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Gene Review

epha4a  -  eph receptor A4a

Danio rerio

Synonyms: EPH-like kinase 2, EphA4, Ephrin type-A receptor 4a, SO:0000704, Tyrosine-protein kinase receptor ZEK2, ...
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High impact information on epha4a

  • Function of the Eph-related kinase rtk1 in patterning of the zebrafish forebrain [1].
  • A new interface between otx2 and epha4a suggests that the rostralization stops at the caudal part of rhombomere 1 [2].
  • In support of this hypothesis, we show that it is possible to rescue boundary formation in fss(-) through the ectopic expression of EphA4, an anterior segment marker, in the paraxial mesoderm [3].
  • As gastrulation proceeds, both rtk1 and rtk2 are expressed within the axial hypoblast along the entire axis of the embryo [4].
  • However, in mosaic embryos, we observe that EphA4MO cells and EphA4-expressing cells sort from one another, an observation that is not predicted by the Eph-ephrin repulsion model but instead suggests that EphA4 promotes cell adhesion within the rhombomeres in which it is expressed [5].

Biological context of epha4a

  • EphA4 is required for cell adhesion and rhombomere-boundary formation in the zebrafish [5].
  • EphA4 was also detected during sensory organogenesis, in the developing ear, eye, nasal pits and lateral line [6].
  • In order to determine which components of EphA4 function may be primitive for gnathostomes, we cloned EphA4 from the lesser spotted catshark ( Scyliorhinus canicula) and examined its expression pattern during shark embryonic development [6].

Anatomical context of epha4a

  • Formation of the DMB is also defective as shown by a caudal expansion of diencephalic epha4a and pax6a expression into midbrain territory [7].
  • Third, activation of EphA4 leads to nonautonomous acquisition of columnar morphology and polarized relocalization of the centrosome and nucleus in cells on the opposite side of the forming boundary [8].
  • Second, activation of EphA4 leads to the cell-autonomous acquisition of a columnar morphology and apical redistribution of beta-catenin, aspects of epithelialization characteristic of cells at somite boundaries [8].
  • Consistent with the patterns reported for bony fish and tetrapods, we observed segmental expression of EphA4 in the developing hindbrain and later in the pharyngeal arches of shark embryos [6].
  • Analyses of EphA4 in mouse, chick, frog and zebrafish embryos have implicated this gene in a number of developmental processes, including maintenance of segmental boundaries, axon guidance, limb development, neural crest migration and patterning of the ear [6].

Other interactions of epha4a

  • This sorting-out process has been shown to involve repulsive interactions between cells expressing an Eph receptor tyrosine kinase, EphA4, and cells expressing its ephrinB ligands [5].


  1. Function of the Eph-related kinase rtk1 in patterning of the zebrafish forebrain. Xu, Q., Alldus, G., Macdonald, R., Wilkinson, D.G., Holder, N. Nature (1996) [Pubmed]
  2. Isthmus-to-midbrain transformation in the absence of midbrain-hindbrain organizer activity. Jászai, J., Reifers, F., Picker, A., Langenberg, T., Brand, M. Development (2003) [Pubmed]
  3. Anteroposterior patterning is required within segments for somite boundary formation in developing zebrafish. Durbin, L., Sordino, P., Barrios, A., Gering, M., Thisse, C., Thisse, B., Brennan, C., Green, A., Wilson, S., Holder, N. Development (2000) [Pubmed]
  4. Spatially regulated expression of three receptor tyrosine kinase genes during gastrulation in the zebrafish. Xu, Q., Holder, N., Patient, R., Wilson, S.W. Development (1994) [Pubmed]
  5. EphA4 is required for cell adhesion and rhombomere-boundary formation in the zebrafish. Cooke, J.E., Kemp, H.A., Moens, C.B. Curr. Biol. (2005) [Pubmed]
  6. Analysis of EphA4 in the lesser spotted catshark identifies a primitive gnathostome expression pattern and reveals co-option during evolution of shark-specific morphology. Freitas, R., Cohn, M.J. Dev. Genes Evol. (2004) [Pubmed]
  7. Pbx proteins cooperate with Engrailed to pattern the midbrain-hindbrain and diencephalic-mesencephalic boundaries. Erickson, T., Scholpp, S., Brand, M., Moens, C.B., Jan Waskiewicz, A. Dev. Biol. (2007) [Pubmed]
  8. Eph/Ephrin signaling regulates the mesenchymal-to-epithelial transition of the paraxial mesoderm during somite morphogenesis. Barrios, A., Poole, R.J., Durbin, L., Brennan, C., Holder, N., Wilson, S.W. Curr. Biol. (2003) [Pubmed]
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