RESUMEN
Understanding the mechanisms governing body size attainment during animal development is of paramount importance in biology. In insects, a crucial phase in determining body size occurs at the larva-pupa transition, marking the end of the larval growth period. Central to this process is the attainment of the threshold size (TS), a critical developmental checkpoint that must be reached before the larva can undergo metamorphosis. However, the intricate molecular mechanisms by which the TS orchestrates this transition remain poor understood. In this study, we investigate the role of the interaction between the Torso and TGFß/activin signaling pathways in regulating metamorphic timing in the red flour beetle, Tribolium castaneum. Our results show that Torso signaling is required specifically during the last larval instar and that its activation is mediated not only by the prothoracicotropic hormone (Tc-Ptth) but also by Trunk (Tc-Trk), another ligand of the Tc-Torso receptor. Interestingly, we show that while Tc-Torso activation by Tc-Ptth determines the onset of metamorphosis, Tc-Trk promotes growth during the last larval stage. In addition, we found that the expression of Tc-torso correlates with the attainment of the TS and the decay of juvenile hormone (JH) levels, at the onset of the last larval instar. Notably, our data reveal that activation of TGFß/activin signaling pathway at the TS is responsible for repressing the JH synthesis and inducing Tc-torso expression, initiating metamorphosis. Altogether, these findings shed light on the pivotal involvement of the Ptth/Trunk/Torso and TGFß/activin signaling pathways as critical regulatory components orchestrating the TS-driven metamorphic initiation, offering valuable insights into the mechanisms underlying body size determination in insects.
Asunto(s)
Proteínas de Insectos , Proteínas Tirosina Quinasas Receptoras , Tribolium , Animales , Regulación del Desarrollo de la Expresión Génica , Proteínas de Insectos/genética , Proteínas de Insectos/metabolismo , Hormonas Juveniles/genética , Hormonas Juveniles/metabolismo , Larva/metabolismo , Metamorfosis Biológica , Tribolium/crecimiento & desarrollo , Tribolium/metabolismo , Proteínas Tirosina Quinasas Receptoras/metabolismoRESUMEN
Several transcription factors have been identified that activate an epithelial-to-mesenchymal transition (EMT), which endows cells with the capacity to break through basement membranes and migrate away from their site of origin. A key program in development, in recent years it has been shown to be a crucial driver of tumour invasion and metastasis. However, several of these EMT-inducing transcription factors are often expressed long before the initiation of the invasion-metastasis cascade as well as in non-invasive tumours. Increasing evidence suggests that they may promote primary tumour growth, but their precise role in this process remains to be elucidated. To investigate this issue we have focused our studies on two Drosophila transcription factors, the classic EMT inducer Snail and the Drosophila orthologue of hGATAs4/6, Serpent, which drives an alternative mechanism of EMT; both Snail and GATA are specifically expressed in a number of human cancers, particularly at the invasive front and in metastasis. Thus, we recreated conditions of Snail and of Serpent high expression in the fly imaginal wing disc and analysed their effect. While either Snail or Serpent induced a profound loss of epithelial polarity and tissue organisation, Serpent but not Snail also induced an increase in the size of wing discs. Furthermore, the Serpent-induced tumour-like tissues were able to grow extensively when transplanted into the abdomen of adult hosts. We found the differences between Snail and Serpent to correlate with the genetic program they elicit; while activation of either results in an increase in the expression of Yorki target genes, Serpent additionally activates the Ras signalling pathway. These results provide insight into how transcription factors that induce EMT can also promote primary tumour growth, and how in some cases such as GATA factors a 'multi hit' effect may be achieved through the aberrant activation of just a single gene.
