ABA and sugar interactions regulating development: cross-talk or voices in a crowd?

Plant growth and development are controlled by the concerted action of many signaling pathways that integrate information from environmental signals with that from developmental and metabolic cues. Physiological studies have demonstrated that abscisic acid and sugars have both similar and antagonistic effects on diverse processes, including seed development, germination, and seedling growth. Recent genetic studies have identified several loci that are involved in both sugar and hormonal responses. It is rarely clear whether these apparent linkages reflect direct or indirect interactions between sugar and hormone signaling pathways, but the identification of gene products that are encoded at these loci is allowing these possibilities to be tested.     

Mammal pollinators lured by the scent of a parasitic plant

To communicate with animals, plants use signals that are distinct from their surroundings. Animals generally learn to use these signals through associative conditioning; however, signals are most effective when they elicit innate behavioural responses. Many plant species have flowers specialized for pollination by ground-dwelling mammals, but the signals used to attract these pollinators have not been elucidated. Here, we demonstrate the chemical basis for attraction of mammal pollinators to flowers of the dioecious parasitic plant Cytinus visseri (Cytinaceae). Two aliphatic ketones dominate the scent of this species; 3-hexanone, which elicits strong innate attraction in rodents, and 1-hexen-3-one, which repels them in isolation, but not in combination with 3-hexanone. The aliphatic ketone-dominated scent of C. visseri contrasts with those of insect-pollinated plants, which are typically dominated by terpenoids, aromatic or non-ketone aliphatic compounds. 3-hexanone is also known from some bat-pollinated species, suggesting independent evolution of plant signals in derived, highly specialized mammal-pollination systems.     

Hormones and acoustic communication in anuran amphibians

Circulating hormone levels can mediate changes in the quality of courtship signals by males and/or mate choice by females and may thus play an important role in the evolution of courtship signals. Costs associated with shifts in hormone levels of males, for example, could effectively stabilize directional selection by females on male signals. Alternatively, if hormone levels affect the selection of mates by females, then variation in hormone levels among females could contribute to the maintenance of variability in the quality of males' signals. Here, I review what is known regarding the effects of hormone levels on the quality of acoustic signals produced by males and on the choice of mates by females in anuran amphibians. Surprisingly, despite the long history of anuran amphibians as model organisms for studying acoustic communication and physiology, we know very little about how variation in circulating hormone levels contributes to variation in the vocal quality of males. Proposed relationships between androgen levels and vocal quality depicted in recent models, for example, are subject to the same criticisms raised for similar models proposed in relation to birds, namely that the evidence for graded effects of androgens on vocal performance is often weak or not rigorously tested and responses seen in one species are often not observed in other species. Although several studies offer intriguing support for graded effects of hormones on calling behavior, additional comparative studies will be required to understand these relationships. Recent studies indicate that hormones may also mediate changes in anuran females' choice of mates, suggesting that the hormone levels of females can influence the evolution of males' mating signals. No studies to date have concurrently addressed the potential complexity of hormone-behavior relationships from the perspective of sender as well as receiver, nor have any studies addressed the costs that are potentially associated with changes in circulating hormone levels in anurans (i.e., life-history tradeoffs associated with elevations in circulating androgens in males). The mechanisms involved in hormonally induced changes in signal production and selectivity also require further investigation. Anuran amphibians are, in many ways, conducive to investigating such questions.     

A modular library of small molecule signals regulates social behaviors in Caenorhabditis elegans

