Cortical circuits are characterized by layer-specific axonal arbors. Molecu
lar laminar cues are believed to direct the development of this specificity
. We have tested the hypothesis that ephrin-A5 is responsible for preventin
g layer 2/3 pyramidal cell axons from branching within layer 4 (Castellani
et al., 1998) by assessing the laminar specificity of axonal arbors in ephr
in-A5 knockout mice. We find that in barrel cortex of knockout mice, layer
2/3 pyramidal neurons form axonal arbors specifically in layers 2/3 and 5,
avoiding layer 4. This pattern of arborization is indistinguishable from th
at of wild-type littermates. Furthermore, we find that in wild-type mice, l
aminar patterns of ephrin-A5 expression differ between cortical areas despi
te the similarity of layer-specific local cortical circuits across areas. M
ost notably, ephrin-A5 is not expressed preferentially in layer 4 of wild-t
ype mouse barrel cortex. We conclude that ephrin-A5 is not responsible for
preventing the development of layer 2/3 pyramidal cell axonal arbors in lay
er 4 of mouse barrel cortex. These observations also suggest that if ephrin
-A5 plays a role in the emergence of layer-specific circuits, that role mus
t differ between cortical areas.