Asunto(s)
Proliferación Celular/genética , Proteínas de Drosophila/fisiología , Drosophila/genética , Transición Epitelial-Mesenquimal/genética , Factores de Transcripción GATA/fisiología , Neoplasias/patología , Factores de Transcripción de la Familia Snail/fisiología , Animales , Animales Modificados Genéticamente , Línea Celular Tumoral , Drosophila/embriología , Drosophila/crecimiento & desarrollo , Drosophila/fisiología , Proteínas de Drosophila/genética , Embrión no Mamífero , Femenino , Factores de Transcripción GATA/genética , Invasividad Neoplásica , Neoplasias/genética , Factores de Transcripción de la Familia Snail/genética , Factores de Transcripción/genética , Factores de Transcripción/fisiología , Carga Tumoral/genética , Alas de Animales/embriología , Alas de Animales/trasplanteRESUMEN
It is not clear how simple genetic changes can account for the coordinated variations that give rise to modified functional organs. Here, we addressed this issue by analysing the expression and function of regulatory genes in the developing tracheal systems of two insect species. The larval tracheal system of Drosophila can be distinguished from the less derived tracheal system of the beetle Tribolium by two main features. First, Tribolium has lateral spiracles connecting the trachea to the exterior in each segment, while Drosophila has only one pair of posterior spiracles. Second, Drosophila, but not Tribolium, has two prominent longitudinal branches that distribute air from the posterior spiracles. Both innovations, while considered different structures, are functionally dependent on each other and linked to habitat occupancy. We show that changes in the domains of spalt and cut expression in the embryo are associated with the acquisition of each structure. Moreover, we show that these two genetic modifications are connected both functionally and genetically, thus providing an evolutionary scenario by which a genetic event contributes to the joint evolution of functionally inter-related structures.
Asunto(s)
Morfogénesis/fisiología , Tráquea/metabolismo , Tribolium/metabolismo , Animales , Drosophila/metabolismo , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Proteínas de Homeodominio/genética , Proteínas de Homeodominio/metabolismo , Proteínas de Insectos/genética , Proteínas de Insectos/metabolismo , Morfogénesis/genética , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Transducción de Señal/genética , Transducción de Señal/fisiología , Factores de Transcripción/genética , Factores de Transcripción/metabolismoRESUMEN
Complete metamorphosis (Holometaboly) is a key innovation that underlies the spectacular success of holometabolous insects. Phylogenetic analyses indicate that Holometabola form a monophyletic group that evolved from ancestors exhibiting hemimetabolous development (Hemimetaboly). However, the nature of the changes underlying this crucial transition, including the occurrence of the holometabolan-specific pupal stage, is poorly understood. Using the holometabolous beetle Tribolium castaneum as a model insect, here we show that the transient up-regulation of the anti-metamorphic Krüppel-homolog 1 (TcKr-h1) gene at the end of the last larval instar is critical in the formation of the pupa. We find that depletion of this specific TcKr-h1 peak leads to the precocious up-regulation of the adult-specifier factor TcE93 and, hence, to a direct transformation of the larva into the adult form, bypassing the pupal stage. Moreover, we also find that the TcKr-h1-dependent repression of TcE93 is critical to allow the strong up-regulation of Broad-complex (TcBr-C), a key transcription factor that regulates the correct formation of the pupa in holometabolous insects. Notably, we show that the genetic interaction between Kr-h1 and E93 is also present in the penultimate nymphal instar of the hemimetabolous insect Blattella germanica, suggesting that the evolution of the pupa has been facilitated by the co-option of regulatory mechanisms present in hemimetabolan metamorphosis. Our findings, therefore, contribute to the molecular understanding of insect metamorphosis, and indicate the evolutionary conservation of the genetic circuitry that controls hemimetabolan and holometabolan metamorphosis, thereby shedding light on the evolution of complete metamorphosis.
