New directions in craniofacial morphogenesis

The vertebrate head is an extremely complicated structure: development of the head requires tissue-tissue interactions between derivates of all the germ layers and coordinated morphogenetic movements in three dimensions. In this review, we highlight a number of recent embryological studies, using chicken, frog, zebrafish and mouse, which have identified crucial signaling centers in the embryonic face. These studies demonstrate how small variations in growth factor signaling can lead to a diversity of phenotypic outcomes. We also discuss novel genetic studies, in human, mouse and zebrafish, which describe cell biological mechanisms fundamental to the growth and morphogenesis of the craniofacial skeleton. Together, these findings underscore the complex interactions leading to species-specific morphology. These and future studies will improve our understanding of the genetic and environmental influences underlying human craniofacial anomalies.     

Mechanisms of madness: evolutionary psychiatry without evolutionary psychology

Delusions are currently characterised as false beliefs produced by incorrect inference about external reality (DSM IV). This inferential conception has proved hard to link to explanations pitched at the level of neurobiology and neuroanatomy. This paper provides that link via a neurocomputational theory, based on evolutionary considerations, of the role of the prefrontal cortex in regulating offline cognition. When pathologically neuromodulated the prefrontal cortex produces hypersalient experiences which monopolise offline cognition. The result is characteristic psychotic experiences and patterns of thought. This bottom-up account uses neural network theory to integrate recent theories of the role of dopamine in delusion with the insights of inferential accounts. It also provides a general model for evolutionary psychiatry which avoids theoretical problems imported from evolutionary psychology.     

Discrimination of jittered sonar echoes by the echolocating bat,Eptesicus fuscus: The shape of target images in echolocation

1. Behavioral experiments with jittering echoes examined acoustic images of sonar targets in the echolocating bat, Eptesicus fuscus, along the echo delay or target range axis. Echo phase, amplitude, bandwidth, and signal-to-noise ratio were manipulated to assess the underlying auditory processes for image formation. 2. Fine delay acuity is about 10 ns. Calibration and control procedures indicate that this represents temporal acuity rather than spectral discrimination. Jitter discrimination curves change in phase when the phase of one jittering echo is shifted by 180 degrees relative to the other, showing that echo phase is involved in delay estimation. At an echo detectability index of about 36 dB, fine acuity is 40 ns, which is approximately as predicted for the delay accuracy of an ideal receiver. 3. Compound performance curves for 0 degrees and 180 degrees phase conditions match the crosscorrelation function of the echoes. The locations of both 0 degrees and 180 degrees phase peaks in the performance curves shift along the time axis by an amount that matches neural amplitude-latency trading in Eptesicus, confirming a temporal basis for jitter discrimination.     

Role of cell-cycle in regulating neuroepithelial cell shape during bending of the chick neural plate

Summary Neuroepithelial cells transform from spindle-shaped to wedge-shaped within the median and paired dorsolateral hinge points of the bending neural plate, but the mechanisms underlying these localized changes are unclear. This study was designed to evaluate further the hypothesis that localized wedging of neuroepithelial cells during bending involves basal cellular expansion resulting from alteration of the cell-cycle. Neurulating chick embryos were treated with tritiated thymidine, and transverse sections through the midbrain were examined autoradiographically. Parameters of the cell-cycle as well as nuclear position and size were assessed in the median hinge point, which contains predominantly wedge-shaped cells, and in adjacent lateral areas of the neural plate, which contain predominantly spindle-shaped cells. Both the DNA-synthetic phase and non-DNA synthetic portion of the cell-cycle were significantly longer in the median hinge point than in lateral neuroepithelial areas, some nuclei in both regions were located basally during these phases, and virtually all basal nuclei in the median hinge point were large. Additionally, the mitotic phase was significantly shorter in the median hinge point than in lateral areas. We present a model to explain how alteration of the cell-cycle in the median hinge point could generate wedging of cells in this region.     

Capacity of neural crest cells from various axial levels to participate in thymic development

Summary In order to assess the capacity of neural crest from different sources to participate in thymic development, neural crest from selected axial levels was transplanted unilaterally from quail donors to the region in chick hosts from which neural crest cells normaly migrate to interact with the primordial thymus. The greatest representation of donor cells was observed after isotopic transplantation and when donor tissue was taken from the hyoid and mesencephalic regions of the neural crest. The capacity for transplants to contribute cells decreased both anteriorly and posteriorly, so that neural crest close to the usual origin of mesenchyme-producing cells contributed a larger number of donor cells around the developing thymus than neural crest from anterior and posterior regions. Cells from the transplant were inserted as an addition to the host chick cells. Thus, a special relationship and capacity for interaction in thymic development is expressed by neural crest at usual levels over a limited span of axial regions, but to some extent by all regions. This study has established that the capacity for neural crest cells from different axial levels to interact with developing organs is not uniform, but may vary, depending upon the nature of the interaction with a particular organ.This study was supported by Grant No. 2332, The Council for Tobacco Research, USA, Inc.     

