RESUMEN
Epithelial-mesenchymal transition (EMT) encompasses dynamic changes in cellular organization from epithelial to mesenchymal phenotypes, which leads to functional changes in cell migration and invasion. EMT occurs in a diverse range of physiological and pathological conditions and is driven by a conserved set of inducing signals, transcriptional regulators and downstream effectors. With over 5,700 publications indexed by Web of Science in 2019 alone, research on EMT is expanding rapidly. This growing interest warrants the need for a consensus among researchers when referring to and undertaking research on EMT. This Consensus Statement, mediated by 'the EMT International Association' (TEMTIA), is the outcome of a 2-year-long discussion among EMT researchers and aims to both clarify the nomenclature and provide definitions and guidelines for EMT research in future publications. We trust that these guidelines will help to reduce misunderstanding and misinterpretation of research data generated in various experimental models and to promote cross-disciplinary collaboration to identify and address key open questions in this research field. While recognizing the importance of maintaining diversity in experimental approaches and conceptual frameworks, we emphasize that lasting contributions of EMT research to increasing our understanding of developmental processes and combatting cancer and other diseases depend on the adoption of a unified terminology to describe EMT.
Asunto(s)
Investigación Biomédica/normas , Transición Epitelial-Mesenquimal , Animales , Movimiento Celular , Plasticidad de la Célula , Consenso , Biología Evolutiva/normas , Humanos , Neoplasias/patología , Terminología como AsuntoRESUMEN
During the development of a holometabolous insect such as Drosophila, specific group of cells in the larva survive during metamorphosis, unlike the other larval cells, and finally give rise to the differentiated adult structures. These cells, also known as Adult Progenitor Cells (APCs), maintain their multipotent capacity, differentially respond to hormonal and nutritional signals, survive the intrinsic and environmental stress and respond to the final differentiation cues. However, not much is known about the specific molecular mechanisms that account for their unique characteristics. Here we show that a specific Drosophila APC gene, headcase (hdc), has a dual role in the normal development of these cells. It acts at a systemic level by controlling the hormone ecdysone in the prothoracic gland and at the same time it acts locally as a tissue growth suppressor in the APC clusters, where it modulates the activity of the TOR pathway and promotes their survival by contributing in the regulation of the Unfolded Protein Response. We also show that hdc provides protection against stress in the APCs and that its ectopic expression in cells that do not usually express hdc can confer these cells with an additional stress protection. Hdc is the founding member of a group of homolog proteins identified from C. elegans to humans, where has been found associated with cancer progression. The finding that the Drosophila hdc is specifically expressed in progenitor cells and that it provides protection against stress opens up a new hypothesis to be explored regarding the role of the human Heca and its contribution to carcinogenesis.
Asunto(s)
Células Madre Adultas/metabolismo , Proteínas de Drosophila/genética , Drosophila melanogaster/genética , Estrés Fisiológico/genética , Animales , Animales Modificados Genéticamente , Diferenciación Celular/genética , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/citología , Drosophila melanogaster/metabolismo , Ecdisona/metabolismo , Regulación del Desarrollo de la Expresión Génica , Humanos , Larva/citología , Larva/genética , Larva/crecimiento & desarrollo , Larva/metabolismo , Metamorfosis Biológica/genética , Microscopía Confocal , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal/genética , Serina-Treonina Quinasas TOR/genética , Serina-Treonina Quinasas TOR/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
During development, cells often switch between static and migratory behaviours. Such transitions are fundamental events in development and are linked to harmful consequences in pathology. It has long been considered that epithelial cells either migrate collectively as epithelial cells, or undergo an epithelial-to-mesenchymal transition and migrate as individual mesenchymal cells. Here, we assess what is currently known about in vivo cell migratory phenomena and hypothesise that such migratory behaviours do not fit into alternative and mutually exclusive categories. Rather, we propose that these categories can be viewed as the most extreme cases of a general continuum of morphological variety, with cells harbouring different degrees or combinations of epithelial and mesenchymal features and displaying an array of migratory behaviours.