Asunto(s)
Evolución Molecular , Metamorfosis Biológica/genética , Filogenia , Tribolium/genética , Animales , Dominio BTB-POZ/genética , Blattellidae/genética , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Regulación del Desarrollo de la Expresión Génica , Factores de Transcripción de Tipo Kruppel/genética , Factores de Transcripción de Tipo Kruppel/metabolismo , Larva/genética , Larva/crecimiento & desarrollo , Pupa/genética , Pupa/crecimiento & desarrollo , Interferencia de ARN , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Tribolium/crecimiento & desarrolloRESUMEN
All immature animals undergo remarkable morphological and physiological changes to become mature adults. In winged insects, metamorphic changes either are limited to a few tissues (hemimetaboly) or involve a complete reorganization of most tissues and organs (holometaboly). Despite the differences, the genetic switch between immature and adult forms in both types of insects relies on the disappearance of the antimetamorphic juvenile hormone (JH) and the transcription factors Krüppel-homolog 1 (Kr-h1) and Broad-Complex (BR-C) during the last juvenile instar. Here, we show that the transcription factor E93 is the key determinant that promotes adult metamorphosis in both hemimetabolous and holometabolous insects, thus acting as the universal adult specifier. In the hemimetabolous insect Blattella germanica, BgE93 is highly expressed in metamorphic tissues, and RNA interference (RNAi)-mediated knockdown of BgE93 in the nymphal stage prevented the nymphal-adult transition, inducing endless reiteration of nymphal development, even in the absence of JH. We also find that BgE93 down-regulated BgKr-h1 and BgBR-C expression during the last nymphal instar of B. germanica, a key step necessary for proper adult differentiation. This essential role of E93 is conserved in holometabolous insects as TcE93 RNAi in Tribolium castaneum prevented pupal-adult transition and produced a supernumerary second pupa. In this beetle, TcE93 also represses expression of TcKr-h1 and TcBR-C during the pupal stage. Similar results were obtained in the more derived holometabolous insect Drosophila melanogaster, suggesting that winged insects use the same regulatory mechanism to promote adult metamorphosis. This study provides an important insight into the understanding of the molecular basis of adult metamorphosis.
Asunto(s)
Blattellidae/fisiología , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/fisiología , Metamorfosis Biológica/genética , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Tribolium/fisiología , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Evolución Biológica , Blattellidae/genética , Blattellidae/crecimiento & desarrollo , Drosophila melanogaster/genética , Drosophila melanogaster/crecimiento & desarrollo , Regulación del Desarrollo de la Expresión Génica/efectos de los fármacos , Proteínas de Insectos/genética , Proteínas de Insectos/metabolismo , Hormonas Juveniles/genética , Hormonas Juveniles/metabolismo , Factores de Transcripción de Tipo Kruppel/metabolismo , Larva/genética , Larva/crecimiento & desarrollo , Larva/fisiología , Metamorfosis Biológica/efectos de los fármacos , Metopreno/farmacología , Datos de Secuencia Molecular , Especificidad de la Especie , Tribolium/genética , Tribolium/crecimiento & desarrolloRESUMEN
Genetic screens in the yeast Saccharomyces cerevisiae have identified many proteins involved in the secretory pathway, most of which have orthologues in higher eukaryotes. To investigate whether there are additional proteins that are required for secretion in metazoans but are absent from yeast, we used genome-wide RNA interference (RNAi) to look for genes required for secretion of recombinant luciferase from Drosophila S2 cells. This identified two novel components of the secretory pathway that are conserved from humans to plants. Gryzun is distantly related to, but distinct from, the Trs130 subunit of the TRAPP complex but is absent from S. cerevisiae. RNAi of human Gryzun (C4orf41) blocks Golgi exit. Kish is a small membrane protein with a previously uncharacterised orthologue in yeast. The screen also identified Drosophila orthologues of almost 60% of the yeast genes essential for secretion. Given this coverage, the small number of novel components suggests that contrary to previous indications the number of essential core components of the secretory pathway is not much greater in metazoans than in yeasts.
