Recent experiments on the genetic control of eye development have opened up a completely new perspective on eye evolution. The demonstration that targeted expression of one and the same master ...control gene, that is, Pax6 can induce the formation of ectopic eyes in both insects and vertebrates, necessitates a reconsideration of the dogma of a polyphyletic origin of the various eye types in all the animal phyla. The involvement of Pax6 and six1 and six3 genes, which encode highly conserved transcription factors, in the genetic control of eye development in organisms ranging from planarians to humans argues strongly for a monophyletic origin of the eye. Because transcription factors can control the expression of any target gene provided it contains the appropriate gene regulatory elements, the conservation of the genetic control of eye development by Pax6 among all bilaterian animals is not due to functional constraints but a consequence of its evolutionary history. The prototypic eyes postulated by Darwin to consist of two cells only, a photoreceptor and a pigment cell, were accidentally controlled by Pax6 and the subsequent evolution of the various eye types occurred by building onto this original genetic program. A hypothesis of intercalary evolution is proposed that assumes that the eye morphogenetic pathway is progressively modified by intercalation of genes between the master control genes on the top of the hierarchy and the structural genes like rhodopsin at the bottom. The recruitment of novel genes into the eye morphogenetic pathway can be due to at least two different genetic mechanisms, gene duplication and enhancer fusion.In tracing back the evolution of eyes beyond bilaterians, we find highly developed eyes in some box-jellyfish as well as in some Hydrozoans. In Hydrozoans the same orthologous six genes (six1 and six3) are required for eye regeneration as in planarians, and in the box jellyfish Tripedalia a pax B gene, which may be a precursor of Pax6, was found to be expressed in the eyes. In contrast to the adults, which have highly evolved eyes, the Planula larva of Tripedalia has single- celled photoreceptors similar to some unicellular protists. For the origin of photoreceptor cells in metazoa, I propose two hypotheses, one based on cellular differentiation and a more speculative one based on symbiosis. The former assumes that photoreceptor cells originated from a colonial protist in which all the cells were photosensitive and subsequent cellular differentiation to give rise to photoreceptor cells. The symbiont hypothesis, which I call the Russian doll model, assumes that photosensitivity arose first in photosynthetic cyanobacteria that were subsequently taken up into red algae as primary chloroplasts. The red algae in turn were taken up by dinoflagellates as secondary chloroplasts and in some species evolved into the most sophisticated eye organelles, as found, for example, in some dinoflagellates like Erythropsis and Warnovia, which lack chloroplasts. Because dinoflagellates are commonly found as symbionts in cnidarians, the dinoflagellates may have transferred their photoreceptor genes to cnidarians. In cnidarians such as Tripedalia the step from photoreceptor organelles to multicellular eyes has occurred. These two hypotheses, the cellular differentiation and the symbiont hypothesis, are not mutually exclusive and are the subject of further investigations.
Pax 6 genes from various animal phyla are capable of inducing ectopic eye development, indicating that
Pax 6 is a master control gene for eye morphogenesis. It is proposed that the various eye-types ...found in metazoa are derived from a common prototype, monophyletically, by a mechanism called intercalary evolution.
A principal function of the medial frontal cortex, in particular the anterior cingulate cortex (ACC), is to monitor action. The error-related negativity (ERN, or N(E)), an event-related brain ...potential, reflects medial frontal action-monitoring processes. Specifically, the error-detection theory of the ERN states that the ERN reflects ACC processing that is directly related to detecting the error. This theory predicts that ERN and ACC activity should increase directly with the dissimilarity of the error from the correct response, with similarity defined with respect to the common movement features of the responses. In contrast, the conflict-detection theory claims that ACC and ERN activity represent the detection of response conflict. This theory predicts that the activity should increase directly with the similarity of the error and the correct response. To test these theories, we investigated the effects of response similarity and conflict on the ERN, using a task that involved hand and foot movements. ERN activity was largest under conditions of high response conflict, where the error was similar to the correct response. This finding favors the conflict-detection theory over the error-detection theory, although the ERN was not associated with posterror slowing, as predicted by proponents of both theories. Discrepancies between our results and those of past studies may stem from the use in previous studies of four-finger response tasks which are subject to unique physiological and biomechanical constraints. We conclude that the ERN reflects medial frontal activity involved in the detection or affective processing of response conflict.
We report the observation of neural processing that occurs within 265 milliseconds after outcome stimuli that inform human participants about gains and losses in a gambling task. A negative-polarity ...event-related brain potential, probably generated by a medial-frontal region in or near the anterior cingulate cortex, was greater in amplitude when a participant's choice between two alternatives resulted in a loss than when it resulted in a gain. The sensitivity to losses was not simply a reflection of detecting an error; gains did not elicit the medial-frontal activity when the alternative choice would have yielded a greater gain, and losses elicited the activity even when the alternative choice would have yielded a greater loss. Choices made after losses were riskier and were associated with greater loss-related activity than choices made after gains. It follows that medial-frontal computations may contribute to mental states that participate in higher level decisions, including economic choices.
