Anisotropic growth and large-scale morphogenetic movements contribute to the final size and shape of the adult Drosophila wing. A new study unravels an unexpected contribution of cell death, which ...follows a spatial and temporal pattern, to the growth of the wing and the acquisition of its elongated shape.
The building of fully functional and well-proportioned individuals relies on the precise regulation of the size of each of their constituting organs. A new study unravels a mechanism that confers ...precision to size regulation of the adult Drosophila eye through morphogen-mediated modulation of cell survival.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The developing wing primordium of Drosophila displays a remarkable capacity to regenerate in response to different types of damage. A new study shows that this capacity relies on the activation of a ...pro-regenerative gene regulatory network in two distinct cell populations within the blastema.
The developing wing primordium of Drosophila displays a remarkable capacity to regenerate in response to different types of damage. A new study shows that this capacity relies on the activation of a pro-regenerative gene regulatory network in two distinct cell populations within the blastema.
Building of the Drosophila abdomen relies on the removal of larval cells and expansion, through proliferation, of a population of progenitor epithelial cells. A new study shows that matrix ...metalloproteinases produced by larval cells drive basement membrane degradation and proliferative growth of the progenitor epithelial population.
Building of the Drosophila abdomen relies on the removal of larval cells and expansion, through proliferation, of a population of progenitor epithelial cells. A new study shows that matrix metalloproteinases produced by larval cells drive basement membrane degradation and proliferative growth of the progenitor epithelial population.
The Drosophila wing has served as a paradigm to mechanistically characterize the role of morphogens in patterning and growth. Wingless (Wg) and Decapentaplegic (Dpp) are expressed in two orthogonal ...signaling centers, and their gradients organize patterning by regulating the expression of well-defined target genes. By contrast, graded activity of these morphogens is not an absolute requirement for wing growth. Despite their permissive role in regulating growth, here we show that Wg and Dpp are utilized in a non-interchangeable manner by the two existing orthogonal signaling centers to promote preferential growth along the two different axes of the developing wing. Our data indicate that these morphogens promote anisotropic growth by making use of distinct and non-interchangeable molecular mechanisms. Whereas Dpp drives growth along the anterior-posterior axis by maintaining Brinker levels below a growth-repressing threshold, Wg exerts its action along the proximal-distal axis through a double repression mechanism involving T cell factor (TCF).
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•Wingless promotes tissue growth by restricting the activity of the TCF repressor form•Wingless and Dpp mediate the growth-promoting activities of signaling centers•Morphogens promote growth along distinct axes by using non-interchangeable mechanisms•The range of morphogen gradients and their combined activities regulate final tissue size
Morphogen gradients define the spatial location of patterning structures but are thought to be irrelevant in the regulation of tissue growth. Barrio and Milán show that the Wingless and Decapentaplegic morphogens promote anisotropic growth along the anterior-posterior and proximal-distal axes of the Drosophila wing using distinct and non-interchangeable molecular mechanisms.
Interactions between cells bearing oncogenic mutations and the surrounding microenvironment, and cooperation between clonally distinct cell populations, can contribute to the growth and malignancy of ...epithelial tumors. The genetic techniques available in Drosophila have contributed to identify important roles of the TNF-α ligand Eiger and mitogenic molecules in mediating these interactions during the early steps of tumor formation. Here we unravel the existence of a tumor-intrinsic—and microenvironment-independent—self-reinforcement mechanism that drives tumor initiation and growth in an Eiger-independent manner. This mechanism relies on cell interactions between two functionally distinct cell populations, and we present evidence that these cell populations are not necessarily genetically different. Tumor-specific and cell-autonomous activation of the tumorigenic JNK stress-activated pathway drives the expression of secreted signaling molecules and growth factors to delaminating cells, which nonautonomously promote proliferative growth of the partially transformed epithelial tissue. We present evidence that cross-feeding interactions between delaminating and nondelaminating cells increase each other’s sizes and that these interactions can explain the unlimited growth potential of these tumors. Our results will open avenues toward our molecular understanding of those social cell interactions with a relevant function in tumor initiation in humans.