Asunto(s)
Movimiento Celular/fisiología , Células Epiteliales/fisiología , Transición Epitelial-Mesenquimal/fisiología , Células Madre Mesenquimatosas/fisiología , Metástasis de la Neoplasia/patología , Neoplasias/patología , Uniones Adherentes/fisiología , Animales , Cadherinas/metabolismo , Adhesión Celular/fisiología , Desarrollo Embrionario/fisiología , Humanos , Mesodermo/citología , Mesodermo/fisiologíaRESUMEN
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
Clusters of differentiated cells contributing to organ structures retain the potential to re-enter the cell cycle and replace cells lost during development or upon damage. To do so, they must be designated spatially and respond to proper activation cues. Here we show that in the case of Drosophila differentiated larval tracheal cells, progenitor potential is conferred by the spatially restricted activity of the Snoo transcription cofactor. Furthermore, Dpp signalling regulated by endocrine hormonal cues provides the temporal trigger for their activation. Finally, we elucidate the genetic network elicited by Snoo and Dpp activity. These results illustrate a regulatory mechanism that translates intrinsic potential and extrinsic cues into the facultative stem cell features of differentiated progenitors.
Asunto(s)
Diferenciación Celular/genética , Proteínas de Drosophila/genética , Proteínas Nucleares/genética , Células Madre/citología , Factores de Transcripción/genética , Animales , Proteínas de Drosophila/biosíntesis , Drosophila melanogaster/genética , Drosophila melanogaster/crecimiento & desarrollo , Regulación del Desarrollo de la Expresión Génica , Redes Reguladoras de Genes , Larva/genética , Larva/crecimiento & desarrollo , Proteínas Nucleares/biosíntesis , Células Madre/metabolismo , Tráquea/citología , Tráquea/crecimiento & desarrollo , Factores de Transcripción/biosíntesisRESUMEN
The eggshell serves as a depository for proteins that play an important role in early embryonic development. In particular, the Drosophila eggshell is responsible for transferring asymmetries from the egg chamber to specify the regions at both ends of the embryo through the uneven activation of the Torso (Tor) receptor in its membrane. This process relies on the restricted expression of the gene torso-like (tsl) in subpopulations of follicle cells during oogenesis and its protein accumulation at both poles of the eggshell, but it is not known how this signal is transmitted to the embryo. Here, we show that Tsl accumulates at the embryonic plasma membrane, even in the absence of the Tor receptor. However, during oogenesis, we detected Tsl accumulation only at the eggshell. These results suggest that there is a two-step mechanism to transfer the asymmetric positional cues from the egg chamber into the early embryo: initial anchoring of Tsl at the eggshell as it is secreted, followed by its later translocation to the egg plasma membrane, where it enables Tor receptor activation. Translocation of anchored determinants from the eggshell might then regulate the spatial and temporal control of early embryonic developmental processes.
Asunto(s)
Blastodermo/metabolismo , Membrana Celular/metabolismo , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/embriología , Drosophila melanogaster/metabolismo , Cáscara de Huevo/metabolismo , Animales , Blastodermo/embriología , Embrión no Mamífero/metabolismo , Femenino , Modelos Biológicos , Folículo Ovárico/metabolismo , Transporte de ProteínasRESUMEN
OBJECTIVES: Unilateral spatial neglect (USN) is the incapacity to respond to stimuli presented opposite to a dysfunctional cerebral hemisphere. It is usually caused by non-dominant hemisphere lesions, leads to poorer prognosis and might be underdiagnosed. The objectives of the study were to ascertain the presence of USN in acute stroke patients and analyze the possible degree of underdiagnosis in a Stroke Unit. MATERIALS AND METHODS: Prospective study of consecutive non-dominant hemisphere stroke patients within a period of 21 months. "Line Bisection" and "Triangles Cancellation" tests were used for USN screening and "Circle Gap Detection Task" to confirm the USN. The results were compared with routine Stroke Unit assessment using the NIHSS to determine the possible degree of underdiagnosis. RESULTS: A total of 62 subjects, 38 women (61.29%), mean age of 74.05 (SD 10.5) years, were included. USN was diagnosed in 25 cases (40.3%) but 56% of them were not detected in routine evaluation using the NIHSS. CONCLUSIONS: Unilateral spatial neglect, a common cognitive deficit after acute stroke, is greatly underdiagnosed in routine Stroke Unit assessment. The use of simple USN-specific screening tools would improve diagnosis and therefore the possibility of implementing appropriate rehabilitation strategies.