Asunto(s)
Proteínas de Drosophila/genética , Drosophila/genética , Genes de Insecto , Vías Secretoras , Animales , Línea Celular , Drosophila/metabolismo , Proteínas de Drosophila/metabolismo , Eucariontes/genética , Eucariontes/metabolismo , Aparato de Golgi/metabolismo , Humanos , Interferencia de ARN , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismoRESUMEN
Regulation of gene expression is arguably the main mechanism underlying the phenotypic diversity of tissues within and between species. Here we assembled an extensive transcriptomic dataset covering 8 tissues across 20 bilaterian species and performed analyses using a symmetric phylogeny that allowed the combined and parallel investigation of gene expression evolution between vertebrates and insects. We specifically focused on widely conserved ancestral genes, identifying strong cores of pan-bilaterian tissue-specific genes and even larger groups that diverged to define vertebrate and insect tissues. Systematic inferences of tissue-specificity gains and losses show that nearly half of all ancestral genes have been recruited into tissue-specific transcriptomes. This occurred during both ancient and, especially, recent bilaterian evolution, with several gains being associated with the emergence of unique phenotypes (for example, novel cell types). Such pervasive evolution of tissue specificity was linked to gene duplication coupled with expression specialization of one of the copies, revealing an unappreciated prolonged effect of whole-genome duplications on recent vertebrate evolution.
Asunto(s)
Evolución Molecular , Insectos , Vertebrados , Animales , Insectos/genética , Vertebrados/genética , Especificidad de Órganos , Transcriptoma , FilogeniaRESUMEN
The role of steroid hormone signaling during insect post-embryonic development has been extensively characterized. However, its function during embryonic development is less understood, particularly in short-germ band hemimetabolous insects. To solve this, we have used Blattella germanica to analyze the embryonic functions of the heterodimeric ecdysone receptor, BgEcR-A and BgRXR. Here, we show that both transcripts are present from the beginning of embryogenesis, and that are required for proper germband formation. We also show that they regulate an early induction of a stereotypical cascade of nuclear receptors. Notably, we found that one of these, BgHR3, controls the formation of the cephalic region of the germband. Finally, spatial expression of two other receptors, BgE75-A and BgFTZ-F1, suggest their involvement in the formation of the nervous system and in germband segmentation, respectively. In summary, our results highlight the critical roles of ecdysone-signaling during early embryogenesis in short-germ band hemimetabolous insects.
RESUMEN
During development, the growing organism transits through a series of temporally regulated morphological stages to generate the adult form. In humans, for example, development progresses from childhood through to puberty and then to adulthood, when sexual maturity is attained. Similarly, in holometabolous insects, immature juveniles transit to the adult form through an intermediate pupal stage when larval tissues are eliminated and the imaginal progenitor cells form the adult structures. The identity of the larval, pupal, and adult stages depends on the sequential expression of the transcription factors chinmo, Br-C, and E93. However, how these transcription factors determine temporal identity in developing tissues is poorly understood. Here, we report on the role of the larval specifier chinmo in larval and adult progenitor cells during fly development. Interestingly, chinmo promotes growth in larval and imaginal tissues in a Br-C-independent and -dependent manner, respectively. In addition, we found that the absence of chinmo during metamorphosis is critical for proper adult differentiation. Importantly, we also provide evidence that, in contrast to the well-known role of chinmo as a pro-oncogene, Br-C and E93 act as tumour suppressors. Finally, we reveal that the function of chinmo as a juvenile specifier is conserved in hemimetabolous insects as its homolog has a similar role in Blatella germanica. Taken together, our results suggest that the sequential expression of the transcription factors Chinmo, Br-C and E93 during larva, pupa an adult respectively, coordinate the formation of the different organs that constitute the adult organism.
