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2.
Sci Rep ; 13(1): 5277, 2023 04 20.
Article En | MEDLINE | ID: mdl-37081050

Sea level rise has accelerated during recent decades, exceeding rates recorded during the previous two millennia, and as a result many coastal habitats and species around the globe are being impacted. This situation is expected to worsen due to anthropogenically induced climate change. However, the magnitude and relevance of expected increase in sea level rise (SLR) is uncertain for marine and terrestrial species that are reliant on coastal habitat for foraging, resting or breeding. To address this, we showcase the use of a low-cost approach to assess the impacts of SLR on sea turtles under various Intergovernmental Panel on Climate Change (IPCC) SLR scenarios on different sea turtle nesting rookeries worldwide. The study considers seven sea turtle rookeries with five nesting species, categorized from vulnerable to critically endangered including leatherback turtles (Dermochelys coriacea), loggerhead turtles (Caretta caretta), hawksbill turtles (Eretmochelys imbricata), olive ridley turtles (Lepidochelys olivacea) and green turtles (Chelonia mydas). Our approach combines freely available digital elevation models for continental and remote island beaches across different ocean basins with projections of field data and SLR. Our case study focuses on five of the seven living sea turtle species. Under moderate climate change scenarios, by 2050 it is predicted that at some sea turtle nesting habitats 100% will be flooded, and under an extreme scenario many sea turtle rookeries could vanish. Overall, nesting beaches with low slope and those species nesting at open beaches such as leatherback and loggerheads sea turtles might be the most vulnerable by future SLR scenarios.


Sea Level Rise , Turtles , Animals , Plant Breeding , Climate Change , Ecosystem
3.
Development ; 150(9)2023 05 01.
Article En | MEDLINE | ID: mdl-37017267

Developmental senescence is a form of programmed senescence that contributes to morphogenesis during embryonic development. We showed recently that the SIX1 homeoprotein, an essential regulator of organogenesis, is also a repressor of adult cellular senescence. Alterations in the SIX/EYA pathway are linked to the human branchio-oto-renal (BOR) syndrome, a rare congenital disorder associated with defects in the ears, kidneys and branchial arches. Here, we have used Six1-deficient mice, an animal model of the BOR syndrome, to investigate whether dysfunction of senescence underpins the developmental defects associated with SIX1 deficiency. We have focused on the developing inner ear, an organ with physiological developmental senescence that is severely affected in Six1-deficient mice and BOR patients. We show aberrant levels and distribution of senescence markers in Six1-deficient inner ears concomitant with defective morphogenesis of senescent structures. Transcriptomic analysis and ex vivo assays support a link between aberrant senescence and altered morphogenesis in this model, associated with deregulation of the TGFß/BMP pathway. Our results show that misregulation of embryo senescence may lead to genetic developmental disorders, significantly expanding the connection between senescence and disease.


Branchio-Oto-Renal Syndrome , Ear, Inner , Adult , Humans , Mice , Animals , Protein Tyrosine Phosphatases/physiology , Intracellular Signaling Peptides and Proteins/metabolism , Nuclear Proteins/genetics , Branchio-Oto-Renal Syndrome/genetics , Homeodomain Proteins/metabolism
4.
J Mech Behav Biomed Mater ; 140: 105729, 2023 04.
Article En | MEDLINE | ID: mdl-36801780

The true stress-true strain curves of 11 Australian spider species from the Entelegynae lineage were tensile tested and classified based on the values of the alignment parameter, α*, in the framework of the Spider Silk Standardization Initiative (S3I). The application of the S3I methodology allowed the determination of the alignment parameter in all cases, and were found to range between α* = 0.03 and α* = 0.65. These data, in combination with previous results on other species included in the Initiative, were exploited to illustrate the potential of this approach by testing two simple hypotheses on the distribution of the alignment parameter throughout the lineage: (1) whether a uniform distribution may be compatible with the values obtained from the studied species, and (2) whether any trend may be established between the distribution of the α* parameter and phylogeny. In this regard, the lowest values of the α* parameter are found in some representatives of the Araneidae group, and larger values seem to be found as the evolutionary distance from this group increases. However, a significant number of outliers to this apparent general trend in terms of the values of the α* parameter are described.