Evidence for the involvement of a SchistoFLRF-amide-like peptide in the neural control of locust oviduct

Summary The presence of a SchistoFLRFamide-like peptide associated with the oviducts of Locusta migratoria has been shown using sequential reversed-phase high performance liquid chromatography separation coupled with radioimmunoassay and bioassay. The peptide is present in areas of the oviduct which receive extensive innervation, with sixfold less peptide in areas that receive little innervation. Material with FMRFamide-like immunoreactivity (determined by radioimmunoassay) is also present in the oviducal nerve and VIIth abdominal ganglion.SchistoFLRFamide is a potent modulator of contraction of this visceral muscle, inhibiting or reducing the amplitude and frequency of spontaneous contractions, relaxing basal tonus, and reducing the amplitude of neurally-evoked, proctolin-induced, glutamate-induced and high potassium-induced contractions. The FMRFamide-like immunoreactivity within the oviducts which co-elutes with SchistoFLRFamide on two separations is also capable of reducing the amplitude of neurally-evoked and proctolin-induced contractions, and of inhibiting spontaneous contractions and relaxing basal tonus.The effects of SchistoFLRFamide upon this visceral muscle are not abolished by the -adrenergic receptor antagonist phentolamine and do not appear to be mediated by cyclic AMP. Thus the receptors for Schisto-FLRFamide are distinct from those of octopamine which mediate similar physiological effects but which are blocked by phentolamine and which are coupled to adenylate cyclase.The results indicate that SchistoFLRFamide, or a very similar peptide, which has previously been identified as a modulator of locust heart beat, is also associated with visceral muscle of the reproductive system, and may play a neural role in concert with octopamine, at modulating muscular activity.Abbreviations BPP Bovine pancreatic polypeptide - BSA Bovine serum albumin - EJP Excitatory junctional potential - FaRPs FMRFamide-related peptides - FLI FMRFamide-like immuno-reactivity - LMS Leucomyosuppressin - RIA Radioimmunoassay - RP-HPLC Reversed-phase high performance liquid chromatography - TFA Trifluoroacetic acid     

The effects of various nutritional supplements on the growth,migration and differentiation ofxenopus laevis neural crest cells in vitro

Summary This study investigates the nutritional requirements ofXenopus laevis neural crest cells and melanophores developing in vitro. A comparison is made between the growth and differentiation of cells in serum-containing medium and a chemically defined, serum-free medium that we have designed. Our chemically defined medium is more efficient than serum-supplemented medium in promoting proliferation of these cells. Several supplements are required to enhance culture development. These include insulin, α-melanocyte stimulating hormone, somatotropin, luteotrophic hormone, linoleic acid, uridine, and putrescine. In addition, collagen and fibronectin provide the most conductive environment tested for cell migration and adhesion. This work was supported by establishment and major equipment grants from the Alberta Heritage Foundation for Medical Research to N. C. M. Nadine C. Milos is a Heritage Medical Research Scholar of the Alberta Heritage Foundation for Medical Research.     

Ganglioside Composition of Normal and Mutant Mouse Embryos

The enrichment of gangliosides in neuronal membranes suggests that they play an important role in CNS development. We recently found a marked tetrasialoganglioside deficiency in twl/twl mutant mouse embryos at embryonic day (E)-11. The recessive twl/twl mutants die at embryonic ages E-9 to E-18 from failed neural differentiation in the ventral portion of the neural tube. In the present study, we examined the composition and distribution of gangliosides in twl/twl mutant mouse embryos at E-12. The total ganglioside sialic acid concentration was significantly lower in the mutants than in normal (+/-) embryos. The mutants also expressed significant deficiencies of gangliosides in the "b" metabolic pathway (GD3, GD1b, GT1b, and GQ1b) and elevations in levels of gangliosides in the "a" metabolic pathway (GM3, GM2, GM1, and GD1a). These findings suggest that the mutants have a partial deficiency in the activity of a specific sialyltransferase in the b pathway. Regional ganglioside distribution was also studied in E-12 normal mouse embryos. The ganglioside composition in heads and bodies was similar to each other and to whole embryos. Total ganglioside concentration and the distribution of b pathway gangliosides were significantly higher in neural tube regions than in nonneural tube regions. These findings suggest that b pathway gangliosides accumulate in differentiating neural cells and that the deficiency of these gangliosides in the twl/twl mutants is closely associated with failed neural differentiation.