The invariant left–right asymmetry of animal body plans raises fascinating questions in cell, developmental, evolutionary, and neuro‐biology. While intermediate mechanisms (e.g., asymmetric gene expression) have been well‐characterized, very early steps remain elusive. Recent studies suggested a candidate for the origins of asymmetry: rotary movement of extracellular morphogens by cilia during gastrulation. This model is intellectually satisfying, because it bootstraps asymmetry from the intrinsic biochemical chirality of cilia. However, conceptual and practical problems remain with this hypothesis, and the genetic data is (...) consistent with a different mechanism. Based on wide‐ranging data on ion fluxes and motor protein action in a number of species, a model is proposed whereby laterality is generated much earlier, by asymmetric transport of ions, which results in pH/voltage gradients across the midline. These asymmetries are in turn generated by a new candidate for “step 1”: asymmetric localization of electrogenic proteins by cytoplasmic motors. BioEssays 25:1002–1010, 2003. © 2003 Wiley Periodicals, Inc. (shrink)

The medium surrounding cells either in culture or in tissues contains a chemical mix varying with cell state. As solutes move in and out of the cytoplasmic compartment they set up characteristic signatures in the cellular boundary layers. These layers are complex physical and chemical environments the profiles of which reflect cell physiology and provide conduits for intercellular messaging. Here we review some of the most relevant characteristics of the extracellular/intercellular space. Our initial focus is primarily on cultured cells but (...) we extend our consideration to the far more complex environment of tissues, and discuss how chemical signatures in the boundary layer can or may affect cell function. Critical to the entire essay are the methods used, or being developed, to monitor chemical profiles in the boundary layers. We review recent developments in ultramicro electrochemical sensors and tailored optical reporters suitable for the task in hand. (shrink)