Egg, larva, pupa, adult: the life of many insects is structured around these four well-defined stages of development. After hatching, the larva grows until it reaches a certain size; when the right conditions are met, it then becomes a pupa and metamorphoses into an adult. Most larval cells die during metamorphosis; only a group known as imaginal cells survives, dividing and maturing to create pupal and adult tissues. Each of these developmental steps are linked to a particular genetic program deployed in response to a single stage-specifying gene. For instance, the activation of the Br-C gene triggers the transition from larva to pupa, while E93 initiates the transformation of the pupa into an adult. However, which stage-specifying gene controls larval identity remains unclear. Recent studies suggest that in fruit flies, a gene known as chinmo could be playing this role. In response, Chafino et al. explored how chinmo shapes the development of fruit fly larvae. The experiments showed that chinmo is activated in the juvenile stage, and that it is required for the larvae to grow properly and for larval and imaginal tissues to form. Conversely, it must be switched off for the insect to become a pupa and then an adult. Further work suggested that the role of chinmo as a larval specifier could have emerged early in insect evolution. Moreover, Chafino et al. revealed that chinmo could repress Br-C, an important characteristic since stage-specifying genes usually switch on sequentially by regulating each other. A closer look suggested that, in imaginal cells, chinmo promotes development by inhibiting Br-C; in larval cells, however, chinmo not only has a Brc-repressing role but it is also necessary for larval cells to grow. Additional experiments exploring the role of the stage-specifying genes in tumor formation showed that chinmo promotes cells proliferation while Br-C and E93 had tumor-suppressing properties. Overall, the work by Chafino et al. sheds new light on the genetic control of insect development, while also potentially providing a new perspective on how genes related to chinmo and Br-C contribute to the emergence of human cancers.
Asunto(s)
Proteínas de Insectos , Factores de Transcripción , Animales , Humanos , Niño , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Pupa , Proteínas de Insectos/genética , Proteínas de Insectos/metabolismo , Larva , Metamorfosis Biológica , Insectos , Regulación del Desarrollo de la Expresión GénicaRESUMEN
Animal development relies on a sequence of specific stages that allow the formation of adult structures with a determined size. In general, juvenile stages are dedicated mainly to growth, whereas last stages are devoted predominantly to the maturation of adult structures. In holometabolous insects, metamorphosis marks the end of the growth period as the animals stops feeding and initiate the final differentiation of the tissues. This transition is controlled by the steroid hormone ecdysone produced in the prothoracic gland. In Drosophila melanogaster different signals have been shown to regulate the production of ecdysone, such as PTTH/Torso, TGFß and Egfr signaling. However, to which extent the roles of these signals are conserved remains unknown. Here, we study the role of Egfr signaling in post-embryonic development of the basal holometabolous beetle Tribolium castaneum. We show that Tc-Egfr and Tc-pointed are required to induced a proper larval-pupal transition through the control of the expression of ecdysone biosynthetic genes. Furthermore, we identified an additional Tc-Egfr ligand in the Tribolium genome, the neuregulin-like protein Tc-Vein (Tc-Vn), which contributes to induce larval-pupal transition together with Tc-Spitz (Tc-Spi). Interestingly, we found that in addition to the redundant role in the control of pupa formation, each ligand possesses different functions in organ morphogenesis. Whereas Tc-Spi acts as the main ligand in urogomphi and gin traps, Tc-Vn is required in wings and elytra. Altogether, our findings show that in Tribolium, post-embryonic Tc-Egfr signaling activation depends on the presence of two ligands and that its role in metamorphic transition is conserved in holometabolous insects.
Asunto(s)
Receptores ErbB/fisiología , Proteínas de Insectos/fisiología , Metamorfosis Biológica/fisiología , Tribolium/crecimiento & desarrollo , Animales , Ecdisona/fisiología , Receptores ErbB/genética , Regulación del Desarrollo de la Expresión Génica , Proteínas de Insectos/genética , Larva/crecimiento & desarrollo , Metamorfosis Biológica/genética , Filogenia , Pupa/crecimiento & desarrollo , Reacción en Cadena en Tiempo Real de la Polimerasa , Transducción de Señal , Tribolium/genéticaRESUMEN
Proper formation of adult insects requires the integration of spatial and temporal regulatory axes. Whereas spatial information confers identity to each tissue, organ and appendage, temporal information specifies at which stage of development the animal is. Regardless of the type of post-embryonic development, either hemimetabolous or holometabolous, temporal specificity is achieved through interactions between the temporal identity genes Kr-h1, E93 and Br-C, whose sequential expression is controlled by the two major developmental hormones, 20-hydroxyecdysone and Juvenile hormone. Given the intimate regulatory connection between these three factors to specify life stage identity, we dubbed the regulatory axis that comprises these genes as the Metamorphic Gene Network (MGN). In this review, we survey the molecular mechanisms underlying the control by the MGN of stage identity and progression in hemimetabolous and holometabolous insects.
