Disease relevance of Efna2

• 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].
• As in the LGd, retinal axons from each eye terminate in discrete eye-specific zones in the MGN of rewired wild-type and ephrin-A2/A5 knockout mice [2].
• A tailored ELF-1 blocking peptide, containing a 12-amino acid HIV-1 TAT protein, readily crosses the cell membrane and enters into the nucleus of endothelial cells, leading to a marked reduction in the expression of ELF-1 gene targets including Tie2 and endothelial nitric oxide synthase [3].
• Methods: Female nude mice injected intraperitoneally with HeyA8 ovarian cancer cells were treated with either docetaxel alone or in combination with anti-angiogenic agents (AEE788-dual VEGFR and EGFR antagonist or EA5-monoclonal antibody against ephrin A2) [4].

High impact information on Efna2

• The expression domains of ELF-1, Mek4 and Sek indicate potential roles in embryonic patterning [5].
• In cell lines and embryos, ELF-1 is membrane bound by a phosphatidylinositol tail, a feature that may account for unique biological functions [5].
• The identification of ephrin-A2 and EphA7 as negative regulators of progenitor cell proliferation reveals a novel mechanism to control cell numbers in the brain [6].
• We here report the identification of an additional mechanism to control cell number in the brain: EphA7 induces ephrin-A2 reverse signaling, which negatively regulates neural progenitor cell proliferation [6].
• Here we found that in mice deficient for ephrin-A2, ephrin-A3 and ephrin-A5, eye-specific inputs segregated but the shape and location of eye-specific layers were profoundly disrupted [7].

Biological context of Efna2

• Cells in the neural stem cell niche in the adult brain proliferate more and have a shorter cell cycle in mice lacking ephrin-A2 [6].
• Subsequent molecular analysis demonstrated that both the -8 enhancer and the promoter depend on conserved Ets sites, which were bound in endothelial cells in vivo by Fli-1, Erg, and Elf-1 [8].
• In the present study, we proved the upregulation of ephrin-A2 in the denervated areas of the ipsilateral hippocampus following PP transections [9].
• Only the ephrin-A2 probe was tested on tadpole brain, yielding an appropriately graded expression pattern similar to the adult [10].
• Transactivation and expression studies support the hypothesis that Elf-1 activates TdT transcription in immature T and B cells [11].

Anatomical context of Efna2

• Here, we map the visual cortex (V1) in mice deficient for ephrin-A2, -A3, and -A5 functionally, using intrinsic signal optical imaging and microelectrode recording, and structurally, by anatomical tracing of thalamocortical projections [12].
• 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].
• EphA2, 3, and 4 receptors and one of their cognate ligands, ephrin-A2, are expressed by cells in the subventricular zone and ganglionic eminence of the embryonic day 14.5 telencephalon and by neural precursor cells in vitro [14].
• Ephrin-A2 and -A5 influence patterning of normal and novel retinal projections to the thalamus: conserved mapping mechanisms in visual and auditory thalamic targets [2].
• Many studies have demonstrated the involvement of the EphA family of receptor tyrosine kinases and their ligands, ephrin-A2 and -A5, in the development of the temporonasal axis of the retinotectal/collicular map, but the role of these molecules in optic nerve regeneration has not been well studied [15].

Associations of Efna2 with chemical compounds

• Identification and cloning of ELF-1, a developmentally expressed ligand for the Mek4 and Sek receptor tyrosine kinases [5].
• Binding of Elf-1 to the GL alpha promoter is inducible by lipopolysaccharide in nuclear extracts from splenic B cells [16].

Physical interactions of Efna2

• ELF-1 interacts with and transactivates the IgH enhancer pi site [17].

Regulatory relationships of Efna2

• We present strong evidence that ELF-1 is highly expressed in B-cells and is one of two major factors specifically interacting with the murine IgH enhancer pi site in B-cell nuclear extracts [17].

Other interactions of Efna2

• Elf-1 and B61 bind to the three full-length MDK1 isoforms with similar dissociation constants [18].
• It was previously shown that ephrin-A2, -A3 and -A5 bind to, and activate the EphA8 receptor tyrosine kinase, respectively [19].
• Both the model promoter and the macrophage-specific mouse and human c-fms promoters were activated in RAW264 cells by other Ets family transcription factors, Ets-2 and Elf-1 [20].
• Transcriptional regulation of the stem cell leukemia gene by PU.1 and Elf-1 [21].
• At the protein level, MITF, SCL, GATA-2, Elf-1 and c-fos were clearly detectable in sMCs [22].

References