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J C Weeks

Publications and source records attributed to J C Weeks.

99 records · Page 6Linked to original sources

Time course of hormonal independence for developmental events in neurons and other cell types during insect metamorphosis.

The ecdysteroid dependence of developmental events during the larval-pupal transformation of the tobacco hornworm, Manduca sexta, was studied using the technique of abdomen ligation to eliminate the ecdysteroid-secreting prothoracic glands (PTG) in the thorax. The time at which a particular developmental event no longer required the presence of the PTG for its successful completion, i.e., when the event became ecdysteroid independent, was determined for the dendritic regression and death of proleg motor neuron PPR, the degeneration of its target muscle PPRM, and the secretion of pupal cuticle by the abdominal epidermis. Groups of abdomens were ligated from synchronously developing larvae at 12-hr intervals over the 4-day period preceding entry into the pupal stage. PPR's dendritic regression became ecdysteroid independent over the first 24 hr of this period. When abdomens were ligated midway through this period PPR became arrested in a partially regressed state. Twelve hours after PPR's regression became independent, the degeneration of PPRM and the secretion of pupal cuticle by the epidermis acquired independence. Another 12 hr elapsed before PPR's programmed death became independent. Thus, different developmental events acquired ecdysteroid independence in a stereotyped temporal sequence, and even different events within a single cell, i.e., PPR's regression and death, became independent at different times.

Abdomen↗

Steroid control of neuron and muscle development during the metamorphosis of an insect.

Insect metamorphosis is controlled by a small ensemble of developmental hormones including a class of steroids--the ecdysteroids. In the tobacco hornworm, Manduca sexta, the progression from the larval to pupal to adult stages is controlled by the relative blood titers of ecdysteroids and juvenile hormone (JH). The cellular events in the nervous and muscular systems which accompany metamorphosis resemble those of embryonic development, but they occur in an animal which is larger and experimentally more tractable than an embryo. In this paper we review the role of ecdysteroids in directing the metamorphosis of the nervous and muscular systems in Manduca, and how JH modifies the cellular responses to the steroids. In particular, we describe how these hormones control muscle degeneration, changes in the structure and function of identified neurons, and programmed neuron death. One general finding is that interactions between cells (e.g., neurons and their target muscles) are not involved in their hormonal responses, but rather the hormones act independently and in parallel at the different sites. Another key finding is that the critical periods and hormonal requirements for the commitment to a particular differentiative pathway, and the phenotypic expression of that pathway, can differ, and are therefore experimentally separable. Finally, we find that the significance of a hormonal signal (e.g., a rise in blood ecdysteroids) is interpreted differently depending upon the previous history of hormone exposure of a neuron or muscle. This progressive change in the interpretation of hormonal signals is a major mechanism by which a limited number of hormones can orchestrate a complicated phenomenon such as metamorphosis.

Aging↗

Hormonally mediated reprogramming of muscles and motoneurones during the larval-pupal transformation of the tobacco hornworm, Manduca sexta.

The larval-pupal transformation of Manduca sexta results from an exposure to ecdysteroids in the absence of juvenile hormone (the commitment pulse), followed by a larger exposure to ecdysteroids (the prepupal peak) with a reappearance of juvenile hormone (JH). The prepupal ecdysteroid peak triggers the degeneration of abdominal muscles, and the dendritic regression and death of identified motoneurones. The present experiments examined the role of the commitment pulse in the larval-pupal reprogramming of these cells. The commitment pulse did not overtly affect the muscles and motoneurones, but it switched their hormonal responsiveness; before the commitment pulse, exposure to ecdysteroids in the presence of JH had no effect on the larval cells, whereas after the commitment pulse the same treatment caused regression and death. Thus, JH lost its ability to prevent pupal development. Furthermore, treatment with ecdysteroids in the absence of JH before the commitment pulse promoted pupal development much less effectively than did the same treatment given after the commitment pulse, indicating that the commitment pulse facilitates the subsequent responsiveness to ecdysteroids. Thus, the commitment pulse covertly causes both qualitative and quantitative changes in the hormonal sensitivity of the larval muscles and motoneurones.

Animals↗

Independent steroid control of the fates of motoneurons and their muscles during insect metamorphosis.

