JAMES TRUMAN

..EH release then facilitates the onset of ecdysis by enhancing the excitability of the CCAP neurons...

..This suppression of embryonic patterning then results in embryonic fields that remain dormant as long as JH is present. These are the primordia that can transform into imaginal discs once JH disappears in preparation for metamorphosis...

..This proposal has general implications for insect developmental biology...

..We discuss how complete metamorphosis may have influenced the molecular aspects of both ecdysone and JH signaling...

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..This paper provides an overall view of the initial connections that eventually lead to the complex connectivity of the bulk of the thoracic neurons...

..The expansion of specific thoracic lineages was accompanied by the reduction of the terminal abdominal lineages as flying insects began to de-emphasize their cercal sensory system...

..The midline glial may play a role during CNS metamorphosis similar to that of their progenitors in the embryo, in stabilizing outgrowing neurites that cross or run along the midline...

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..These observations support the hypothesis that different EcR isoforms control cell-type-specific responses during remodeling of the nervous system at metamorphosis...

..The heterogeneity of EcR expression at the start of metamorphosis presumably reflects the diverse origins and requirements of the neurons that nevertheless are all exposed to a common hormonal signal...

..We suggest that cGMP plays a role in, or reflects, the early stages of communication between a target and specific innervating neurons...

..The disruptive effects of L-NAME were prevented with the addition of 8-bromo-cGMP. These results suggest NO and cGMP act to stabilize retinal growth cones at the start of synaptic assembly...

..Finally, we found that the appearance of sensitivity to EH for triggering the cGMP response coincided with the time at which EH first triggers ecdysis...

..The correlation of a unique pattern of receptor isoform expression with a particular steroid-regulated fate suggests that variations in the pattern of receptor isoform expression may serve as important switches during development...

..The knockouts lacked the lights-on eclosion response despite having a normal circadian eclosion rhythm. This study represents a novel approach to the dissection of neuropeptide regulation of a complex behavioral program...

..These cells show massive depletion of immunoreactive EH at ecdysis...

..These properties of the da system likely allow insects to discriminate the quality and location of several types of stimuli acting on the cuticle...

..A waning in the inhibition eventually allows ecdysis to begin 30-40 min later...

..Unilateral axotomy blocks proliferation within the rudiment, but it does not block its subsequent differentiation into a very thin muscle in the adult...

..This suggests that the NO-cGMP pathway may interact with other biochemical cascades to partition rhythmic motor output from the ganglion...

..The potential relationship between hormone-induced transcriptional change and the calcium dynamics in dendritic morphogenesis is discussed...

..Thus, ecdysteroid and juvenile hormone collaborate to determine the size and shape of the adult musculature...

..We propose that diminished sGC activity in the visual system during development causes inappropriate or inadequate formation of first-order retinal synapses, leading to defects in visual system function and visually mediated behavior...

..The consequence of these opposing pathways is a sharpening of the responsiveness to the steroid, thereby facilitating a tight coordination between development of the different elements of the adult visual system...

..Our observations suggest that silencing by the unliganded EcR/USP receptor and the subsequent release of silencing by moderate steroid levels may play an important role in coordinating early phases of steroid driven development...

..Cyclic GMP is detected primarily in the cytoplasm of plexus neurons and extends into the finest peripheral dendrites. Our results suggest that cGMP participates in the development and/or physiology of this peripheral neural plexus...

..This capacity to regulate distinct phases of development by different concentrations of a single hormone is probably achieved by differential sensitivity of target gene promoters to induction by the hormone-bound receptor(s)...

..Initially, moderate levels of ecdysteroid stimulate proliferation. Later, high levels of 20-hydroxyecdysone trigger a wave of apoptosis within the anlage that marks completion of its proliferative phase...

..Neuroblasts become determined to adopt a male or female state at the end of the first larval instar, a time when abdominal neuroblasts enter their first postembryonic S-phase...

..The results of these manipulations are consistent with the hypothesis that cGMP may partially increase excitability in Cell 27 by enhancing an inward Ca2+ current...

..Comparative studies on other insects indicate that the association between an NO-sensitive guanylate cyclase and synaptogenesis is an ancient one, as evidenced by its presence in both ancient and more recently evolved insect groups...

..The results suggest that local steroid treatments that result in local muscle degeneration bring about a loss of synaptic contacts from regions of muscle degeneration...

..5. Antidromic stimulation of the proctodeal nerve stumps following proctodeal nerve removal triggered precocious ecdysis. This result further supports the conclusion that centrally released EH is sufficient to trigger the motor program...

