Roles for EphA4-mediated intercellular signaling in corticogenesis and in the development of the peripheral somatosensory system

Abstract

The Eph family of receptor tyrosine kinases and its ligands, the ephrins, serve a variety of purposes during the development of many biological systems. Here, we have examined their role in nervous system development. Specifically, we used mice lacking one receptor, EphA4, to determine the function of that family member during normal development of the mouse. While many neurological phenotypes such as improper corticospinal and anterior commissure decussation, dendritic spine formation and auditory brainstem axon targeting have been attributed to insufficient EphA4 function during embryonic and neural development, we discovered two novel roles over the course of our investigation: EphA4 is essential to the proliferation of cortical progenitor cells during the development of the mammalian cerebral cortex and to the proper formation of the trigeminal somatosensory system’s primary sensory organ, the maxillary vibrissae. Our investigation of these two systems revealed a number of noteworthy additional findings including a novel Eph receptor/ephrin ligand binding pair, EphA4 and ephrin-B1, and possible evidence that neuronal presence may induce formation of target organs during vibrissal development. The two distinct studies presented in this doctoral dissertation have generated excitement in their respective fields, underscoring the continued relevance of the Eph/ephrin family of molecules to mammalian nervous system development.