Asunto(s)
Trastornos de la Percepción/diagnóstico , Accidente Cerebrovascular/complicaciones , Adulto , Anciano , Femenino , Lateralidad Funcional , Humanos , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Trastornos de la Percepción/etiología , Estudios ProspectivosRESUMEN
Classical novae are thermonuclear explosions in binary stellar systems containing a white dwarf accreting material from a close companion star. They repeatedly eject 10(-4)-10(-5) solar masses of nucleosynthetically enriched gas into the interstellar medium, recurring on intervals of decades to tens of millennia. They are probably the main sources of Galactic (15)N, (17)O and (13)C. The origin of the large enhancements and inhomogeneous distribution of these species observed in high-resolution spectra of ejected nova shells has, however, remained unexplained for almost half a century. Several mechanisms, including mixing by diffusion, shear or resonant gravity waves, have been proposed in the framework of one-dimensional or two-dimensional simulations, but none has hitherto proven successful because convective mixing can only be modelled accurately in three dimensions. Here we report the results of a three-dimensional nuclear-hydrodynamic simulation of mixing at the core-envelope interface during nova outbursts. We show that buoyant fingering drives vortices from the Kelvin-Helmholtz instability, which inevitably enriches the accreted envelope with material from the outer white-dwarf core. Such mixing also naturally produces large-scale chemical inhomogeneities. Both the metallicity enhancement and the intrinsic dispersions in the abundances are consistent with the observed values.
RESUMEN
BACKGROUND: The migration of individual cells relies on their capacity to evaluate differences across their bodies and to move either toward or against a chemoattractant or a chemorepellent signal respectively. However, the direction of collective migration is believed to depend on the internal organization of the cell cluster while the role of the external signal is limited to single out some cells in the cluster, conferring them with motility properties. RESULTS: Here we analyzed the role of Fibroblast Growth Factor (FGF) signaling in collective migration in the Drosophila trachea. While ligand-binding FGF receptor (FGFR) activity in a single cell can drive migration of a tracheal cluster, we show that activity from a constitutively activated FGFR cannot-an observation that contrasts with previously analyzed cases. CONCLUSIONS: Our results indicate that individual cells in the tracheal cluster can "read" differences in the distribution of FGFR activity and lead migration of the cluster accordingly. Thus, FGF can act as a chemoattractant rather than as a motogen in collective cell migration. This finding has many implications in both development and pathology.
Asunto(s)
Estructuras Animales/embriología , Movimiento Celular/fisiología , Proteínas de Drosophila/metabolismo , Embrión no Mamífero/embriología , Receptores de Factores de Crecimiento de Fibroblastos/metabolismo , Transducción de Señal/fisiología , Animales , Proteínas de Drosophila/genética , Drosophila melanogaster , Receptores de Factores de Crecimiento de Fibroblastos/genéticaRESUMEN
BACKGROUND: Mutations in Drosophila tumor suppressor genes (TSGs) lead to the formation of invasive tumors in the brain and imaginal discs. RESULTS: Here we studied the tumorigenic properties of imaginal discs mutant for the TSG gene lethal giant larvae (lgl). lgl mutant cells display the characteristic features of mammalian tumor cells: they can proliferate indefinitely, induce additional tracheogenesis (an insect counterpart of vasculogenesis) and invade neighboring tissues. Lgl mutant tissues exhibit high apoptotic levels, which lead to the activation of the Jun-N-Terminal Kinase (JNK) pathway. We propose that JNK is a key factor in the acquisition of these tumorigenic properties; it promotes cell proliferation and induces high levels of Mmp1 and confers tumor cells capacity to invade wild-type tissue. Noteworthy, lgl RNAi-mediated down-regulation does not produce similar transformations in the central nervous system (CNS), thereby indicating a fundamental difference between the cells of developing imaginal discs and those of differentiated organs. We discuss these results in the light of the "single big-hit origin" of some human pediatric or developmental cancers. CONCLUSIONS: Down-regulation of lgl in imaginal discs is sufficient to enhance tracheogenesis and to promote invasion and colonization of other larval structures including the CNS. Developmental Dynamics 245:834-843, 2016. © 2016 Wiley Periodicals, Inc.