The nematode C. elegans is an important model for the study of social behaviors. Recent investigations have shown that a family of small molecule signals, the ascarosides, controls population density sensing and mating behavior. However, despite extensive studies of C. elegans aggregation behaviors, no intraspecific signals promoting attraction or aggregation of wild-type hermaphrodites have been identified. Using comparative metabolomics, we show that the known ascarosides are accompanied by a series of derivatives featuring a tryptophan-derived indole moiety. Behavioral assays demonstrate that these indole ascarosides serve as potent intraspecific attraction and aggregation signals for hermaphrodites, in contrast to ascarosides lacking the indole group, which are repulsive. Hermaphrodite attraction to indole ascarosides depends on the ASK amphid sensory neurons. Downstream of the ASK sensory neuron, the interneuron AIA is required for mediating attraction to indole ascarosides instead of the RMG interneurons, which previous studies have shown to integrate attraction and aggregation signals from ASK and other sensory neurons. The role of the RMG interneuron in mediating aggregation and attraction is thought to depend on the neuropeptide Y-like receptor NPR-1, because solitary and social C. elegans strains are distinguished by different npr-1 variants. We show that indole ascarosides promote attraction and aggregation in both solitary and social C. elegans strains. The identification of indole ascarosides as aggregation signals reveals unexpected complexity of social signaling in C. elegans, which appears to be based on a modular library of ascarosides integrating building blocks derived from lipid β-oxidation and amino-acid metabolism. Variation of modules results in strongly altered signaling content, as addition of a tryptophan-derived indole unit to repellent ascarosides produces strongly attractive indole ascarosides. Our findings show that the library of ascarosides represents a highly developed chemical language integrating different neurophysiological pathways to mediate social communication in C. elegans.     

THE CHEMICAL REGULATION OF THE DORMANCY PHASES OF BUD DEVELOPMENT

literature pertaining to the development and regulation of dormancy in the buds of woody species is reviewed and interpreted as follows. Morphological observations, the effects of environmental factors, and other evidence support the concept that bud dormancy involves a cycle of 3 separate phases of development. Beginning at the developmental pattern of spring, the 3 phases are: (1) dormancy development leading to the dormant state; (2) release from dormancy leading to the non-dormant state; and (3) the initiation of spring burst leading again to spring development. The regulation of dormancy is, therefore, discussed in terms of the regulation of development of the apex within each phase and the regulation of transitions between phases. The principal existing theory of dormancy regulation implies that dormancy consists, in total, of merely the inhibition of spring development, and that regulation involves first the accumulation of an inhibitor then its disappearance. The conceptual basis of this inhibitor theory is argued to be inadequate as is the experimental evidence for the existence of a specific inhibitor and for a correlation between its concentration and dormancy induction or release. There is little direct evidence on the mechanism of the regulation of bud development within any developmental phase. Circumstantial evidence suggests the developmental patterns arise from chemical patterns resulting from the interactions of classes of growth regulator such as auxin, kinin, and gibberellin. Some evidence exists concerning the regulation of the transitions between the phases of dormancy. A substance has recently been detected which may be a hormone regulating the initiation of dormancy development. The production of this substance may be photoperiodically determined. A role for gibberellins in the regulation of dormancy release has been postulated.     

TAA1-mediated auxin biosynthesis is essential for hormone crosstalk and plant development

Plants have evolved a tremendous ability to respond to environmental changes by adapting their growth and development. The interaction between hormonal and developmental signals is a critical mechanism in the generation of this enormous plasticity. A good example is the response to the hormone ethylene that depends on tissue type, developmental stage, and environmental conditions. By characterizing the Arabidopsis wei8 mutant, we have found that a small family of genes mediates tissue-specific responses to ethylene. Biochemical studies revealed that WEI8 encodes a long-anticipated tryptophan aminotransferase, TAA1, in the essential, yet genetically uncharacterized, indole-3-pyruvic acid (IPA) branch of the auxin biosynthetic pathway. Analysis of TAA1 and its paralogues revealed a link between local auxin production, tissue-specific ethylene effects, and organ development. Thus, the IPA route of auxin production is key to generating robust auxin gradients in response to environmental and developmental cues.     