Silk , Spiders , Animals , Tensile Strength , Australia
5.
Soft Matter ; 18(26): 4973-4982, 2022 Jul 06.
Article En | MEDLINE | ID: mdl-35748816

Silk gut fibers were produced from the silkworm Samia cynthia ricini silk glands by the usual procedure of immersion in a mildly acidic solution and subsequent stretching. The morphology of the silk guts was assessed by scanning electron microscopy, and their microstructure was assessed by infrared spectroscopy and X-ray diffraction. It was found that both naturally spun and Samia silk guts share a common semicrystalline microstructure. The mechanical characterization of the silk guts revealed that these fibers show an elastomeric behavior when tested in water, and exhibit a genuine ground state to which the fiber may revert independently of its previous loading history. In spite of its large cross-sectional area compared with naturally spun silk fibers, Samia silk guts show values of work to fracture up to 160 MJ m-3, much larger than those of most of their natural counterparts, and establish a new record value for this parameter in silk guts.


Bombyx , Silk , Animals , Silk/chemistry , Spectrophotometry, Infrared , X-Ray Diffraction
6.
Front Cell Dev Biol ; 9: 678760, 2021.
Article En | MEDLINE | ID: mdl-34179008

Sphingolipids are bioactive lipid components of cell membranes with important signal transduction functions in health and disease. Ceramide is the central building block for sphingolipid biosynthesis and is processed to form structurally and functionally distinct sphingolipids. Ceramide can be phosphorylated by ceramide kinase (CERK) to generate ceramide-1-phosphate, a cytoprotective signaling molecule that has been widely studied in multiple tissues and organs, including the developing otocyst. However, little is known about ceramide kinase regulation during inner ear development. Using chicken otocysts, we show that genes for CERK and other enzymes of ceramide metabolism are expressed during the early stages of inner ear development and that CERK is developmentally regulated at the otic vesicle stage. To explore its role in inner ear morphogenesis, we blocked CERK activity in organotypic cultures of otic vesicles with a specific inhibitor. Inhibition of CERK activity impaired proliferation and promoted apoptosis of epithelial otic progenitors. CERK inhibition also compromised neurogenesis of the acoustic-vestibular ganglion. Insulin-like growth factor-1 (IGF-1) is a key factor for proliferation, survival and differentiation in the chicken otocyst. CERK inhibition decreased IGF-1-induced AKT phosphorylation and blocked IGF-1-induced cell survival. Overall, our data suggest that CERK is activated as a central element in the network of anti-apoptotic pro-survival pathways elicited by IGF-1 during early inner ear development.

7.
Gerokomos (Madr., Ed. impr.) ; 32(2): 96-100, jun. 2021. tab, graf
Article Es | IBECS | ID: ibc-218615

Objetivo: Comparar la percepción de relaciones familiares y la resiliencia en adultos mayores. Metodología: Estudio cuantitativo, descriptivo, comparativo, prospectivo y de corte transversal; la muestra estuvo conformada por 130 adultos mayores de 60 años de diversas comunidades de la Región Lagunera, al norte de México, seleccionados por un muestreo no probabilístico a conveniencia. Para la recogida de datos se utilizaron el Test de percepción de relaciones familiares del anciano y la Escala de Resiliencia de Connor-Davidson. Los datos se analizaron en el programa SPSS v20 y se aplicaron frecuencias para variables cualitativas, medidas de tendencia central y dispersión para variables cuantitativas, y para la comparación de los grupos se utilizó la prueba de Kruskal Wallis. Resultados: La mayor parte de la muestra eran mujeres (76,9%) y el 56,2% no tenía pareja. Los tres grupos no mostraron diferencia significativa en las características sociodemográficas. El análisis inferencial mostró diferencia significativa entre la percepción de la relación familiar y el nivel de resiliencia en los adultos mayores, en los grupos de percepción disarmónica con los grupos de percepción poco armónica y armónica. Conclusiones: Existe diferencia entre la percepción de la relación familiar y el nivel de resiliencia en el adulto mayor; se observa que a mejor percepción de la relación familiar por el adulto más se incrementa el nivel de resiliencia (AU)