Asunto(s)
Regulación del Desarrollo de la Expresión Génica , Insectos/crecimiento & desarrollo , Insectos/genética , Animales , Ecdisterona , Redes Reguladoras de Genes , Hormonas Juveniles/metabolismo , Metamorfosis BiológicaRESUMEN
Understanding the mechanisms that determine final body size of animals is a central question in biology. In animals with determinate growth, such as mammals or insects, the size at which the immature organism transforms into the adult defines the final body size, as adult individuals do not grow [1]. In Drosophila, the growth period ends when the immature larva undergoes the metamorphic transition to develop the mature adult [2]. This metamorphic transition is triggered by a sharp increase of the steroid ecdysone, synthetized in the prothoracic gland (PG), that occurs at the end of the third instar larvae (L3) [3-6]. It is widely accepted that ecdysone biosynthesis in Drosophila is mainly induced by the activation of tyrosine kinase (RTK) Torso by the prothoracicotropic hormone (Ptth) produced into two pairs of neurosecretory cells that project their axons onto the PG [7, 8]. However, the fact that neither Ptth nor torso-null mutant animals arrest larval development but only present a delay in the larva-pupa transition [9-11] mandates for a reconsideration of the conventional model. Here, we show that Egfr signaling, rather than Ptth/torso, is the major contributor of ecdysone biosynthesis in Drosophila. We found that Egfr signaling is activated in the PG in an autocrine mode by the EGF ligands spitz and vein, which in turn are regulated by the levels of ecdysone. This regulatory positive feedback loop ensures the production of ecdysone to trigger metamorphosis by a progressive Egfr-dependent activation of MAPK/ERK pathway, thus determining the animal final body size.
Asunto(s)
Proteínas de Drosophila/genética , Drosophila melanogaster/genética , Ecdisona/biosíntesis , Receptores ErbB/genética , Receptores de Péptidos de Invertebrados/genética , Transducción de Señal/genética , Animales , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/crecimiento & desarrollo , Drosophila melanogaster/metabolismo , Receptores ErbB/metabolismo , Larva/crecimiento & desarrollo , Larva/metabolismo , Pupa/crecimiento & desarrollo , Pupa/metabolismo , Receptores de Péptidos de Invertebrados/metabolismoRESUMEN
Adult progenitor cells activation is a key event in the formation of adult organs. In Drosophila, formation of abdominal adult trachea depends on the specific activation of tracheal adult progenitors (tracheoblasts) at the Tr4 and Tr5 spiracular branches. Proliferation of these tracheoblasts generates a pool of tracheal cells that migrate toward the posterior part of the trachea by the activation of the branchless/fibroblast growth factor (Bnl/FGF) signaling to form the abdominal adult trachea. Here, we show that, in addition to migration, Bnl/FGF signaling, mediated by the transcription factor Pointed, is also required for tracheoblast proliferation. This tracheoblast activation relies on the expression of the FGF ligand bnl in their nearby branches. Finally, we show that, in the absence of the transcription factor Cut (Ct), Bnl/FGF signaling induces endoreplication of tracheoblasts partially by promoting fizzy-related expression. Altogether, our results suggest a dual role of Bnl/FGF signaling in tracheoblasts, inducing both proliferation and endoreplication, depending on the presence or absence of the transcription factor Ct, respectively.