Developmental delay and unstable state of the testes in the rdw rat with congenital hypothyroidism

From the present study of the rdw rat, it is clear that the thyroid hormone is essential for the development and maintenance of the testes. In previous studies, the thyroid hormone has few serious effects on the testes except during the neonatal stage when the thyroid hormone receptor is mainly present. However, there is little knowledge concerning the prolonged effect of thyroid hormone deficiency throughout the rat's life span. In the present study, a morphological analysis was performed on the testes of rdw rats with congenital hypothyroidism. The rdw testes required a longer time to develop into the normal adult structure. Moreover, the developed, normal structure began to degenerate after full maturation. Specific characteristics of the rdw testes include: (i) a prolonged proliferation of Sertoli cells during postnatal development; (ii) a developmental delay in the appearance of spermatocytes and spermatid; (iii) direct contact with each other for both spermatocytes and spermatids, without Sertoli cell cytoplasm completely intervening between adjacent germ cells; (iv) subsequent apoptosis of germ cells after maturation; (v) reduction in the height of the seminiferous epithelium; and (vi) lower testosterone levels in the rdw rats, especially during old age. Thus, we conclude that the thyroid hormone plays an important role in developing and maintaining normal function of testes.     

Sex Steroid Hormone Levels and Reproductive Development of Eight-Year-Old Children following In Utero and Environmental Exposure to Phthalates

In utero exposure to phthalates may adversely affect reproductive development in children due to the anti-androgenic properties of the pthalates. Accordingly, we aimed to determine the effects of in utero and environmental phthalate exposure on the reproductive development of eight-year-old children. We recruited 180 children in central Taiwan during November 2001 and followed them until August 2009 when all children became eight years old. Birth outcomes were collected. Bone age, hormone concentrations, and reproductive developmental stages were determined. Phthalate metabolite levels, including mono-2-ethylhexyl phthalate [MEHP], mono-n-butyl phthalate [MnBP], and mono-benzyl phthalate [MBzP], were assessed. No significant gender differences were found in in utero phthalate exposure. Maternal urinary levels of phthalate metabolites did not correlate significantly with birth outcomes, physical characteristics, and reproductive hormones of the eight-year-old children. Regarding the urinary phthalate metabolite levels of the eight-year-old children, MEHP correlated significantly with serum progesterone levels. MEHP levels in girls correlated significantly with serum progesterone levels. MnBP correlated significantly with serum FSH in all children. In girls, MnBP correlated with serum FSH, and MBzP correlated with serum progesterone and FSH levels. Urinary phthalate metabolite levels did not correlate with female developmental stages or the development of female reproductive organs. Phthalate metabolites did not correlate with the physical characteristics and reproductive hormones in boys. Therefore, environmental exposure to phthalates, as determined by urinary phthalate metabolite levels of eight-year-old children, may affect reproductive hormone levels in children, indicating that further studies on the environmental health effects of phthalates are warranted.     

The ups and downs of signalling between root and shoot

It is becoming increasingly apparent that the long-distance signalling associated with many developmental processes is complex and that novel hormone-like signals may play substantial roles. The past decades have seen several substances (e.g. brassinosteroids, systemin and other polypeptides, mevalonic and jasmonic acids, polyamines, oligosaccharides, flavonoids, and quinones) vie for a place among the classical plant hormones (e.g. Spaink, 1996). Recent microinjection and grafting studies have also shown that RNA may act as a long-distance signal (Jorgensen et al ., 1998; Xoconostle-Cázares et al ., 1999). In this issue, Hannah et al . describe long-distance signalling and the regulation of root–shoot partitioning in dwarf lethal or dosage-dependent lethal ( DL ) mutants of common bean (Shii et al ., 1980, 1981), and present evidence indicating that substances in addition to classical plant hormones (e.g. cytokinins) may be involved.
As in the report by Hannah et al ., much of the evidence for roles of unidentified long-distance signals in the control of plant development is indirect. The possibility that a small number of long-distance signals might control a multitude of developmental processes arises through the potential for differences in tissue sensitivity, fluctuations in hormone levels and differences in the nature of responses of different tissues to the same hormone. Consequently, particular hormones may influence numerous processes seemingly simultaneously, yet independently. Even so, long-distance signalling is involved in processes as diverse as root–shoot balance, senescence, branching, flowering, nodulation, stress responses and nutrient uptake. Through comparison of even a few different developmental processes, progress can be made to reveal the true complexity of plant development. Using this approach it is also clear that many unknown signals may be involved.     