Asunto(s)
Drosophila/citología , Drosophila/metabolismo , Larva/citología , Larva/metabolismo , Animales , Animales Modificados Genéticamente , Proliferación Celular/genética , Proliferación Celular/fisiología , Sistema Nervioso Central/citología , Sistema Nervioso Central/metabolismo , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Sistema de Señalización de MAP Quinasas/genética , Sistema de Señalización de MAP Quinasas/fisiología , Metaloproteinasa 1 de la Matriz/genética , Metaloproteinasa 1 de la Matriz/metabolismo , Proteínas Supresoras de Tumor/genética , Proteínas Supresoras de Tumor/metabolismoRESUMEN
The role of tip and rear cells in collective migration is still a matter of debate and their differences at the cytoskeletal level are poorly understood. Here, we analysed these issues in the Drosophila trachea, an organ that develops from the collective migration of clusters of cells that respond to Branchless (Bnl), a fibroblast growth factor (FGF) homologue expressed in surrounding tissues. We track individual cells in the migratory cluster and characterise their features and unveil two prototypical types of cytoskeletal organisation that account for tip and rear cells respectively. Indeed, once the former are specified, they remain as such throughout migration. Furthermore, we show that FGF signalling in a single tip cell can trigger the migration of the cells in the branch. Finally, we found specific Rac activation at the tip cells and analysed how FGF-independent cell features, such as adhesion and motility, act on coupling the behaviour of trailing and tip cells. Thus, the combined effect of FGF promoting leading cell behaviour and the modulation of cell properties in a cluster can account for the wide range of migratory events driven by FGF.
Asunto(s)
Movimiento Celular , Drosophila melanogaster/citología , Tráquea/citología , Animales , Agregación Celular , Forma de la Célula , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/enzimología , Drosophila melanogaster/genética , Activación Enzimática , Factores de Crecimiento de Fibroblastos/metabolismo , Ganglios de Invertebrados/citología , Ganglios de Invertebrados/metabolismo , Genes Dominantes , Mutación , Transducción de Señal , Proteína de Unión al GTP cdc42/metabolismo , Proteínas de Unión al GTP rac/metabolismo , Proteínas de Unión al GTP rho/metabolismoRESUMEN
Activating mutations in Wnt and EGFR/Ras signaling pathways are common in colorectal cancer (CRC). Remarkably, clonal co-activation of these pathways in the adult Drosophila midgut induces "tumor-like" overgrowths. Here, we show that, in these clones and in CRC cell lines, Dpp/TGF-ß acts as a tumor suppressor. Moreover, we discover that the Iroquois/IRX-family-protein Mirror downregulates the transcription of core components of the Dpp pathway, reducing its tumor suppressor activity. We also show that this genetic interaction is conserved in human CRC cells, where the Iro/IRX proteins IRX3 and IRX5 diminish the response to TGF-ß. IRX3 and IRX5 are upregulated in human adenomas, and their levels correlate inversely with the gene expression signature of response to TGF-ß. In addition, Irx5 expression confers a growth advantage in the presence of TGF-ß, but is selected against in its absence. Together, our results identify a set of Iro/IRX proteins as conserved negative regulators of Dpp/TGF-ß activity. We propose that during the characteristic adenoma-to-carcinoma transition of human CRC, the activity of IRX proteins could reduce the sensitivity to the cytostatic effect of TGF-ß, conferring a growth advantage to tumor cells prior to the acquisition of mutations in TGF-ß pathway components.
Asunto(s)
Adenocarcinoma/metabolismo , Carcinogénesis/metabolismo , Neoplasias Colorrectales/metabolismo , Proteínas de Homeodominio/metabolismo , Factores de Transcripción/metabolismo , Factor de Crecimiento Transformador beta/metabolismo , Animales , Carcinogénesis/genética , Línea Celular Tumoral , Células Cultivadas , Drosophila/genética , Drosophila/metabolismo , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Proteínas del Ojo/genética , Proteínas del Ojo/metabolismo , Proteínas de Homeodominio/genética , Humanos , Mucosa Intestinal/metabolismo , Factores de Transcripción/genética , Factor de Crecimiento Transformador beta/genética , Regulación hacia ArribaRESUMEN
BACKGROUND: Decisive information on the parameters involved in cognitive impairment in patients with chronic heart failure is as yet lacking. Our aim was to determine the functional and psychosocial variables related with cognitive impairment using the mini-mental-state examination (MMSE) with age-and education-corrected scores. METHODS: A cohort study of chronic heart failure patients included in an integrated multidisciplinary hospital/primary care program. The MMSE (corrected for age and education in the Spanish population) was administered at enrolment in the program. Analyses were performed in 525 patients. Demographic and clinical variables were collected. Comprehensive assessment included depression (Yesavage), family function (family APGAR), social network (Duke), dependence (Barthel Index), frailty (Barber), and comorbidities. Univariate and multivariate logistic regression were performed to determine the predictors of cognitive impairment. RESULTS: Cognitive impairment affected 145 patients (27.6 %). Explanatory factors were gender (OR: 2.77 (1.75-4.39) p < 0.001), ischemic etiology (OR: 1.99 (1.25-3.17) p = 0.004), frailty (OR: 1.58 (0.99 to 2.50, p =0.050), albumin > 3.5 (OR: 0.59 (0.35-0.99) p = 0.048), and beta-blocker treatment (OR: 0.36 (0.17 to 0.76, p = 0.007)). No association was found between cognitive impairment and social support or family function. CONCLUSION: The observed prevalence of cognitive impairment using MMSE corrected scores was 27.6 %. A global approach in the management of these patients is needed, especially focusing on women and patients with frailty, low albumin levels, and ischemic aetiology heart failure.
