nuria romero - Profile on Academia.edu (original) (raw)

Papers by nuria romero

Research paper thumbnail of Neuroendocrine Control of <i>Drosophila</i> Larval Light Preference

Science, Sep 6, 2013

Animal development is coupled with innate behaviors that maximize chances of survival. Here we sh... more Animal development is coupled with innate behaviors that maximize chances of survival. Here we show that the prothoracicotropic hormone (PTTH), a neuropeptide that controls the developmental transition from juvenile stage to sexual maturation, also regulates light avoidance in Drosophila melanogaster larvae. PTTH, through its receptor Torso, acts on two light sensors, the Bolwig's organ and the peripheral class IV dendritic arborization neurons, to regulate light avoidance. We find that PTTH concomitantly promotes steroidogenesis and light avoidance at the end of larval stage, thereby driving animals towards a darker environment to initiate the immobile maturation phase. Thus, PTTH controls the decisions of when and where animals undergo metamorphosis, optimizing conditions for adult development.

Research paper thumbnail of Timing the Juvenile-Adult Neurohormonal Transition: Functions and Evolution

Frontiers in Endocrinology, 2021

Puberty and metamorphosis are two major developmental transitions linked to the reproductive matu... more Puberty and metamorphosis are two major developmental transitions linked to the reproductive maturation. In mammals and vertebrates, the central brain acts as a gatekeeper, timing the developmental transition through the activation of a neuroendocrine circuitry. In addition to reproduction, these neuroendocrine axes and the sustaining genetic network play additional roles in metabolism, sleep and behavior. Although neurohormonal axes regulating juvenile-adult transition have been classically considered the result of convergent evolution (i.e., analogous) between mammals and insects, recent findings challenge this idea, suggesting that at least some neuroendocrine circuits might be present in the common bilaterian ancestor Urbilateria. The initial signaling pathways that trigger the transition in different species appear to be of a single evolutionary origin and, consequently, many of the resulting functions are conserved with a few other molecular players being co-opted during evolu...

Research paper thumbnail of The immunophilin Zonda controls regulated exocytosis in endocrine and exocrine tissues

ABSTRACTExocytosis is a fundamental process in physiology, communication between cells, organs an... more ABSTRACTExocytosis is a fundamental process in physiology, communication between cells, organs and even organisms. Hormones, neuropeptides and antibodies, among other cargoes are packed in exocytic vesicles that need to reach and fuse with the plasma membrane to release their content to the extracellular milieu. Hundreds of proteins participate in this process and several others in its regulation. We report here a novel component of the exocytic machinery, the Drosophila transmembrane immunophilin Zonda (Zda), previously found to participate in autophagy. Zda is highly expressed in secretory tissues, and regulates exocytosis in at least three of them: the ring gland, insulin-producing cells and the salivary gland. Using the salivary gland as a model system, we found that Zda is required at final steps of the exocytic process for fusion of secretory granules to the plasma membrane. In a genetic screen we identified the small GTPase RalA as a crucial regulator of secretory granule exo...

Research paper thumbnail of Growth and Maturation in Development: A Fly’s Perspective

International Journal of Molecular Sciences, 2020

In mammals like humans, adult fitness is improved due to resource allocation, investing energy in... more In mammals like humans, adult fitness is improved due to resource allocation, investing energy in the developmental growth process during the juvenile period, and in reproduction at the adult stage. Therefore, the attainment of their target body height/size co-occurs with the acquisition of maturation, implying a need for coordination between mechanisms that regulate organismal growth and maturation timing. Insects like Drosophila melanogaster also define their adult body size by the end of the juvenile larval period. Recent studies in the fly have shown evolutionary conservation of the regulatory pathways controlling growth and maturation, suggesting the existence of common coordinator mechanisms between them. In this review, we will present an overview of the significant advancements in the coordination mechanisms ensuring developmental robustness in Drosophila. We will include (i) the characterization of feedback mechanisms between maturation and growth hormones, (ii) the recogni...

