EphA4 Has Distinct Functionality From EphA7 in the Corticothalamic System During Mouse Brain Development

摘要

Deciphering the molecular basis for guiding specific aspects of neocortical development remains a challenge due to the complexity of histogenic events and the vast array of protein interactions that mediate these events. The Eph family of receptor tyrosine kinases is implicated in a number of these neurodevelopmental activities. Eph receptors have been known to be capable of responding to several ephrin ligands within their respective subgroups, often eliciting similar downstream effects. However, several recent studies have reported specificity between receptor-ligand pairs within each subfamily, the functional relevance of which is not defined. Here, we show that a receptor of the EphA subfamily, EphA4, has distinct effects from its close relative EphA7 in the developing brain. Both EphA4 and EphA7 interact similarly with corresponding ligands expressed in the developing neocortex. However, only EphA7 shows strong interaction with ligands in the somatosensory thalamic nuclei; EphA4 affects only cortical neuronal migration with no visible effects on the guidance of CT axons, while EphA7 affects both cortical neuronal migration and CT axon guidance. Our data provide new evidence that Eph receptors in the same subfamily are not simply interchangeable, but functionally specified through selective interactions with distinct ligands in vivo.