The metamorphosis of insects is controlled by the blood titers of a small number of developmental hormones including a class of steroids, the ecdysteroids. We have studied the developmental fates of several muscles and their motoneurons during the larval-pupal transformation of the tobacco hornworm, Manduca sexta. The endocrine events which trigger pupal development are first, a fall in the blood titer of juvenile hormone, followed by two subsequent elevations of blood ecdysteroids. The small "commitment pulse" of ecdysteroids commits tissues to pupal development, whereas the sustained "prepupal peak" causes the new pupa to be formed (Riddiford, L. M. (1980) In Progress in Ecdysone Research, J.A. Hoffmann, ed., pp. 409-430, Elsevier/North-Holland Biomedical Press, Amsterdam). In the present experiments we were able to correlate specific aspects of the changing blood steroid titers with the degeneration of larval muscles, and with the dendritic regression and death of their motoneurons. The abdominal prolegs, which are the principal locomotory appendages of the caterpillar, are lost during the larval-pupal transformation. We have followed the fates of a proleg retractor muscle, PPRM, and its single motoneuron, PPR. Two other differently fated abdominal muscles not associated with the proleg were also studied. Surgical and endocrinological manipulations showed that PPRM degenerates in response to the rising phase of the prepupal ecdysteroid peak and that interactions with its motoneuron are not involved in the muscle's death. Motoneuron PPR responds to the rising prepupal peak by first reducing its dendritic arbor by 40% and then dying. Other proleg motoneurons regress but do not die, indicating that dendritic regression is programmed separately from neuronal death. Neither the dendritic reduction nor the death of PPR involves interactions with its target muscle. These results indicate that ecdysteroids have independent and parallel effects in the periphery, where they cause muscle degeneration, and in the central nervous system, where they cause dendritic regression and death of motoneurons.

Animals↗

Segmental specialization of a leech swim-initiating interneuron, cell 2051.

The physiological and anatomical properties of an unpaired intersegmental interneuron designated cell 205 are described. Cell 205 is unusual among leech neurons in that it combines a variety of functional properties in a single cell. Constant current depolarization of cell 205 initiates and maintains swimming behavior in semi-intact leeches or the swim motor pattern in brainless, isolated nerve cords. During swim episodes elicited by other stimuli, cell 205 is rhythmically active. Current pulses passed into cell 205 during swimming reset the pattern, indicting that it has access to, or may be a member of, the swim central pattern generator (CPG). Cell 205 is the first interneuron in this system to exhibit both swim-initiating and CPG functions. Individual touch, pressure, and nociceptive primary mechanoreceptor neurons polysynaptically excite cell 205, which, in addition, is coupled electrically to the multimodal S interneuron. These inputs may contribute to the initiation and/or modulation of swimming in response to sensory stimuli. Cell 205 shares some common synaptic inputs and outputs with the only other known swim-initiating interneuron, cell 204, but the two cells differ fundamentally in that cell 204 exerts only a tonic effect on the CPG. No synaptic interactions were found between cells 204 and 205, but their excitatory effects on swimming summate. Unlike other swim neurons which are segmentally repeated, cell 205 generally is present only in segment 9, and numerous lines of evidence suggest that it is, in fact, a segmentally differentiated homolog of cell 204.

Animals↗

Comparison of time-tradeoff utilities and rating scale values of cancer patients and their relatives: evidence for a possible plateau relationship.

Because they are easy to administer, rating scales are often used as proxies for utility measures. The authors investigated the relationship between time-tradeoff utilities and rating scale values in two populations: 124 cancer patients asked to evaluate their current states of health and 102 relatives and close friends of cancer patients asked to evaluate health-state scenarios. None of the models tested effectively described the relationship between individual patients' rating scale values and time-tradeoff utilities for their current states of health. In contrast, both a plateau and a power-function model explained the variability in the responses of the relatives reasonably well (R2 = 0.56 and R2 = 0.58, respectively). Given that many respondents who were unwilling to trade off any time assigned rating scale values of well below 100, a plateau model may represent the best approach to adjusting rating scale values for health-state scenarios when it is not feasible to elicit time-tradeoff utilities.

Activities of Daily Living↗