Research paper thumbnail of Prothoracicotropic hormone modulates environmental adaptive plasticity through the control of developmental timing

Development (Cambridge, England), Mar 21, 2018

Adult size and fitness are controlled by a combination of genetics and environmental cues. In, gr... more Adult size and fitness are controlled by a combination of genetics and environmental cues. In, growth is confined to the larval phase and final body size is impacted by the duration of this phase, which is under neuroendocrine control. The neuropeptide prothoracicotropic hormone (PTTH) has been proposed to play a central role in controlling the length of the larval phase through regulation of ecdysone production, a steroid hormone that initiates larval molting and metamorphosis. Here, we test this issue by examining the consequences of null mutations in thegene ondevelopment. Loss ofcauses several developmental defects including a delay in developmental timing, increase in critical weight, loss of coordination between body and imaginal disc growth, and reduced adult survival in sub-optimal environmental conditions like nutrition deprivation or high population density. We show that these defects are caused by a decrease in ecdysone production associated with altered transcription of ...

Research paper thumbnail of Des insulines pour orchestrer la croissance

Research paper thumbnail of Zonda is a novel early component of the autophagy pathway inDrosophila

Molecular Biology of the Cell, 2017

Autophagy is an evolutionary conserved process by which eukaryotic cells undergo self-digestion o... more Autophagy is an evolutionary conserved process by which eukaryotic cells undergo self-digestion of cytoplasmic components. Here we report that a novel Drosophila immunophilin, which we have named Zonda, is critically required for starvation-induced autophagy. We show that Zonda operates at early stages of the process, specifically for Vps34-mediated phosphatidylinositol 3-phosphate (PI3P) deposition. Zonda displays an even distribution under basal conditions and, soon after starvation, nucleates in endoplasmic reticulum–associated foci that colocalize with omegasome markers. Zonda nucleation depends on Atg1, Atg13, and Atg17 but does not require Vps34, Vps15, Atg6, or Atg14. Zonda interacts physically with Atg1 through its kinase domain, as well as with Atg6 and Vps34. We propose that Zonda is an early component of the autophagy cascade necessary for Vps34-dependent PI3P deposition and omegasome formation.

Research paper thumbnail of Drosophila Lgr3 Couples Organ Growth with Maturation and Ensures Developmental Stability

Current Biology, 2015

Highlights d The relaxin family receptor Lgr3 controls Dilp8-induced developmental delay d A sing... more Highlights d The relaxin family receptor Lgr3 controls Dilp8-induced developmental delay d A single pair of bilateral Lgr3-positive (GCL) neurons mediates Dilp8 function d GCL neurons physically interact with PTTH neurons d Lgr3 signaling in GCL neurons coordinates growth and limits developmental variability Authors

Research paper thumbnail of Central Role of the Oxygen-dependent Degradation Domain of Drosophila HIF /Sima in Oxygen-dependent Nuclear Export

Central Role of the Oxygen-dependent Degradation Domain of Drosophila HIF /Sima in Oxygen-dependent Nuclear Export

Molecular Biology of the Cell, 2009

The Drosophila HIFα homologue, Sima, is localized mainly in the cytoplasm in normoxia and accumul... more The Drosophila HIFα homologue, Sima, is localized mainly in the cytoplasm in normoxia and accumulates in the nucleus upon hypoxic exposure. We have characterized the mechanism governing Sima oxygen-dependent subcellular localization and found that Sima shuttles continuously between the nucleus and the cytoplasm. We have previously shown that nuclear import depends on an atypical bipartite nuclear localization signal mapping next to the C-terminus of the protein. We show here that nuclear export is mediated in part by a CRM1-dependent nuclear export signal localized in the oxygen-dependent degradation domain (ODDD). CRM1-dependent nuclear export requires both oxygen-dependent hydroxylation of a specific prolyl residue (Pro850) in the ODDD, and the activity of the von Hippel Lindau tumor suppressor factor. At high oxygen tension rapid nuclear export of Sima occurs, whereas in hypoxia, Sima nuclear export is largely inhibited. HIFα/Sima nucleo-cytoplasmic localization is the result of ...

