Embryonic epithelial sodium transport, the resulting physiological potential, and neural development

Riyi Shi, Purdue University

Abstract

I am interested in the generation of endogenous electric fields associated with ionic currents driven through the embryo by the transepithelial potential of embryonic ectoderm. Here I present a description of two gradients in electrical potential; a voltage gradient under neural plate along the rostral/caudal axis, and a simultaneous gradient organized along the medial/lateral axis. Both gradients are not expressed until neurulation and disappear at its climax. This appearance and disappearance correlates with the shunting of current out of the lateral margins of the neural folds in rostral regions of the embryo, beginning at stage 15. However, it does not appear to be associated with the appearance of a more substantial current leak from the blastopore, beginning at gastrulation. This is evident since the blastopore current is still present after neural tube formation when intra-embryonic fields have been extinguished. I believe these extracellular electric fields both polarize the vertebrate embryo and serve as cues for morphogenesis and pattern formation. There are many direct experimental tests supporting this view and the ways this novel physiology may act in concert with the better recognized molecular controls of morphogenesis and differentiation. I have also shown that there is a potential difference across the wall of the neural tube. It appears that an amiloride/novobiocin sensitive sodium transport system, which is first observed in embryonic ectoderm, retains its physiology and polarity following the closure of the neural folds. Unidirectional transport of Na$\sp+$ out of the neural tube lumen is likely the mechanism which leads to a potential difference of 60-80 mV across the neural tube wall, with the lumen being negative with respect to the abluminal space. These mechanistic hypotheses are supported by the fact that this transneural tube potential (TNTP) can be collapsed by iontophoresis of Na$\sp+$ channel blockers, amiloride or benzamil, into the lumen. Interestingly but not surprisingly, the suppression of the TNTP leads to severe cranial defects and incomplete morphogenesis. These data strongly suggest that this unique physiology may help control the organization of the early nervous system.

Degree

Ph.D.

Advisors

Borgens, Purdue University.

Subject Area

Neurology

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