The Drosophila gene eyeless (ey) encodes a transcription factor with both a paired domain and a homeodomain. It is homologous to the mouse Small eye (Pax-6) gene and to the Aniridia gene in humans. ...These genes share extensive sequence identity, the position of three intron splice sites is conserved, and these genes are expressed similarly in the developing nervous system and in the eye during morphogenesis. Loss-of-function mutations in both the insect and in the mammalian genes have been shown to lead to a reduction or absence of eye structures, which suggests that ey functions in eye morphogenesis. By targeted expression of the ey complementary DNA in various imaginal disc primordia of Drosophila, ectopic eye structures were induced on the wings, the legs, and on the antennae. The ectopic eyes appeared morphologically normal and consisted of groups of fully differentiated ommatidia with a complete set of photoreceptor cells. These results support the proposition that ey is the master control gene for eye morphogenesis. Because homologous genes are present in vertebrates, ascidians, insects, cephalopods, and nemerteans, ey may function as a master control gene throughout the metazoa.
A Drosophila gene that contains both a paired box and a homeobox and has extensive sequence homology to the mouse Pax-6 (Small eye) gene was isolated and mapped to chromosome IV in a region close to ...the eyeless locus. Two spontaneous mutations, ey2 and eyR, contain transposable element insertions into the cloned gene and affect gene expression, particularly in the eye primordia. This indicates that the cloned gene encodes ey. The finding that ey of Drosophila, Small eye of the mouse, and human Aniridia are encoded by homologous genes suggests that eye morphogenesis is under similar genetic control in both vertebrates and insects, in spite of the large differences in eye morphology and mode of development
We found that medial frontal cortex activity associated with action monitoring (detecting errors and behavioral conflict) depended on activity in the lateral prefrontal cortex. We recorded the ...error-related negativity (ERN), an event-related brain potential proposed to reflect anterior cingulate action monitoring, from individuals with lateral prefrontal damage or age-matched or young control participants. In controls, error trials generated greater ERN activity than correct trials. In individuals with lateral prefrontal damage, however, correct-trial ERN activity was equal to error-trial ERN activity. Lateral prefrontal damage also affected corrective behavior. Thus the lateral prefrontal cortex seemed to interact with the anterior cingulate cortex in monitoring behavior and in guiding compensatory systems.
To generate transgenic planarians we used a set of versatile vectors for animal transgenesis based on the promiscuous transposons, mariner, Hermes and piggyBac, and a universal enhanced GFP (EGFP) ...marker system with three Pax6 dimeric binding sites, the 3xP3-EGFP developed by Berghammer et al. Berghammer, A. J., Klinger, M. & Wimmer, E. A. (1999) Nature 402, 370-371. This marker is expressed specifically in the eyes of various arthropod taxa. Upon microinjection into the parenchyma of adult planarians and subsequent electroporation, these vectors transpose efficiently into the planarian genome. One of the cell types transformed are the totipotent "neoblast" stem cells present in the adults, representing 30% of total cells. The neoblast represents a unique cell type with the capacity to proliferate and to differentiate into all somatic cell types as well as into germ cells. All three transposon vectors have high transformation efficiency, but only Hermes and piggyBac show stable integration. The mariner vector is frequently lost presumably because of the presence of active mariner-type transposons in the genome of the Girardia tigrina. Transformed animals are mosaics containing both transformed and untransformed neoblasts. These differentiate to form EGFP-positive and -negative photoreceptor cells. Such mosaicism is maintained through several cycles of regeneration induced by decapitation or asexual reproduction. Transformed neoblasts also contribute to the germ line, and can give rise to pure transgenic planarian lines in which EGFP is expressed in all photoreceptor cells after sexual reproduction. The presence of the transgenes was confirmed by PCR, plasmid rescue assay, inverse PCR, and Southern blotting. Our results with the 3xP3-EGFP marker confirm the presence of Pax6 activity in the differentiated photoreceptor cells of planarian eyes. Transgenesis will be an important tool to dissect developmental molecular mechanisms in planarian regeneration, development and stem cell biology, and may also be an entry point to analyze the biology of parasitic Platyhelminthes.
Evidence suggests that a hyperactive frontal-striatal-thalamic-frontal circuit is associated with the symptoms of obsessive-compulsive disorder (OCD), but there is little agreement about the function ...of the exaggerated activity. We report electrophysiological evidence suggesting that part of this system monitors events and generates error signals when the events conflict with an individual's internal standards or goals. Nine individuals with OCD and 9 age-, sex-, and education-matched control participants performed a speeded reaction time task. The error-related negativity, an event-related brain potential component that reflects action-monitoring processes, was enhanced in the individuals with OCD. The magnitude of this enhancement correlated with symptom severity. Dipole modeling suggested that the locus of the enhancement corresponded to medial frontal regions, possibly the anterior cingulate cortex.
The anterior determinant bicoid (bcd) of Drosophila is a homeodomain protein. It forms an anterior-to-posterior gradient in the embryo and activates, in a concentration-dependent manner, several ...zygotic segmentation genes during blastoderm formation. Its posterior counterpart, the homeodomain transcription factor caudal (cad), forms a concentration gradient in the opposite direction, emanating from evenly distributed messenger RNA in the egg. In embryos lacking bcd activity as a result of mutation, the cad gradient fails to form and cad becomes evenly distributed throughout the embryo. This suggests that bcd may act in the region-specific control of cad mRNA translation. Here we report that bcd binds through its homeodomain to cad mRNA in vitro, and exerts translational control through a bcd-binding region of cad mRNA.
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