The Concept of Hormesis in Developmental Toxicology

Animal bioassay experiments are frequently conducted to assess the toxicity of chemicals on the developing fetus. Experiments are normally conducted at dosage levels that are much higher than human exposure levels to elicit the toxic reproductive effect of the chemical in a limited number of litters. Recently there has been much discussion on the fact that some chemicals may have beneficial effects at low doses and become toxic at high doses. This concept, known as chemical hormesis, has been the focus of attention in many investigations. Here, we consider the prevalence of hormesis in developmental toxicology and show that current design of developmental toxicity testing does not accommodate the study of hormesis. If it can be proved that some developmental toxicants may have stimulatory low dose effects, then design and analysis of developmental toxicity experiments need to be revised by the scientific community and the regulatory agencies. Using a thorough analysis of an experimental data set, we further demonstrate that in order to establish the possible hormetic effects of a chemical in reproduction, often a multiple replication of the experiment may be necessary to examine such effects. Using a trend test, we illustrate that while it is possible that one replicate of a developmental toxicity experiment with a known teratogen shows strong evidence of hormesis, other replicates may show no sign of beneficial effects at low doses.     

Regulation of auxin transport polarity by AGC kinases

The plant hormone auxin controls plant development through gradients and maxima that are generated by PIN efflux carrier driven polar auxin transport. PIN proteins direct this cell-to-cell auxin transport, and thus orient plant development through their asymmetric subcellular distribution. PIN polarity is regulated by PINOID and the phototropins, members of the AGC protein serine/threonine kinase family. Here we review the signaling pathways of these kinases and the role of calcium and BTB proteins in translating both internal and external signals into developmental responses via PIN relocalization, to adapt plant development to changing environmental conditions.     

Developmentally specific effects of the DNA cross-linking agent mitomycin C on phosphoenolpyruvate carboxykinase gene expression in vivo: Correlation with changes in chromatin structure within the promoter region of the gene

Previous studies in our laboratory have demonstrated that genotoxic chemical carcinogens have strong preferential effects on expression of certain inducible genes at nonovertly toxic doses in vivo. The effects of the DNA cross-linking agent and chemotherapy drug, mitomycin C (MMC), on expression of the developmental and hormone-regulated gene, phosphoenolpyruvate carboxykinase (PEPCK), were examined in chick embryo liver in vivo as a function of development and were compared with changes in the chromatin structure of the PEPCK gene promoter. The liver PEPCK gene was fully hormone inducible as early as 8 days of embryonic development but was refractory to MMC until after day 10. This onset of responsiveness to MMC was correlated with qualitative changes in the pattern of DNase I hypersensitive sites (DHS) within the PEPCK promoter. There was also a gradual decrease and then a complete loss of both hormone inducibility and MMC responsiveness between 14 and 17 days of development that was correlated with a quantitative change in the overall DNase sensitivity of the liver PEPCK gene promoter over this period. These results suggest that carcinogen sensitivity of the PEPCK gene is related to its ability to respond to its normal induction signals and that chromatin structure may play a central role in these effects. © 1998 John Wiley & Sons, Inc. J Biochem Mol Toxicol 12: 325–337, 1998     

Deficiency of prohormone convertase dPC2 (AMONTILLADO) results in impaired production of bioactive neuropeptide hormones in Drosophila