Asunto(s)
Proliferación Celular/genética , Proteínas de Drosophila/metabolismo , Drosophila/genética , Drosophila/metabolismo , Endorreduplicación/genética , Factores de Crecimiento de Fibroblastos/metabolismo , Proteínas de Homeodominio/metabolismo , Proteínas Nucleares/metabolismo , Células Madre/metabolismo , Tráquea/citología , Factores de Transcripción/metabolismo , Animales , Animales Modificados Genéticamente , Movimiento Celular/genética , Drosophila/crecimiento & desarrollo , Femenino , Masculino , Morfogénesis/genética , Transducción de Señal/genética , Tráquea/crecimiento & desarrollo , Tráquea/metabolismo , TransgenesRESUMEN
The adult body size is species-specific and controlled by complex interactions between hormones and the IIS/TOR pathway. To analyze the role of target of rapamycin (TOR) in the growth and development of the insect, expression levels of TOR were silenced in the model and pest insect red flour beetle, Tribolium castaneum. Injection of dsRNA into the last larval instar decreased pupal mass and size, while the amount of food intake by the larvae was not affected. These results place TcTOR downstream of nutrition as a transducer for nutritional signals to increase larval growth. In addition, TcTOR-silencing notably decreased the size of the adult appendages. Analysis of the wings and elytra revealed a decrease in cell size and number of these appendages in the TcTOR-silenced insects. This reduction in size was correlated with a decrease of transcriptional levels of marker genes controlling the cell cycle. Altogether, these results suggest a pivotal role for TcTOR in integrating nutritional signals and regulation of body and appendages growth.
Asunto(s)
Pupa/crecimiento & desarrollo , Serina-Treonina Quinasas TOR/metabolismo , Tribolium/crecimiento & desarrollo , Animales , Tamaño Corporal , Ciclo Celular , Ingestión de Alimentos , Expresión Génica , Insulina/metabolismo , Pupa/citología , Tribolium/citología , Tribolium/enzimología , Alas de Animales/citologíaRESUMEN
Body size in holometabolous insects is determined by the size at which the juvenile larva undergoes metamorphosis to the pupal stage. To undergo larva-pupa transition, larva must reach a critical developmental checkpoint, the threshold size (TS); however, the molecular mechanisms through which the TS cues this transition remain to be fully characterized. Here, we use the flour beetle Tribolium castaneum to characterize the molecular mechanisms underlying entry into metamorphosis. We found that T. castaneum reaches a TS at the beginning of the last larval instar, which is associated with the downregulation of TcKr-h1 and the upregulation of TcE93 and TcBr-C. Unexpectedly, we found that while there is an association between TS and TcE93 upregulation, it is the latter that constitutes the molecular trigger for metamorphosis initiation. In light of our results, we evaluate the interactions that control the larva-pupa transition and suggest alternative models.
Asunto(s)
Proteínas de Insectos/fisiología , Metamorfosis Biológica/genética , Tribolium/genética , Animales , Tamaño Corporal , Proteínas de Insectos/genética , Proteínas de Insectos/metabolismo , Larva/anatomía & histología , Larva/genética , Larva/crecimiento & desarrollo , Tribolium/anatomía & histología , Tribolium/crecimiento & desarrollo , Regulación hacia ArribaRESUMEN
How several signaling pathways are coordinated to generate complex organs through regulation of tissue growth and patterning is a fundamental question in developmental biology. The larval trachea of Drosophila is composed of differentiated functional cells and groups of imaginal tracheoblasts that build the adult trachea during metamorphosis. Air sac primordium cells (ASP) are tracheal imaginal cells that form the dorsal air sacs that supply oxygen to the flight muscles of the Drosophila adult. The ASP emerges from the tracheal branch that connects to the wing disc by the activation of both Bnl-FGF/Btl and EGFR signaling pathways. Together, these pathways promote cell migration and proliferation. In this study we demonstrate that Vein (vn) is the EGF ligand responsible for the activation of the EGFR pathway in the ASP. We also find that the Bnl-FGF/Btl pathway regulates the expression of vn through the transcription factor PointedP2 (PntP2). Furthermore, we show that the FGF target gene escargot (esg) attenuates EGFR signaling at the tip cells of the developing ASP, reducing their mitotic rate to allow proper migration. Altogether, our results reveal a link between Bnl-FGF/Btl and EGFR signaling and provide novel insight into how the crosstalk of these pathways regulates migration and growth.