Objective: To compare the perception of family relations and resilience in older adults. Methodology: Quantitative, descriptive, comparative, prospective and cross-sectional study; the sample consisted of 130 adults over 60 years of age from diverse communities of the Lagunera Region, in northern Mexico, selected by a non-probabilistic sample at convenience. For the collection of data, the Elderly Family Relationship Perception Test and the Connor-Davidson Resilience Scale were used. The data were analyzed in the SPSS v20 program and frequencies were applied for qualitative variables, measures of central tendency and dispersion for quantitative variables, for comparison of the groups used the Kruskal Wallis test. Results: The majority of the sample were women (76.9%) and 56.2% did not have a partner. The three groups showed no significant difference in sociodemographic characteristics. The inferential analysis shows a significant difference between the perception of the family relationship and the level of resilience in the older adults, in the groups of disharmonic perception with the groups of perception that are not harmonious and harmonious. Conclusions: There is a difference between perception of the family relationship and the level of resilience in the older adult, it is observed the better perception of the family relationship by the older adult increases the level of resilience (AU)


Humans , Male , Female , Middle Aged , Aged , Aged, 80 and over , Resilience, Psychological , Family Relations/psychology , Perception , Health of the Elderly , Cross-Sectional Studies , Prospective Studies
8.
J Clin Lab Anal ; 35(3): e23672, 2021 Mar.
Article En | MEDLINE | ID: mdl-33258201

BACKGROUND: Our aims were to describe the first Mexican patient with abetalipoproteinemia and to perform a comparative analysis of biochemical, clinical, and genetic characteristics of 100 cases reported in the literature. METHODS: We performed biochemical and molecular screenings in a Mexican girl with extremely low lipid levels and in her family. Further, we integrated and evaluated the characteristics of the cases with abetalipoproteinemia described in the literature. RESULTS: Our patient is a six-year-old girl who presented vomiting, chronic diarrhea, failure to thrive, malabsorption, acanthocytosis, anemia, transaminases elevation, and extremely low lipid levels. MTTP gene sequencing revealed homozygosity for a novel mutation p.Gly417Valfs*12 (G deletion c.1250). With the analysis of the reported cases, 60 clinical features (14 classical and 46 non-classical) were observed, being the most common acanthocytosis (57.5%), malabsorption (43.7%), and diarrhea (42.5%); 48.8% of the patients presented only classic clinical features, while the remaining 51.2% developed secondary effects due to a fat-soluble vitamin deficiency. An odds ratio analysis disclosed that patients diagnosed after 10 years of age have an increased risk for presenting clinical complications (OR = 18.0; 95% CI 6.0-54.1, p < 0.0001). A great diversity of mutations in MTTP has been observed (n = 76, being the most common p.G865X and p.N139_E140) and some of them with possible residual activity. CONCLUSION: The first Mexican patient with abetalipoproteinemia presents a novel MTTP mutation p.Gly417Valfs*12. Three factors that could modulate the phenotype in abetalipoproteinemia were identified: age at diagnosis, treatment, and the causal mutation.


Abetalipoproteinemia/genetics , Carrier Proteins/genetics , Mutation , Abetalipoproteinemia/etiology , Adolescent , Adult , Child , Female , Humans , Male , Mexico , Middle Aged , Pedigree
9.
Heredity (Edinb) ; 122(4): 417-427, 2019 04.
Article En | MEDLINE | ID: mdl-30120366