..These results indicate that although the DGluR-II gene is expressed in somatic muscle cells it is not selectively expressed in nuclei near the synaptic site...

..We speculate that its underlying neural circuitry is conserved through development and later modulated to produce the novel ecdysis pattern expressed in the adult stage...

..In this way, the ecdysone signal can function as a developmental timer coordinating development within the imaginal disc...

..These results are consistent with the role of activation versus derepression via EcR for successive phases of neuronal remodeling and suggest that functional ecdysone receptor is necessary for some, but not all, remodeling events...

..After this shift in br expression, the progressive changes that occur within the nymphal series in basal insects became compressed to the one short period of morphogenesis seen in the larva-to-pupa transition of holometabolous insects...

..Finally, we find that phagocytic blood cells not only engulf neuronal debris but also attack and sever intact branches that show signs of destabilization...

..A new genetically encoded caspase probe revealed that caspase activity is confined to the degenerating dendrites of pruning neurons...

..In addition, we find that, during the adult leg development, some cells in the leg express the patterning genes de novo suggesting that the remodeling of the leg involves changes in the patterning gene regulation...

..Altogether, these data reveal a fundamental pattern of Delta expression that is indicative of an underlying developmental program that confers identity to adult lineage neurons...

..Our findings show that the br isoform functions are broadly conserved within the Holometabola and suggest that evolution of br isoform expression may have played an important role in the evolution of the pupa in holometabolous insects...

..We present evidence that in Drosophila, a component of the ring gland, the prothoracic gland (PG), assesses growth to determine when critical weight has been achieved...

..Instead, creation of the late-forming imaginal discs in Manduca appears to be controlled by unidentified endocrine factors whose activation is regulated by the nutritional state of the animal...

..CO(2) therefore appears to be a novel and non-invasive tool for studies of ecdysis behavior in insects...

..The differing profiles of TIM and PER nuclear accumulation suggest that PER and TIM have distinct functions in the nuclei of vLNs...

..A set of decapitation experiments utilizing rickets mutants and flies that lack cells containing the neuropeptide eclosion hormone, reveals a multicomponent control to the activation of this behavioral program...

..Thus, MsE74B appears to have a similar role at the onset of metamorphosis in Manduca as it does in Drosophila, whereas MsE74A is regulated differently at pupation in Manduca than at pupariation in Drosophila...

..EcR-B1 or EcR-B2 over-expression had little or no effect...

..With later JHm treatments, extension programs appear normal, but retraction programs are maintained beyond their normal time. The JH treatments show the importance of retraction programs in establishing the overall arbor shape...

..Overexpression of each of the BR isoforms caused degeneration of the PG cells but on different time courses, indicating that BR is a signal for the degeneration of the PG cells that normally occurs during the pupal-adult transition...

..We manipulated LD cycles to assess the effects of altered day length on PER and TIM dynamics in clock cells within the central brain as well as light-induced resetting of locomotor rhythms...

..The second population consists of polymorphic cells that contribute to the larval, pupal and adult leg epidermis...

..The LOn signal does not influence the latency of wing spreading, an EH-regulated post-ecdysis behavior...

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..It is the first member of the cystine knot family to have a defined function in invertebrates. Mutants show that the spectrum of bursicon actions is broader than formerly demonstrated...

..Understanding these issues is fundamental to normal brain development and for using stem cells to repair brain disease. ..

..5) Utilize a neuron-myoblast coculture system to examine how neurons are able to direct the type of EcR isoform expressed in embryonic muscle and how receptor isoform choice relates to muscle growth and maturation responses. ..

..Understanding these issues is fundamental to normal brain development and for using stem cells to repair brain disease. ..

..5) Use EcR dominant-negative mutations to selectively suppress cytodynamic modules to establish the role of each on growth dynamics and on the final form of the arbor. ..

..The neural circuitry involved in behaviors that are influenced by the hormone will be studied. Attempts will be made to relate the hormone induced changes in the target cells to this circuitry...

..The impact of altering proliferation patterns on the differentiation of the optic lobes will be determined. ..

..4) Use juvenile hormone treatments to try to redirect EcR expression and to modify the pattern of ecdysone responsive gene expression. The latter will then be related to the effects of such treatments on neuronal responses. ..

..5.) To begin an examination of the relationship of EcR expression to the activation of "early" genes that mediate ecdysteroid action...

..Specific lineage groups will be cultured and their differentiation in vitro in response to steroids will be compared to their normal fate in vivo...