Asunto(s)
Sacos Aéreos/crecimiento & desarrollo , Proteínas de Unión al ADN/metabolismo , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/crecimiento & desarrollo , Factores de Crecimiento de Fibroblastos/metabolismo , Proteínas del Tejido Nervioso/metabolismo , Neurregulinas/metabolismo , Proteínas Proto-Oncogénicas/metabolismo , Factores de Transcripción/metabolismo , Sacos Aéreos/citología , Sacos Aéreos/metabolismo , Animales , Animales Modificados Genéticamente , Proteínas de Unión al ADN/genética , Proteínas de Drosophila/genética , Drosophila melanogaster/genética , Receptores ErbB/genética , Receptores ErbB/metabolismo , Femenino , Factores de Crecimiento de Fibroblastos/genética , Regulación del Desarrollo de la Expresión Génica , Larva , Masculino , Proteínas del Tejido Nervioso/genética , Neurregulinas/genética , Proteínas Tirosina Quinasas/genética , Proteínas Tirosina Quinasas/metabolismo , Proteínas Proto-Oncogénicas/genética , Receptores de Factores de Crecimiento de Fibroblastos/genética , Receptores de Factores de Crecimiento de Fibroblastos/metabolismo , Receptores de Péptidos de Invertebrados/genética , Receptores de Péptidos de Invertebrados/metabolismo , Transducción de Señal/genética , Factores de Transcripción/genéticaRESUMEN
A population of Drosophila adult tracheal progenitor cells arises from differentiated cells of the larval main trachea that retain the ability to reenter the cell cycle and give rise to the multiple adult tracheal cell types. These progenitors are unique to the second tracheal metamere as homologous cells from other segments, express fizzy-related (fzr), the Drosophila homolog of CDH1 protein of the APC complex, and enter endocycle and do not contribute to adult trachea. Here, we examine the mechanisms for their quiescence and show that they reenter the cell cycle by expression of string/cdc25 through ecdysone. Furthermore, we show that preventing endocycle entry is both necessary and sufficient for these tracheal cells to exhibit markers of adult progenitors, thus modifying their genetic program. Finally, we show that Hox-mediated regulation of fzr expression is responsible for progenitor identity and thus specifies a group of differentiated cells with facultative stem cell features.
Asunto(s)
Células Madre Adultas/citología , Ciclo Celular , Diferenciación Celular , Drosophila melanogaster/citología , Tráquea/citología , Células Madre Adultas/metabolismo , Animales , Proteínas de Drosophila/metabolismo , Femenino , MasculinoRESUMEN
Extracellular vesicles (EVs), including exosomes, have been widely recognized for their role in intercellular communication of the immune response system. In the past few years, significance has been given to exosomes in the induction and modulation of cell-fate-inducing signalling pathways, such as the Hedgehog (Hh), Wnts, Notch, transforming growth factor (TGF-ß), epidermal growth factor (EGF) and fibroblast growth factor (FGF) pathways, placing them in the wider context of development and also of cancer. These protein families induce signalling cascades responsible for tissue specification, homeostasis and maintenance. Exosomes contribute to cell-fate signal secretion, and vice versa exosome secretion can be induced by these proteins. Interestingly, exosomes can also transfer their mRNA to host cells or modulate the signalling pathways directly by the removal of downstream effector molecules from the cell. Surprisingly, much of what we know about the function of exosomes in cell determination is gathered from pathological transformed cancer cells and wound healing while data about their biogenesis and biology in normal developing and adult tissue lag behind. In this report, we will summarize some of the published literature and point to current advances and questions in this fast-developing topic. In a brief foray, we will also update and shortly discuss their potential in diagnosis and targeted cancer treatment.