The retina pigment epithelium (RPE) is a highly specialised epithelium that serves as a multifunctional and indispensable component of the vertebrate eye. Although a great deal of attention has been paid to its transdifferentiation capabilities and its ancillary functions in neural retina development, little is known about the molecular mechanisms that specify the RPE itself. Recent advances in our understanding of the genetic network that controls the progressive specification of the eye anlage in vertebrates have provided some of the initial (...) cues to the mechanisms responsible for RPE patterning. Here, we have outlined many recent findings that suggest that a limited number of transcription factors, including Otx2, Mitf and Pax6 and a few signalling cascades, are the elements required for the onset of RPE specification in vertebrates. Furthermore, using this information and the data available on the specification of the pigmented cells of primitive chordates, we have ventured some hypotheses on the origin of RPE cells during evolution. BioEssays 26:766–777, 2004. © 2004 Wiley Periodicals, Inc. (shrink)

The neurosciences are generating new findings regarding genetic and neurobiological aspects of the pathophysiology of mental disorders. Especially, certain genetic risk factors like neuregulin-1 seem to predispose individuals to a psychotic phenotype beyond the limits of traditional classificatory boundaries between organic psychoses in Alzheimer’s disease, bipolar affective disorder and schizophrenia. Little, however, is known about how such genetic risk factors actually confer an increased risk for psychosis in an individual patient. A gap between neuroscientific findings and psychopathological phenomena exists. The (...) main hypothesis how this gap may be bridged is that mental disorders arise as a consequence of dysfunctions of normal mental functions. Modularity may provide a useful conceptual framework in that temporally and/or spatially stable neural circuits subserve certain physiological functions of the human brain, which become the target of pathophysiological effectors. The idea of a modular construction of the human brain is based on neurobiological evidence regarding the columnar architecture of the cerebral cortex, which provides certain elementary analytical functions. Modular dysfunctions may be assessed with methods of experimental psychopathology, in which subsystems of brain functions are tested with standardized experimental psychological techniques (functional psychopathology). The main questions here are how to define a module, and whether the classical neuroscientific definitions can be used to characterize higher integrative functions of the human brain. (shrink)