Asunto(s)
Disfunción Cognitiva/epidemiología , Anciano Frágil , Insuficiencia Cardíaca/etiología , Isquemia Miocárdica/complicaciones , Autoinforme , Anciano , Disfunción Cognitiva/diagnóstico , Disfunción Cognitiva/psicología , Comorbilidad , Femenino , Estudios de Seguimiento , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Isquemia Miocárdica/diagnóstico , Pruebas Neuropsicológicas , Educación del Paciente como Asunto , Prevalencia , Factores de Riesgo , Índice de Severidad de la Enfermedad , Distribución por Sexo , Factores Sexuales , España/epidemiologíaRESUMEN
The transcriptional repressor Capicua (Cic) controls multiple aspects of Drosophila embryogenesis and has been implicated in vertebrate development and human diseases. Receptor tyrosine kinases (RTKs) can antagonize Cic-dependent gene repression, but the mechanisms responsible for this effect are not fully understood. Based on genetic and imaging studies in the early Drosophila embryo, we found that Torso RTK signaling can increase the rate of Cic degradation by changing its subcellular localization. We propose that Cic is degraded predominantly in the cytoplasm and show that Torso reduces the stability of Cic by controlling the rates of its nucleocytoplasmic transport. This model accounts for the experimentally observed spatiotemporal dynamics of Cic in the early embryo and might explain RTK-dependent control of Cic in other developmental contexts.
Asunto(s)
Proteínas de Drosophila/metabolismo , Proteínas HMGB/metabolismo , Proteínas Tirosina Quinasas Receptoras/metabolismo , Proteínas Represoras/metabolismo , Animales , Western Blotting , Tipificación del Cuerpo/genética , Tipificación del Cuerpo/fisiología , Drosophila , Proteínas de Drosophila/genética , Femenino , Recuperación de Fluorescencia tras Fotoblanqueo , Regulación del Desarrollo de la Expresión Génica/genética , Regulación del Desarrollo de la Expresión Génica/fisiología , Proteínas HMGB/genética , Masculino , Proteínas Tirosina Quinasas Receptoras/genética , Proteínas Represoras/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Transducción de Señal/genética , Transducción de Señal/fisiologíaRESUMEN
Recent data have demonstrated a crucial role for the transcription factor SRF (serum response factor) downstream of VEGF and FGF signalling during branching morphogenesis. This is the case for sprouting angiogenesis in vertebrates, axonal branching in mammals and terminal branching of the Drosophila tracheal system. However, the specific functions of SRF in these processes remain unclear. Here, we establish the relative contributions of the Drosophila homologues of FGF [Branchless (BNL)] and SRF [Blistered (BS)] in terminal tracheal branching. Conversely to an extended view, we show that BNL triggers terminal branching initiation in a DSRF-independent mechanism and that DSRF transcription induced by BNL signalling is required to maintain terminal branch elongation. Moreover, we report that increased and continuous FGF signalling can trigger tracheal cells to develop full-length terminal branches in the absence of DSRF transcription. Our results indicate that DSRF acts as an amplifying step to sustain the progression of terminal branch elongation even in the wild-type conditions of FGF signalling.