Peptide hormones synthesized by secretory neurons in the CNS are important regulators of physiology, behavior, and development. Like other neuropeptides, they are synthesized from larger precursor molecules by a specific set of enzymes. Using a combination of neurogenetics, immunostainings, and direct mass spectrometric profiling, we show that the presence of Drosophila prohormone convertase 2 encoded by the gene amontillado (amon) is a prerequisite for the proper processing of neuropeptide hormones from the major neurohemal organs of the CNS. A loss of amon correlates with a loss of neuropeptide hormone signals from the larval ring gland and perisympathetic organs. Neuropeptide hormone signals were still detectable in the adult corpora cardiaca of older amon-deficient flies which were amon heat-shock-rescued until eclosion. A semiquantification by direct peptide profiling using stable isotopic standards showed, however, that their neuropeptide hormone levels are strongly reduced. Targeted expression of GFP under the control of amon regulatory regions revealed a co-localization with the investigated peptide hormones in secretory neurons of the brain and ventral nerve cord. The lack of AMON activity resulted in a deficiency of L3 larva to enter the wandering phase. In conclusion, our findings provide the first direct evidence that AMON is a key enzyme in the production of neuropeptides in the fruitfly.     

Developmental effects of ghrelin

Ghrelin is a pleiotropic hormone that was originally described as promoting feeding and stimulating growth hormone release in adults. A growing body of evidence suggests that ghrelin may also exert developmental and organizational effects during perinatal life. The perinatal actions of ghrelin include the regulation of early developmental events such as blastocyst development and perinatal growth. Moreover, alterations in perinatal ghrelin levels result in structural differences in various peripheral organs, such as the pancreas and gastrointestinal tract. Recent data have also suggested that ghrelin acts on appetite-related brain centers in early life. Together, these observations indicate that exposure to factors that alter how ghrelin impacts development may induce lasting effects on physiological regulation.     

The chemical defense ecology of marine unicellular plankton: constraints, mechanisms, and impacts

The activities of unicellular microbes dominate the ecology of the marine environment, but the chemical signals that determine behavioral interactions are poorly known. In particular, chemical signals between microbial predators and prey contribute to food selection or avoidance and to defense, factors that probably affect trophic structure and such large-scale features as algal blooms. Using defense as an example, I consider physical constraints on the transmission of chemical information, and strategies and mechanisms that microbes might use to send chemical signals. Chemical signals in a low Re, viscosity-dominated physical environment are transferred by molecular diffusion and laminar advection, and may be perceived at nanomolar levels or lower. Events that occur on small temporal and physical scales in the "near-field" of prey are likely to play a role in cell-cell interactions. On the basis of cost-benefit optimization and the need for rapid activation, I suggest that microbial defense system strategies might be highly dynamic. These strategies include compartmented and activated reactions, utilizing both pulsed release of dissolved signals and contact-activated signals at the cell surface. Bioluminescence and extrusome discharge are two visible manifestations of rapidly activated microbial defenses that may serve as models for other chemical reactions as yet undetected due to the technical problems of measuring transient chemical gradients around single cells. As an example, I detail an algal dimethylsulfoniopropionate (DMSP) cleavage reaction that appears to deter protozoan feeding and explore it as a possible model for a rapidly activated, short-range chemical defense system. Although the exploration of chemical interactions among planktonic microbes is in its infancy, ecological models from macroorganisms provide useful hints of the complexity likely to be found.     

Cell adhesion and mechanical stimulation in the regulation of mesenchymal stem cell differentiation

Stem cells have been shown to have the potential to provide a source of cells for applications to tissue engineering and organ repair. The mechanisms that regulate stem cell fate, however, mostly remain unclear. Mesenchymal stem cells (MSCs) are multipotent progenitor cells that are isolated from bone marrow and other adult tissues, and can be differentiated into multiple cell lineages, such as bone, cartilage, fat, muscles and neurons. Although previous studies have focused intensively on the effects of chemical signals that regulate MSC commitment, the effects of physical/mechanical cues of the microenvironment on MSC fate determination have long been neglected. However, several studies provided evidence that mechanical signals, both direct and indirect, played important roles in regulating a stem cell fate. In this review, we summarize a number of recent studies on how cell adhesion and mechanical cues influence the differentiation of MSCs into specific lineages. Understanding how chemical and mechanical cues in the microenvironment orchestrate stem cell differentiation may provide new insights into ways to improve our techniques in cell therapy and organ repair.