Research paper thumbnail of Drosophila Genome-Wide RNAi Screen Identifies Multiple Regulators of HIF–Dependent Transcription in Hypoxia

PLoS Genetics, 2010

Hypoxia-inducible factors (HIFs) are a family of evolutionary conserved alpha-beta heterodimeric ... more Hypoxia-inducible factors (HIFs) are a family of evolutionary conserved alpha-beta heterodimeric transcription factors that induce a wide range of genes in response to low oxygen tension. Molecular mechanisms that mediate oxygen-dependent HIF regulation operate at the level of the alpha subunit, controlling protein stability, subcellular localization, and transcriptional coactivator recruitment. We have conducted an unbiased genome-wide RNA interference (RNAi) screen in Drosophila cells aimed to the identification of genes required for HIF activity. After 3 rounds of selection, 30 genes emerged as critical HIF regulators in hypoxia, most of which had not been previously associated with HIF biology. The list of genes includes components of chromatin remodeling complexes, transcription elongation factors, and translational regulators. One remarkable hit was the argonaute 1 (ago1) gene, a central element of the microRNA (miRNA) translational silencing machinery. Further studies confirmed the physiological role of the miRNA machinery in HIF-dependent transcription. This study reveals the occurrence of novel mechanisms of HIF regulation, which might contribute to developing novel strategies for therapeutic intervention of HIF-related pathologies, including heart attack, cancer, and stroke.

Research paper thumbnail of Cell Autonomy of HIF Effects in Drosophila: Tracheal Cells Sense Hypoxia and Induce Terminal Branch Sprouting

Developmental Cell, 2008

Drosophila tracheal terminal branches are plastic and have the capacity to sprout out projections... more Drosophila tracheal terminal branches are plastic and have the capacity to sprout out projections toward oxygen-starved areas, in a process analogous to mammalian angiogenesis. This response involves the upregulation of FGF/Branchless in hypoxic tissues, which binds its receptor Breathless on tracheal cells. Here, we show that extra sprouting depends on the Hypoxia-Inducible Factor (HIF)-a homolog Sima and on the HIF-prolyl hydroxylase Fatiga that operates as an oxygen sensor. In mild hypoxia, Sima accumulates in tracheal cells, where it induces breathless, and this induction is sufficient to provoke tracheal extra sprouting. In nontracheal cells, Sima contributes to branchless induction, whereas overexpression of Sima fails to attract terminal branch outgrowth, suggesting that HIF-independent components are also required for full induction of the ligand. We propose that the autonomous response to hypoxia that occurs in tracheal cells enhances tracheal sensitivity to increasing Branchless levels, and that this mechanism is a cardinal step in hypoxia-dependent tracheal sprouting.

Research paper thumbnail of PVF1/PVR signaling and apoptosis promotes the rotation and dorsal closure of the Drosophila male terminalia

The International Journal of Developmental Biology, 2004

The Drosophila adult male terminalia originate from the genital disc. During the pupal stages, th... more The Drosophila adult male terminalia originate from the genital disc. During the pupal stages, the external parts of terminalia evert from two ventral stalks; the everted left and right dorsal halves fuse at the dorsal midline. At the same time the male terminalia perform a 360º clockwise rotation. Several mutations are known to affect the rotation of the male terminalia, while none is known to affect dorsal closure. We show here that the Pvf1 gene, encoding one of the three Drosophila homologues of the mammalian VEGF/PDGF growth factors, is required for both processes. Males either mutant for Pvf1 or bearing a dominant negative form of Pvr or stasis (stai), the unique PVF receptor, do not complete either rotation or dorsal closure. Pvf1 expression in the genital disc is restricted to the A8 cells. However, PVF1/PVR signaling influences A8, A9 and A10 cells, suggesting that the PVF1 protein diffuses from its source. Flies hemizygous for the apoptotic genes hid, reaper and grim, or mutant for puckered which encodes a phosphatase that downregulates the n-Jun-N terminal kinase pathway, lead to the same phenotypes as mutations in PVF1/ PVR. Our results indicate that PVF1/PVR signaling functions not only in apoptotic phenomena but are also required during rotation and dorsal closure of the Drosophila male genital disc.