Determining the processes responsible for phenotypic variation is one of the central tasks of evolutionary biology. While the importance of acoustic traits for foraging and communication in echolocating mammals suggests adaptation, the seldom-tested null hypothesis to explain trait divergence is genetic drift. Here we derive FST values from multi-locus coalescent isolation-with-migration models, and couple them with estimates of quantitative trait divergence, or PST, to test drift as the evolutionary process responsible for phenotypic divergence in island populations of the Pteronotus parnellii species complex. Compared to traditional comparisons of PST to FST, the migration-based estimates of FST are unidirectional instead of bidirectional, simultaneously integrate variation among loci and individuals, and posterior densities of PST and FST can be compared directly. We found the evolution of higher call frequencies is inconsistent with genetic drift for the Hispaniolan population, despite many generations of isolation from its Puerto Rican counterpart. While the Hispaniolan population displays dimorphism in call frequencies, the higher frequency of the females is incompatible with sexual selection. Instead, cultural drift toward higher frequencies among Hispaniolan females might explain the divergence. By integrating Bayesian coalescent and trait analyses, this study demonstrates a powerful approach to testing genetic drift as the default evolutionary mechanism of trait differentiation between populations.


Chiroptera/genetics , Echolocation , Genetic Drift , Models, Genetic , Acoustics , Animals , Bayes Theorem , Chiroptera/physiology , DNA, Mitochondrial/genetics , Female , Genetic Variation , Genotype , Islands , Phenotype , Quantitative Trait, Heritable
10.
PLoS One ; 13(4): e0194281, 2018.
Article En | MEDLINE | ID: mdl-29634720

In this study, we identify the means by which segmentally homologous neurons acquire different neuropeptide fates in Drosophila. Ventral abdominal (Va)-neurons in the A1 segment of the ventral nerve cord express DH31 and AstA neuropeptides (neuropeptidergic fate I) by virtue of Ubx activity, whereas the A2-A4 Va-neurons express the Capa neuropeptide (neuropeptidergic fate II) under the influence of abdA. These different fates are attained through segment-specific programs of neural subtype specification undergone by segmentally homologous neurons. This is an attractive alternative by which Hox genes can shape Drosophila segmental neural architecture (more sophisticated than the previously identified binary "to live" or "not to live" mechanism). These data refine our knowledge of the mechanisms involved in diversifying neuronal identity within the central nervous system.


Drosophila Proteins/metabolism , Drosophila melanogaster/embryology , Gene Expression Regulation, Developmental , Insect Hormones/metabolism , Nervous System/embryology , Neuropeptides/metabolism , Oligopeptides/metabolism , Animals , Body Patterning/genetics , Cell Lineage , Central Nervous System/metabolism , Drosophila melanogaster/metabolism , Female , Homeodomain Proteins/genetics , Male , Nervous System/metabolism , Neurons/metabolism , Nuclear Proteins/metabolism , Temperature , Transcription Factors/metabolism
11.
PLoS One ; 13(1): e0190361, 2018.
Article En | MEDLINE | ID: mdl-29342156

The secondary cysts of the fish pathogen oomycete Saprolegnia parasitica possess bundles of long hooked hairs that are characteristic to this economically important pathogenic species. Few studies have been carried out on elucidating their specific role in the S. parasitica life cycle and the role they may have in the infection process. We show here their function by employing several strategies that focus on descriptive, developmental and predictive approaches. The strength of attachment of the secondary cysts of this pathogen was compared to other closely related species where bundles of long hooked hairs are absent. We found that the attachment of the S. parasitica cysts was around three times stronger than that of other species. The time sequence and influence of selected factors on morphology and the number of the bundles of long hooked hairs conducted by scanning electron microscopy study revealed that these are dynamic structures. They are deployed early after encystment, i.e., within 30 sec of zoospore encystment, and the length, but not the number, of the bundles steadily increased over the encystment period. We also observed that the number and length of the bundles was influenced by the type of substrate and encystment treatment applied, suggesting that these structures can adapt to different substrates (glass or fish scales) and can be modulated by different signals (i.e., protein media, 50 mM CaCl2 concentrations, carbon particles). Immunolocalization studies evidenced the presence of an adhesive extracellular matrix. The bioinformatic analyses of the S. parasitica secreted proteins showed that there is a high expression of genes encoding domains of putative proteins related to the attachment process and cell adhesion (fibronectin and thrombospondin) coinciding with the deployment stage of the bundles of long hooked hairs formation. This suggests that the bundles are structures that might contribute to the adhesion of the cysts to the host because they are composed of these adhesive proteins and/or by increasing the surface of attachment of this extracellular matrix.


