Expression and function of Xenopus laevis p75(NTR) suggest evolution of developmental regulatory mechanisms

Neurotrophins signal through two different classes of receptors, members of the trk family of receptor tyrosine kinases, and p75 neurotrophin receptor (p75(NTR)), a member of the tumor necrosis factor receptor family. While neurotrophin binding to trks results in, among other things, increased cell survival, p75(NTR) has enigmatically been implicated in promoting both survival and cell death. Which of these two signals p75(NTR) imparts depends on the specific cellular context. Xenopus laevis is an excellent system in which to study p75(NTR) function in vivo because of its amenability to experimental manipulation. We therefore cloned partial cDNAs of two p75(NTR) genes from Xenopus, which we have termed p75(NTR)a and p75(NTR)b. We then cloned two different cDNAs, both of which encompass the full coding region of p75(NTR)a. Early in development both p75(NTR)a and p75(NTR)b are expressed in developing cranial ganglia and presumptive spinal sensory neurons, similar to what is observed in other species. Later, p75(NTR)a expression largely continues to parallel p75(NTR) expression in other species. However, Xenopus p75(NTR)a is additionally expressed in the neuroepithelium of the anterior telencephalon, all layers of the retina including the photoreceptor layer, and functioning axial skeletal muscle. Finally, misexpression of full length p75(NTR) and each of two truncated mutants in developing retina reveal that p75(NTR) probably signals for cell survival in this system. This result contrasts with the reported role of p75(NTR) in developing retinae of other species, and the possible implications of this difference are discussed.