Research paper thumbnail of AstA Signaling Functions as an Evolutionary Conserved Mechanism Timing Juvenile to Adult Transition

Current Biology, 2019

Highlights d AstA/AstAR1 signaling times the onset of maturation by promoting PTTH secretion d As... more Highlights d AstA/AstAR1 signaling times the onset of maturation by promoting PTTH secretion d AstA/AstAR1 promotes juvenile growth by controlling Dilps secretion in the IPCs d AstA N1 neurons coordinate growth and maturation during larval development d AstA/AstAR1 achieves maximal activity in PTTH neurons at maturation onset

Research paper thumbnail of Neuroendocrine Control of <i>Drosophila</i> Larval Light Preference

Science, Sep 6, 2013

Animal development is coupled with innate behaviors that maximize chances of survival. Here we sh... more Animal development is coupled with innate behaviors that maximize chances of survival. Here we show that the prothoracicotropic hormone (PTTH), a neuropeptide that controls the developmental transition from juvenile stage to sexual maturation, also regulates light avoidance in Drosophila melanogaster larvae. PTTH, through its receptor Torso, acts on two light sensors, the Bolwig's organ and the peripheral class IV dendritic arborization neurons, to regulate light avoidance. We find that PTTH concomitantly promotes steroidogenesis and light avoidance at the end of larval stage, thereby driving animals towards a darker environment to initiate the immobile maturation phase. Thus, PTTH controls the decisions of when and where animals undergo metamorphosis, optimizing conditions for adult development.

Research paper thumbnail of Timing the Juvenile-Adult Neurohormonal Transition: Functions and Evolution

Frontiers in Endocrinology, 2021

Puberty and metamorphosis are two major developmental transitions linked to the reproductive matu... more Puberty and metamorphosis are two major developmental transitions linked to the reproductive maturation. In mammals and vertebrates, the central brain acts as a gatekeeper, timing the developmental transition through the activation of a neuroendocrine circuitry. In addition to reproduction, these neuroendocrine axes and the sustaining genetic network play additional roles in metabolism, sleep and behavior. Although neurohormonal axes regulating juvenile-adult transition have been classically considered the result of convergent evolution (i.e., analogous) between mammals and insects, recent findings challenge this idea, suggesting that at least some neuroendocrine circuits might be present in the common bilaterian ancestor Urbilateria. The initial signaling pathways that trigger the transition in different species appear to be of a single evolutionary origin and, consequently, many of the resulting functions are conserved with a few other molecular players being co-opted during evolu...

Research paper thumbnail of The immunophilin Zonda controls regulated exocytosis in endocrine and exocrine tissues

ABSTRACTExocytosis is a fundamental process in physiology, communication between cells, organs an... more ABSTRACTExocytosis is a fundamental process in physiology, communication between cells, organs and even organisms. Hormones, neuropeptides and antibodies, among other cargoes are packed in exocytic vesicles that need to reach and fuse with the plasma membrane to release their content to the extracellular milieu. Hundreds of proteins participate in this process and several others in its regulation. We report here a novel component of the exocytic machinery, the Drosophila transmembrane immunophilin Zonda (Zda), previously found to participate in autophagy. Zda is highly expressed in secretory tissues, and regulates exocytosis in at least three of them: the ring gland, insulin-producing cells and the salivary gland. Using the salivary gland as a model system, we found that Zda is required at final steps of the exocytic process for fusion of secretory granules to the plasma membrane. In a genetic screen we identified the small GTPase RalA as a crucial regulator of secretory granule exo...

Research paper thumbnail of Growth and Maturation in Development: A Fly’s Perspective

International Journal of Molecular Sciences, 2020

In mammals like humans, adult fitness is improved due to resource allocation, investing energy in... more In mammals like humans, adult fitness is improved due to resource allocation, investing energy in the developmental growth process during the juvenile period, and in reproduction at the adult stage. Therefore, the attainment of their target body height/size co-occurs with the acquisition of maturation, implying a need for coordination between mechanisms that regulate organismal growth and maturation timing. Insects like Drosophila melanogaster also define their adult body size by the end of the juvenile larval period. Recent studies in the fly have shown evolutionary conservation of the regulatory pathways controlling growth and maturation, suggesting the existence of common coordinator mechanisms between them. In this review, we will present an overview of the significant advancements in the coordination mechanisms ensuring developmental robustness in Drosophila. We will include (i) the characterization of feedback mechanisms between maturation and growth hormones, (ii) the recogni...