Fishes/parasitology , Saprolegnia/pathogenicity , Animals , Host-Parasite Interactions , Microscopy, Electron, Scanning , Microscopy, Electron, Transmission
12.
J Vis Exp ; (120)2017 02 03.
Article En | MEDLINE | ID: mdl-28190042

Common problems in the processing of biological samples for observations with the scanning electron microscope (SEM) include cell collapse, treatment of samples from wet microenvironments and cell destruction. Using young floral tissues, oomycete cysts, and fungi spores (Agaricales) as examples, specific protocols to process delicate samples are described here that overcome some of the main challenges in sample treatment for image capture under the SEM. Floral meristems fixed with FAA (Formalin-Acetic-Alcohol) and processed with the Critical Point Dryer (CPD) did not display collapsed cellular walls or distorted organs. These results are crucial for the reconstruction of floral development. A similar CPD-based treatment of samples from wet microenvironments, such as the glutaraldehyde-fixed oomycete cysts, is optimal to test the differential growth of diagnostic characteristics (e.g., the cyst spines) on different types of substrates. Destruction of nurse cells attached to fungi spores was avoided after rehydration, dehydration, and the CPD treatment, an important step for further functional studies of these cells. The protocols detailed here represent low-cost and rapid alternatives for the acquisition of good-quality images to reconstruct growth processes and to study diagnostic characteristics.


Fungi/ultrastructure , Microscopy, Electron, Scanning/methods , Oomycetes/ultrastructure , Plants/ultrastructure , Cell Wall/ultrastructure , Specimen Handling
13.
An Acad Bras Cienc ; 87(1): 249-74, 2015 Mar.
Article En | MEDLINE | ID: mdl-25806987

This paper is a floristic and phytosociological study of the dry forest communities of the Dominican Republic. A total of 69 relevés in dry forest biotopes were carried out. The samples were subsequently subjected to Detrended Correspondence Analysis for the determination and study of possible groupings. The study does not cover tree formations growing on serpentines, nor the so-called semideciduous forests, peculiar to areas with higher rainfall. A total of nine phytocoenoses were identified. The most significant results led to the description of six new phytosociological associations: Simaroubetum berteroani (thorny dry forest on coastal dunes), Phyllostylo rhamnoidis-Prosopidetum juliflorae (southern Dominican disturbed dry forest), Consoleo moniliformis-Camerarietum linearifoliae (dry forest on hard limestones), Lemaireocereo hystricis-Prosopidetum juliflorae (northern Dominican disturbed dry forest), Lycio americani-Prosopidetum juliflorae (disturbed dry forest on saline soils) and Guettardo ellipticae-Guapiretum discoloris (dry forest on flat-topped hillocks in Montecristi). This is an important step forward in the phytosociological and floristic studies of the Caribbean territories.

14.
Rev Invest Clin ; 66 Suppl 2: S9-S72, 2014 Aug.
Article Es | MEDLINE | ID: mdl-25706585

Cow's milk allergy (CMA) is an immune-based disease that has become an increasing problem. The diagnosis and management of CMA varies from one clinical setting to another and represents a challenge in pediatric practice. In addition, because nonallergic food reactions can be confused with CMA symptoms, there is an overdiagnosis of the disease. In response to these situations, pediatric specialties from recognized institutions throughout Latin America decided to develop a clinical guideline for diagnosis and management of cow's milk allergy. These guidelines include definitions, epidemiology, pathophysiology overview, clinical and evidencebased recommendations for the diagnosis and treatment of CMA. They also include prevention and prognosis sections and identify gaps in the current knowledge to be addressed through future research.


