title: Uncoupling histogenesis from morphogenesis in the vertebrate embryo by collapse of the transneural tube potential.
abstract: We have shown that unidirectional pumping of Na+ out of the neural tube's luminal fluids in amphibian embryos produces a large potential difference (40-90 mV, lumen negative to the abluminal surface). This transneural tube potential (TNTP) is analogous to the Na+ dependent transepithelial potential (TEP) that exists across surface ectoderm. This TEP is retained in ectoderm after it is internalized when the neural folds fuse to form the neural tube. The TNTP can be markedly reduced for several hours by injection of the Na+ channel blockers amiloride or benzamil into the lumen by iontophoresis through microelectrodes. Here we describe the effect of TNTP modification on developmental anatomy. Axolotl embryos possessing a fused and closed neural tube (stage 21-23) were injected with either amiloride or benzamil and allowed to continue development for 36-52 hr. These were compared to control embryos injected with vehicle alone, or to embryos in which amiloride or benzamil was iontophoresed just beneath surface ectoderm. All embryos in which the TNTP was reduced were grossly defective. These were characterized by a disaggregation of the cells comprising the structures that had already begun to form (otic primordia, brain, spinal cord, notochord) as well as a failure in the development of new structures. Remarkably, some of these embryos displayed continuing development of external form in the complete absence of concomitant internal histogenesis. We discuss the ways in which a large endogenous voltage gradient associated with an epithelial potential difference (the TNTP) may be required both for the structural integrity of the early neuroepithelium, and a prerequisite for normal morphogenesis.
mesh_terms: D000557:Ambystoma / Q000196:embryology*; D000818:Animals; D001921:Brain / Q000196:embryology*; D004625:Embryo, Nonmammalian / Q000166:cytology*; D004848:Epithelium / Q000196:embryology; D005333:Fetus / Q000502:physiology; D009024:Morphogenesis / Q000502:physiology; D013116:Spinal Cord / Q000196:embryology*