Research paper thumbnail of Prothoracicotropic hormone modulates environmental adaptive plasticity through the control of developmental timing

Development (Cambridge, England), Mar 21, 2018

Adult size and fitness are controlled by a combination of genetics and environmental cues. In, gr... more Adult size and fitness are controlled by a combination of genetics and environmental cues. In, growth is confined to the larval phase and final body size is impacted by the duration of this phase, which is under neuroendocrine control. The neuropeptide prothoracicotropic hormone (PTTH) has been proposed to play a central role in controlling the length of the larval phase through regulation of ecdysone production, a steroid hormone that initiates larval molting and metamorphosis. Here, we test this issue by examining the consequences of null mutations in thegene ondevelopment. Loss ofcauses several developmental defects including a delay in developmental timing, increase in critical weight, loss of coordination between body and imaginal disc growth, and reduced adult survival in sub-optimal environmental conditions like nutrition deprivation or high population density. We show that these defects are caused by a decrease in ecdysone production associated with altered transcription of ...

Research paper thumbnail of Des insulines pour orchestrer la croissance

Research paper thumbnail of Zonda is a novel early component of the autophagy pathway inDrosophila

Molecular Biology of the Cell, 2017

Autophagy is an evolutionary conserved process by which eukaryotic cells undergo self-digestion o... more Autophagy is an evolutionary conserved process by which eukaryotic cells undergo self-digestion of cytoplasmic components. Here we report that a novel Drosophila immunophilin, which we have named Zonda, is critically required for starvation-induced autophagy. We show that Zonda operates at early stages of the process, specifically for Vps34-mediated phosphatidylinositol 3-phosphate (PI3P) deposition. Zonda displays an even distribution under basal conditions and, soon after starvation, nucleates in endoplasmic reticulum–associated foci that colocalize with omegasome markers. Zonda nucleation depends on Atg1, Atg13, and Atg17 but does not require Vps34, Vps15, Atg6, or Atg14. Zonda interacts physically with Atg1 through its kinase domain, as well as with Atg6 and Vps34. We propose that Zonda is an early component of the autophagy cascade necessary for Vps34-dependent PI3P deposition and omegasome formation.

Research paper thumbnail of Drosophila Lgr3 Couples Organ Growth with Maturation and Ensures Developmental Stability

Current Biology, 2015

Highlights d The relaxin family receptor Lgr3 controls Dilp8-induced developmental delay d A sing... more Highlights d The relaxin family receptor Lgr3 controls Dilp8-induced developmental delay d A single pair of bilateral Lgr3-positive (GCL) neurons mediates Dilp8 function d GCL neurons physically interact with PTTH neurons d Lgr3 signaling in GCL neurons coordinates growth and limits developmental variability Authors

Research paper thumbnail of Central Role of the Oxygen-dependent Degradation Domain of Drosophila HIF /Sima in Oxygen-dependent Nuclear Export

Central Role of the Oxygen-dependent Degradation Domain of Drosophila HIF /Sima in Oxygen-dependent Nuclear Export

Molecular Biology of the Cell, 2009

The Drosophila HIFα homologue, Sima, is localized mainly in the cytoplasm in normoxia and accumul... more The Drosophila HIFα homologue, Sima, is localized mainly in the cytoplasm in normoxia and accumulates in the nucleus upon hypoxic exposure. We have characterized the mechanism governing Sima oxygen-dependent subcellular localization and found that Sima shuttles continuously between the nucleus and the cytoplasm. We have previously shown that nuclear import depends on an atypical bipartite nuclear localization signal mapping next to the C-terminus of the protein. We show here that nuclear export is mediated in part by a CRM1-dependent nuclear export signal localized in the oxygen-dependent degradation domain (ODDD). CRM1-dependent nuclear export requires both oxygen-dependent hydroxylation of a specific prolyl residue (Pro850) in the ODDD, and the activity of the von Hippel Lindau tumor suppressor factor. At high oxygen tension rapid nuclear export of Sima occurs, whereas in hypoxia, Sima nuclear export is largely inhibited. HIFα/Sima nucleo-cytoplasmic localization is the result of ...