Milk Hypersensitivity/diagnosis , Milk Proteins/adverse effects , Practice Guidelines as Topic , Evidence-Based Medicine , Humans , Latin America , Milk Hypersensitivity/epidemiology , Milk Hypersensitivity/therapy , Milk Proteins/immunology , Prognosis
15.
PLoS One ; 8(6): e66037, 2013.
Article En | MEDLINE | ID: mdl-23840394

Nesting by three species of marine turtles persists in the Dominican Republic, despite historic threats and long-term population decline. We conducted a genetic survey of marine turtles in the Dominican Republic in order to link them with other rookeries around the Caribbean. We sequenced a 740bp fragment of the control region of the mitochondrial DNA of 92 samples from three marine turtle species [hawksbill (n = 48), green (n = 2) and leatherback (n = 42)], and incorporated published data from other nesting populations and foraging grounds. The leatherback turtle (Dermochelys coriacea) in the Dominican Republic appeared to be isolated from Awala-Yalimapo, Cayenne, Trinidad and St. Croix but connected with other Caribbean populations. Two distinct nesting populations of hawksbill turtles (Eremochelys imbricata) were detected in the Dominican Republic and exhibited interesting patterns of connectivity with other nesting sites and juvenile and adult male foraging aggregations. The green sea turtle (Chelonia mydas) has almost been extirpated from the Dominican Republic and limited inference could be made from our samples. Finally, results were compared with Lagrangian drifting buoys and published Lagrangian virtual particles that travelled through the Dominican Republic and Caribbean waters. Conservation implications of sink-source effects or genetic isolation derived from these complex inter-connections are discussed for each species and population.


Conservation of Natural Resources/methods , DNA, Mitochondrial/analysis , Sequence Analysis, DNA/methods , Turtles/classification , Animals , Caribbean Region , Dominican Republic , Female , Male , Phylogeny , Phylogeography , Turtles/genetics
16.
Ann Hepatol ; 12 Suppl 1: S3-S24, 2013.
Article En | MEDLINE | ID: mdl-31207845

INTRODUCTION: Extrahepatic portal vein obstruction is an important cause of portal hypertension among children. The etiology is heterogeneous and there are few evidences related to the optimal treatment. AIM AND METHODS: To establish guidelines for the diagnosis and treatment of EHPVO in children, a group of gastroenterologists and pediatric surgery experts reviewed and analyzed data reported in the literature and issued evidence-based recommendations. RESULTS: Pediatric EHPVO is idiopathic in most of the cases. Digestive hemorrhage and/or hypersplenism are the main symptoms. Doppler ultrasound is a non-invasive technique with a high degree of accuracy for the diagnosis. Morbidity is related to variceal bleeding, recurrent thrombosis, portal biliopathy and hypersplenism. Endoscopic therapy is effective in controlling acute variceal hemorrhage and it seems that vasoactive drug therapy can be helpful. For primary prophylaxis of variceal bleeding, there are insufficient data for the use of beta blockers or endoscopic therapy. For secondary prophylaxis, sclerotherapy or variceal band ligation is effective; there is scare evidence to recommend beta-blockers. Surgery shunt is indicated in children with variceal bleeding who fail endoscopic therapy and for symptomatic hypersplenism; spleno-renal or meso-ilio-cava shunting is the alternative when Mesorex bypass is not feasible due to anatomic problems or in centers with no experience. CONCLUSIONS: Prospective control studies are required for a better knowledge of the natural history of EHPVO, etiology identification including prothrombotic states, efficacy of beta-blockers and comparison with endoscopic therapy on primary and secondary prophylaxis.