Developmental transitions, such as puberty or metamorphosis, are tightly controlled by steroid hormones and can be delayed by the appearance of growth abnormalities, developmental tumors, or ...inflammatory disorders such as inflammatory bowel disease or cystic fibrosis.1–4 Here, we used a highly inflammatory epithelial model of malignant transformation in Drosophila5,6 to unravel the role of Upd3—a cytokine with homology to interleukin-6—and the JAK/STAT signaling pathway in coupling inflammation to a delay in metamorphosis. We present evidence that Upd3 produced by malignant and nearby cell populations signals to the prothoracic gland—an endocrine tissue primarily dedicated to the production of the steroid hormone ecdysone—to activate JAK/STAT and bantam microRNA (miRNA) and to delay metamorphosis. Upd cytokines produced by the tumor site contribute to increasing the systemic levels of Upd3 by amplifying its expression levels in a cell-autonomous manner and by inducing Upd3 expression in neighboring tissues in a non-autonomous manner, culminating in a major systemic response to prevent larvae from initiating pupa transition. Our results identify a new regulatory network impacting on ecdysone biosynthesis and provide new insights into the potential role of inflammatory cytokines and the JAK/STAT signaling pathway in coupling inflammation to delays in puberty.
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•Highly inflammatory epithelial tumors cause a strong developmental delay•Upd3 cytokine produced by malignant and nearby cells signals to the prothoracic gland•JAK/STAT signal amplifies the systemic levels of Upd3•JAK/STAT signaling in the ecdysone-producing compartment impacts on the bantam miRNA
Inflammatory tissues cause developmental delay and animal lethality. Romão et al. present evidence that the Upd3 cytokine is produced by inflammatory and adjacent tissues to cause developmental delay by interfering with the production of the hormone ecdysone.
A balanced gene complement is crucial for proper cell function. Aneuploidy, the condition of having an imbalanced chromosome set, alters the stoichiometry of gene copy numbers and protein complexes ...and has dramatic consequences at the cellular and organismal levels. In humans, aneuploidy is associated with different pathological conditions including cancer, microcephaly, mental retardation, miscarriages, and aging. Over the last century, Drosophila has provided a valuable system for studying the consequences of systemic aneuploidies. More recently, it has contributed to the identification and molecular dissection of aneuploidy-induced cellular behaviors and their impact at the tissue and organismal levels. In this perspective, we review this active field of research, first by comparing knowledge from yeast, mouse, and human cells, then by highlighting the contributions of Drosophila. The aim of these discussions was to further our understanding of the functional interplay between aneuploidy, cell physiology, and tissue homeostasis in human development and disease.
During the development of multicellular organisms, body growth is controlled at the scale of the organism by the activity of long-range signaling molecules, mostly hormones. These systemic factors ...coordinate growth between developing tissues and act as relays to adjust body growth in response to environmental changes 1. In target organs, long-range signals act in concert with tissue-autonomous ones to regulate the final size of a given tissue. In Drosophila, the steroid hormone ecdysone plays a dual role: peaks of secretion promote developmental transitions and maturation, while basal production negatively controls the speed of growth. The antagonistic action of ecdysone and the conserved insulin/insulin growth factor (IGF) signaling pathway regulate systemic growth and modulate final body size 2, 3. Here we unravel an unexpected role of bantam microRNA in controlling body size in Drosophila. Our data unveil that, in addition to its well-characterized function in autonomously inducing tissue growth 4–9, bantam activity in ecdysone-producing cells promotes systemic growth by repressing ecdysone release. We also provide evidence that the regulation of ecdysone production by insulin signaling relies on the repression of bantam activity. These results identify a molecular mechanism that underlies the crosstalk between these two hormones and add a new layer of complexity to the well-characterized role of bantam in growth control.
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► bantam is required in ecdysone-producing cells to promote body growth ► bantam inhibits ecdysone biosynthesis ► Insulin signaling regulates ecdysone production by repressing bantam activity ► Both the systemic and tissue-autonomous activities of bantam promote organ growth
The Systemic Control of Growth Boulan, Laura; Milán, Marco; Léopold, Pierre
Cold Spring Harbor perspectives in biology,
12/2015, Letnik:
7, Številka:
12
Journal Article
Recenzirano
Odprti dostop
Growth is a complex process that is intimately linked to the developmental program to form adults with proper size and proportions. Genetics is an important determinant of growth, as exemplified by ...the role of local diffusible molecules setting up organ proportions. In addition, organisms use adaptive responses allowing modulating the size of individuals according to environmental cues, for example, nutrition. Here, we describe some of the physiological principles participating in the determination of final individual size.
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