Research paper thumbnail of Drosophila Genome-Wide RNAi Screen Identifies Multiple Regulators of HIF–Dependent Transcription in Hypoxia

PLoS Genetics, 2010

Hypoxia-inducible factors (HIFs) are a family of evolutionary conserved alpha-beta heterodimeric ... more Hypoxia-inducible factors (HIFs) are a family of evolutionary conserved alpha-beta heterodimeric transcription factors that induce a wide range of genes in response to low oxygen tension. Molecular mechanisms that mediate oxygen-dependent HIF regulation operate at the level of the alpha subunit, controlling protein stability, subcellular localization, and transcriptional coactivator recruitment. We have conducted an unbiased genome-wide RNA interference (RNAi) screen in Drosophila cells aimed to the identification of genes required for HIF activity. After 3 rounds of selection, 30 genes emerged as critical HIF regulators in hypoxia, most of which had not been previously associated with HIF biology. The list of genes includes components of chromatin remodeling complexes, transcription elongation factors, and translational regulators. One remarkable hit was the argonaute 1 (ago1) gene, a central element of the microRNA (miRNA) translational silencing machinery. Further studies confirmed the physiological role of the miRNA machinery in HIF-dependent transcription. This study reveals the occurrence of novel mechanisms of HIF regulation, which might contribute to developing novel strategies for therapeutic intervention of HIF-related pathologies, including heart attack, cancer, and stroke.

Research paper thumbnail of Cell Autonomy of HIF Effects in Drosophila: Tracheal Cells Sense Hypoxia and Induce Terminal Branch Sprouting

Developmental Cell, 2008

Drosophila tracheal terminal branches are plastic and have the capacity to sprout out projections... more Drosophila tracheal terminal branches are plastic and have the capacity to sprout out projections toward oxygen-starved areas, in a process analogous to mammalian angiogenesis. This response involves the upregulation of FGF/Branchless in hypoxic tissues, which binds its receptor Breathless on tracheal cells. Here, we show that extra sprouting depends on the Hypoxia-Inducible Factor (HIF)-a homolog Sima and on the HIF-prolyl hydroxylase Fatiga that operates as an oxygen sensor. In mild hypoxia, Sima accumulates in tracheal cells, where it induces breathless, and this induction is sufficient to provoke tracheal extra sprouting. In nontracheal cells, Sima contributes to branchless induction, whereas overexpression of Sima fails to attract terminal branch outgrowth, suggesting that HIF-independent components are also required for full induction of the ligand. We propose that the autonomous response to hypoxia that occurs in tracheal cells enhances tracheal sensitivity to increasing Branchless levels, and that this mechanism is a cardinal step in hypoxia-dependent tracheal sprouting.

Research paper thumbnail of PVF1/PVR signaling and apoptosis promotes the rotation and dorsal closure of the Drosophila male terminalia

The International Journal of Developmental Biology, 2004

The Drosophila adult male terminalia originate from the genital disc. During the pupal stages, th... more The Drosophila adult male terminalia originate from the genital disc. During the pupal stages, the external parts of terminalia evert from two ventral stalks; the everted left and right dorsal halves fuse at the dorsal midline. At the same time the male terminalia perform a 360º clockwise rotation. Several mutations are known to affect the rotation of the male terminalia, while none is known to affect dorsal closure. We show here that the Pvf1 gene, encoding one of the three Drosophila homologues of the mammalian VEGF/PDGF growth factors, is required for both processes. Males either mutant for Pvf1 or bearing a dominant negative form of Pvr or stasis (stai), the unique PVF receptor, do not complete either rotation or dorsal closure. Pvf1 expression in the genital disc is restricted to the A8 cells. However, PVF1/PVR signaling influences A8, A9 and A10 cells, suggesting that the PVF1 protein diffuses from its source. Flies hemizygous for the apoptotic genes hid, reaper and grim, or mutant for puckered which encodes a phosphatase that downregulates the n-Jun-N terminal kinase pathway, lead to the same phenotypes as mutations in PVF1/ PVR. Our results indicate that PVF1/PVR signaling functions not only in apoptotic phenomena but are also required during rotation and dorsal closure of the Drosophila male genital disc.

Research paper thumbnail of AstA Signaling Functions as an Evolutionary Conserved Mechanism Timing Juvenile to Adult Transition

Current Biology, 2019

Highlights d AstA/AstAR1 signaling times the onset of maturation by promoting PTTH secretion d As... more Highlights d AstA/AstAR1 signaling times the onset of maturation by promoting PTTH secretion d AstA/AstAR1 promotes juvenile growth by controlling Dilps secretion in the IPCs d AstA N1 neurons coordinate growth and maturation during larval development d AstA/AstAR1 achieves maximal activity in PTTH neurons at maturation onset