17.
PLoS One ; 7(5): e36477, 2012.
Article En | MEDLINE | ID: mdl-22574167

HCN channels are becoming pharmacological targets mainly in cardiac diseases. But apart from their well-known role in heart pacemaking, these channels are widely expressed in the nervous system where they contribute to the neuron firing pattern. Consequently, abolishing Ih current might have detrimental consequences in a big repertoire of behavioral traits. Several studies in mammals have identified the Ih current as an important determinant of the firing activity of dopaminergic neurons, and recent evidences link alterations in this current to various dopamine-related disorders. We used the model organism Drosophila melanogaster to investigate how lack of Ih current affects dopamine levels and the behavioral consequences in the sleep:activity pattern. Unlike mammals, in Drosophila there is only one gene encoding HCN channels. We generated a deficiency of the DmIh core gene region and measured, by HPLC, levels of dopamine. Our data demonstrate daily variations of dopamine in wild-type fly heads. Lack of Ih current dramatically alters dopamine pattern, but different mechanisms seem to operate during light and dark conditions. Behaviorally, DmIh mutant flies display alterations in the rest:activity pattern, and altered circadian rhythms. Our data strongly suggest that Ih current is necessary to prevent dopamine overproduction at dark, while light input allows cycling of dopamine in an Ih current dependent manner. Moreover, lack of Ih current results in behavioral defects that are consistent with altered dopamine levels.


Circadian Rhythm , Dopamine/metabolism , Drosophila Proteins/metabolism , Drosophila melanogaster/physiology , Ion Channels/metabolism , Sleep/physiology , Animals , Behavior, Animal/physiology , Behavior, Animal/radiation effects , Circadian Rhythm/radiation effects , Darkness , Drosophila Proteins/deficiency , Drosophila Proteins/genetics , Drosophila melanogaster/genetics , Drosophila melanogaster/metabolism , Drosophila melanogaster/radiation effects , Gene Deletion , Ion Channels/deficiency , Ion Channels/genetics , Sleep/radiation effects
18.
PLoS One ; 7(1): e30790, 2012.
Article En | MEDLINE | ID: mdl-22292041

BACKGROUND: Otic neurons and sensory cells derive from common progenitors whose transition into mature cells requires the coordination of cell survival, proliferation and differentiation programmes. Neurotrophic support and survival of post-mitotic otic neurons have been intensively studied, but the bases underlying the regulation of programmed cell death in immature proliferative otic neuroblasts remains poorly understood. The protein kinase AKT acts as a node, playing a critical role in controlling cell survival and cell cycle progression. AKT is activated by trophic factors, including insulin-like growth factor I (IGF-I), through the generation of the lipidic second messenger phosphatidylinositol 3-phosphate by phosphatidylinositol 3-kinase (PI3K). Here we have investigated the role of IGF-dependent activation of the PI3K-AKT pathway in maintenance of otic neuroblasts. METHODOLOGY/PRINCIPAL FINDINGS: By using a combination of organotypic cultures of chicken (Gallus gallus) otic vesicles and acoustic-vestibular ganglia, Western blotting, immunohistochemistry and in situ hybridization, we show that IGF-I-activation of AKT protects neural progenitors from programmed cell death. IGF-I maintains otic neuroblasts in an undifferentiated and proliferative state, which is characterised by the upregulation of the forkhead box M1 (FoxM1) transcription factor. By contrast, our results indicate that post-mitotic p27(Kip)-positive neurons become IGF-I independent as they extend their neuronal processes. Neurons gradually reduce their expression of the Igf1r, while they increase that of the neurotrophin receptor, TrkC. CONCLUSIONS/SIGNIFICANCE: Proliferative otic neuroblasts are dependent on the activation of the PI3K-AKT pathway by IGF-I for survival during the otic neuronal progenitor phase of early inner ear development.


Ear, Inner/embryology , Ear, Inner/innervation , Insulin-Like Growth Factor I/pharmacology , Neural Stem Cells/drug effects , Oncogene Protein v-akt/physiology , Animals , Caspase 3/metabolism , Caspase 3/physiology , Cell Proliferation/drug effects , Cell Survival/drug effects , Cells, Cultured , Chick Embryo , Gene Expression Regulation, Developmental/drug effects , Gene Expression Regulation, Developmental/genetics , Models, Biological , Neural Stem Cells/metabolism , Neural Stem Cells/physiology , Neurons/cytology , Neurons/drug effects , Neurons/metabolism , Neurons/physiology , Oncogene Protein v-akt/genetics , Oncogene Protein v-akt/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Signal Transduction/drug effects , Signal Transduction/genetics , Signal Transduction/physiology , Time Factors
19.
Mech Dev ; 128(3-4): 208-21, 2011.
Article En | MEDLINE | ID: mdl-21236339