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Proteínas de Drosophila/metabolismo , Factores de Crecimiento de Fibroblastos/metabolismo , Factor de Respuesta Sérica/metabolismo , Tráquea/embriología , Animales , Animales Modificados Genéticamente , Drosophila , Proteínas de Drosophila/genética , Regulación del Desarrollo de la Expresión Génica , Inmunohistoquímica , Organogénesis/fisiología , Factor de Respuesta Sérica/genética , Tráquea/metabolismoRESUMEN
This paper reviews Luria's model of the three functional units of the brain. To meet this objective, several issues were reviewed: the theory of functional systems and the contributions of phylogenesis and embryogenesis to the brain's functional organization. This review revealed several facts. In the first place, the relationship/integration of basic homeostatic needs with complex forms of behavior. Secondly, the multi-scale hierarchical and distributed organization of the brain and interactions between cells and systems. Thirdly, the phylogenetic role of exaptation, especially in basal ganglia and cerebellum expansion. Finally, the tripartite embryogenetic organization of the brain: rhinic, limbic/paralimbic, and supralimbic zones. Obviously, these principles of brain organization are in contradiction with attempts to establish separate functional brain units. The proposed new model is made up of two large integrated complexes: a primordial-limbic complex (Luria's Unit I) and a telencephalic-cortical complex (Luria's Units II and III). As a result, five functional units were delineated: Unit I. Primordial or preferential (brainstem), for life-support, behavioral modulation, and waking regulation; Unit II. Limbic and paralimbic systems, for emotions and hedonic evaluation (danger and relevance detection and contribution to reward/motivational processing) and the creation of cognitive maps (contextual memory, navigation, and generativity [imagination]); Unit III. Telencephalic-cortical, for sensorimotor and cognitive processing (gnosis, praxis, language, calculation, etc.), semantic and episodic (contextual) memory processing, and multimodal conscious agency; Unit IV. Basal ganglia systems, for behavior selection and reinforcement (reward-oriented behavior); Unit V. Cerebellar systems, for the prediction/anticipation (orthometric supervision) of the outcome of an action. The proposed brain units are nothing more than abstractions within the brain's simultaneous and distributed physiological processes. As function transcends anatomy, the model necessarily involves transition and overlap between structures. Beyond the classic approaches, this review includes information on recent systemic perspectives on functional brain organization. The limitations of this review are discussed.
Asunto(s)
Encéfalo , Procesos Mentales , Humanos , Filogenia , Encéfalo/fisiología , Memoria , LenguajeRESUMEN
OBJECTIVE: Stereo-electroencephalography (SEEG)-guided radiofrequency thermocoagulation (RFTC) is being used incrementally in the invasive diagnosis of epilepsy. There is currently a lack of information regarding the potential cognitive consequences of the extended use of this technique. This work describes, for the first time, the cognitive outcomes after RFTC in patients with temporal lobe epilepsy (TLE), evaluated longitudinally and using a control group. METHODS: Forty-eight adult patients with drug-resistant unilateral TLE (30 RFTC-treated patients and 18 controls) were evaluated using a comprehensive neuropsychological protocol at baseline. In the RFTC group, two follow-up assessments were performed at 3 months and 1 year. The control group was reevaluated after 1 year. Two analyses were performed: 1) group-level analyses, in which linear mixed models were applied according to TLE lateralization (intragroup and intergroup [RFTC vs control] comparisons), and 2) individual-level analyses, in which the Reliable Change Index (RCI) algorithm was developed and a 90% CI (cutoff ± 1.64) was used to describe neuropsychological outcomes at 1 year post-RFTC. A memory subanalysis was performed in hippocampal RFTC patients (25/30). A Spearman coefficient study was conducted to determine the correlation between cognitive change and thermocoagulated contacts. RESULTS: Left- and right-sided TLE patients treated with RFTC showed cognitive preservation at baseline. At a group level, the short-term evaluation, including verbal and visual memory, language, and executive functions, showed preservation in these domains and no significant differences compared with baseline. In the long-term follow-up assessment (1 year after RFTC), no significant intragroup changes were found, nor were significant changes found in comparison with the control group. The RCI algorithm showed that significant individual cognitive losses and gains were infrequent. Three patients presented with naming deficits, only 1 (3.3%) of whom showed a clinically significant deficit. Significant gains were more prevalent in executive function tests with a speed component (4/20 left-sided RFTC patients). Twenty-five of the 30 (83%) patients were treated with hippocampal RFTC. No patients experienced significant loss in verbal delayed memory in the left-sided RFTC sample or in visual delayed memory in the right-sided RFTC sample. The correlations between cognitive change and RFTC contacts were mostly nonsignificant. CONCLUSIONS: In the group-level comparisons, discernible cognitive impairment following RFTC was not evidenced. The majority of patients did not exhibit significant individual declines during the 1-year follow-up period. Notably, the procedural intervention yielded no substantial repercussions on memory functioning following hippocampal RFTC. These findings underscore the evidence supporting the cognitive preservation associated with SEEG-guided RFTC.