related cyclic imides: maleimides (S2, S2.1, S2.2, S3), glutarimides (S4, S5, S6), 4-aminoantipyrine derivatives (L1, F1, AL1, F1.14, F1.2) and sulfonated succinimides (RO1, FA, FE, FD, MC, DMC) on isolated rat liver mitochondria, B16-F10 melanoma cell line, peritoneal macrophages and different bacterial streams [3].

High impact information on Efna5

• This is caused by the failure of the neural folds to fuse in the dorsal midline, suggesting that ephrin-A5, in addition to its involvement in cell repulsion, can participate in cell adhesion [2].
• Genetic analysis of ephrin-A2 and ephrin-A5 shows their requirement in multiple aspects of retinocollicular mapping [4].
• These findings show that ephrin-A5 is required for the proper guidance and mapping of retinal axons in the mammalian midbrain [5].
• This defect is consistent with the high level of ephrin-A5 expression in the IC and the finding that retinal axon growth on membranes from wild-type IC is inhibited relative to that on membranes from ephrin-A5-/- IC [5].
• We have recently shown that ephrin-A5 signals within caveola-like domains of the plasma membrane upon engagement with its cognate Eph receptor, leading to increased adhesion of the cells to fibronectin [6].

Chemical compound and disease context of Efna5

• Ephrin-A5 and Integrin alpha6 are two of the known genes encoding cell adhesion molecules that are likely to be directly involved in neurulation because neural tube defects result when they are knocked out in mice [7].

Biological context of Efna5

• Hypothalamus expression of ephrin-A5 demarks distinct nuclei, persists throughout embryonic development, and can be seen also in the adult [8].
• In addition, Southern blot analysis of DNAs from interspecific backcross mice indicated that the mouse homologue Epl7 maps to a homologous region on chromosome 17 [9].
• In vivo gain of EphA receptor function, achieved through ectopic expression of ephrin-A5 in early cortical progenitors expressing EphA7, caused a transient wave of neural progenitor cell apoptosis, resulting in premature depletion of progenitors and a subsequent dramatic decrease in cortical size [10].
• To test whether ephrin-mediated repulsive cues participate in sorting the projections originating from distinct thalamic nuclei, we analyzed the organization of somatosensory and anterior cingulate afferents postnatally in mice lacking ephrin-A5 gene expression [11].
• Selective inhibition of spinal cord neurite outgrowth and cell survival by the Eph family ligand ephrin-A5 [12].

Anatomical context of Efna5

• In addition, ephrin-A1 and ephrin-A5 were seen in the forming blood vessels and alveolar bone, respectively [1].
• Prior to birth, ephrin-A1, ephrin-A5, EphA2, and EphA4 transcripts were present in the cuspal area of the dental papilla including the preodontoblasts [1].
• Here, we show complementary expression and binding for the receptor EphA5 in mouse retina and its ligands ephrin-A2 and ephrin-A5 in multiple retinal targets, including the major forebrain target, the dorsal lateral geniculate nucleus (dLGN) [13].
• This hypothesis was supported by our demonstration that EphA3 can direct retinal ganglion cell axon targeting and by studies of ephrin-A5(-/-) mutants that show that EphA receptor signaling controls the topographic innervation of the acromiotrapezius [14].
• In wild-type mice ephrin-A5 is expressed in a gradient in the somatosensory cortex during development [15].

Associations of Efna5 with chemical compounds

• Ephrin-A5 (AL-1/RAGS), a ligand for Eph receptor tyrosine kinases, repels retinal axons in vitro and has a graded expression in the superior colliculus (SC), the major midbrain target of retinal ganglion cells [5].
• Ephrin-A5 modulates cell adhesion and morphology in an integrin-dependent manner [6].

Other interactions of Efna5

• Video microscopic analyses show that AC1(brl/brl) axons have modified responses to ephrin-A5: the collapse of the growth cones occurs, but the rearward movement of the axon is arrested [16].

Analytical, diagnostic and therapeutic context of Efna5

• Expressing ephrin-A5 ectopically by in utero electroporation in the lateral cortex shifts the map of V1 medially, and expression within V1 disrupts its internal organization [17].
• Using in situ hybridization on whole-mounts and sections of mouse embryos we have visualized the pattern of expression for the Eph receptor ligand ephrin-A5 [8].
• In contrast, perfusion with AL-1/Ephrin-A5-IgG, an activator of REK7/EphA5, induces a sustained increase in normal synaptic transmission that partially mimics LTP [18].
• The sustained elevation of normal synaptic transmission could be attributable to a long-lasting binding of the AL-1/Ephrin-A5-IgG to the endogenous REK7/EphA5 receptor, as revealed by immunohistochemistry [18].
• The effects of AC1 loss of function in the retina are mimicked by the blockade of ephrin-A5 signaling in WT cocultures [16].

References