The central nervous system contains a wide variety of neuronal subclasses generated by neural progenitors. The achievement of a unique neural fate is the consequence of a sequence of early and increasingly restricted regulatory events, which culminates in the expression of a specific genetic combinatorial code that confers individual characteristics to the differentiated cell. How the earlier regulatory events influence post-mitotic cell fate decisions is beginning to be understood in the Drosophila NB 5-6 lineage. However, it remains unknown to what extent these events operate in other lineages. To better understand this issue, we have used a very highly specific marker that identifies a small subset of abdominal cells expressing the Drosophila neuropeptide Capa: the ABCA neurons. Our data support the birth of the ABCA neurons from NB 5-3 in a cas temporal window in the abdominal segments A2-A4. Moreover, we show that the ABCA neuron has an ABCA-sibling cell which dies by apoptosis. Surprisingly, both cells are also generated in the abdominal segments A5-A7, although they undergo apoptosis before expressing Capa. In addition, we have performed a targeted genetic screen to identify players involved in ABCA specification. We have found that the ABCA fate requires zfh2, grain, Grunge and hedgehog genes. Finally, we show that the NB 5-3 generates other subtype of Capa-expressing cells (SECAs) in the third suboesophageal segment, which are born during a pdm/cas temporal window, and have different genetic requirements for their specification.


Drosophila Proteins/metabolism , Drosophila melanogaster/genetics , Neurons/metabolism , Neuropeptides/metabolism , Abdomen/innervation , Animals , Antigens, Differentiation/metabolism , Body Patterning/genetics , Cell Death , DNA-Binding Proteins/metabolism , Drosophila Proteins/genetics , Drosophila melanogaster/cytology , Drosophila melanogaster/embryology , Gene Expression Regulation, Developmental , Gene Regulatory Networks , Hedgehog Proteins/metabolism , Nerve Tissue/cytology , Nerve Tissue/embryology , Nerve Tissue/metabolism , Neural Stem Cells/cytology , Neural Stem Cells/metabolism , Neurons/cytology , Neuropeptides/genetics , Receptors, Notch/metabolism , Signal Transduction , Transcription Factors/metabolism
20.
Mech Dev ; 127(9-12): 458-71, 2010.
Article En | MEDLINE | ID: mdl-20732418

It is becoming increasingly clear that the activation of specific terminal differentiation genes during neural development is critically dependent upon the establishment of unique combinatorial transcription factor codes within distinct neural cell subtypes. However, it is still unclear to which extent these codes are shared by lineage-unrelated neurons expressing the same terminal differentiation genes. Additionally, it is not known if the activation of a specific terminal differentiation gene is restricted to cells born at a particular developmental time point. Here, we utilize the terminal differentiation gene FMRFa which is expressed by the Ap4 and SE2 neurons in the Drosophila ventral nerve cord, to explore these issues in depth. We find that the Ap4 and SE2 neurons are generated by different neural progenitors and use different combinatorial codes to activate FMRFa expression. Additionally, we find that the Ap4 and SE2 neurons are generated in different temporal gene expression windows. Extending the investigation to include a second Drosophila terminal differentiation gene, Leucokinin, we find similar results, suggesting that neurons generated by different progenitors might commonly use different transcription factor codes to activate the same terminal differentiation gene. Furthermore, these results imply that the activation of a particular terminal differentiation gene in temporally unrestricted.


Cell Differentiation/genetics , Cell Lineage/genetics , Drosophila melanogaster/cytology , Drosophila melanogaster/genetics , Gene Expression Regulation, Developmental , Neurons/cytology , Neurons/metabolism , Animals , Biomarkers/metabolism , Body Patterning/genetics , Drosophila Proteins/genetics , Drosophila Proteins/metabolism , FMRFamide/genetics , FMRFamide/metabolism , Genes, Insect/genetics , Neuropeptides/genetics , Neuropeptides/metabolism , Phenotype , Time Factors
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