RESUMEN

High-quality DNA extraction from organoids is an important step in molecular genetics research. Here, we show that a lysis buffer from the field of Caenorhabditis elegans research, called Single Worm Lysis Buffer (SWLB), is a low-cost, yet reliable method for DNA extraction from mammalian organoids. SWLB is superior in terms of price, storage, hands-on time and sustainability compared to current standardized DNA extraction protocols, while equally effective. This work indicates that it is useful to compare methods from different model systems, such as mammalian organoids and invertebrate nematodes, to find useful alternatives for research methodologies.

RESUMEN

Many developmental processes depend on precise temporal control of gene expression. We have previously established a theoretical framework for regulatory strategies that can govern such high temporal precision, but experimental validation of these predictions was still lacking. Here, we use the time-dependent expression of a Wnt receptor that controls neuroblast migration in Caenorhabditis elegans as a tractable system to study a robust, cell-intrinsic timing mechanism in vivo. Single-molecule mRNA quantification showed that the expression of the receptor increases non-linearly, a dynamic that is predicted to enhance timing precision over an unregulated, linear increase in timekeeper abundance. We show that this upregulation depends on transcriptional activation, providing in vivo evidence for a model in which the timing of receptor expression is regulated through an accumulating activator that triggers expression when a specific threshold is reached. This timing mechanism acts across a cell division that occurs in the neuroblast lineage and is influenced by the asymmetry of the division. Finally, we show that positive feedback of receptor expression through the canonical Wnt pathway enhances temporal precision. We conclude that robust cell-intrinsic timing can be achieved by combining regulation and feedback of the timekeeper gene.

Asunto(s)

Proteínas de Caenorhabditis elegans , Factores de Transcripción , Animales , Factores de Transcripción/metabolismo , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Retroalimentación , Caenorhabditis elegans/metabolismo , Movimiento Celular/genética , Regulación del Desarrollo de la Expresión Génica

RESUMEN

Polyploid cells contain more than 2 copies of the genome and are found in many plant and animal tissues. Different types of polyploidy exist, in which the genome is confined to either 1 nucleus (mononucleation) or 2 or more nuclei (multinucleation). Despite the widespread occurrence of polyploidy, the functional significance of different types of polyploidy is largely unknown. Here, we assess the function of multinucleation in Caenorhabditis elegans intestinal cells through specific inhibition of binucleation without altering genome ploidy. Through single-worm RNA sequencing, we find that binucleation is important for tissue-specific gene expression, most prominently for genes that show a rapid up-regulation at the transition from larval development to adulthood. Regulated genes include vitellogenins, which encode yolk proteins that facilitate nutrient transport to the germline. We find that reduced expression of vitellogenins in mononucleated intestinal cells leads to progeny with developmental delays and reduced fitness. Together, our results show that binucleation facilitates rapid up-regulation of intestine-specific gene expression during development, independently of genome ploidy, underscoring the importance of spatial genome organization for polyploid cell function.

Asunto(s)

Poliploidía , Vitelogeninas , Animales , Caenorhabditis elegans/genética , División Celular , Núcleo Celular/genética , Expresión Génica , Vitelogeninas/genética

RESUMEN

RNA tomography or tomo-seq combines mRNA sequencing and cryo-sectioning to spatially resolve gene expression. We have adapted this method for the nematode Caenorhabditis elegans to generate anteroposterior gene expression maps at near-cellular resolution. Here, we provide a detailed overview of the method and present two approaches: one that includes RNA isolation for maximum sensitivity and one that is suitable for partial automatization and is therefore less time-consuming. For complete details on the use and execution of this protocol, please refer to Ebbing et al. (2018).

Asunto(s)

Caenorhabditis elegans , Perfilación de la Expresión Génica/métodos , Análisis de la Célula Individual/métodos , Tomografía/métodos , Animales , Caenorhabditis elegans/química , Caenorhabditis elegans/genética , Caenorhabditis elegans/metabolismo , ARN Mensajero/análisis , ARN Mensajero/genética , ARN Mensajero/metabolismo , Análisis de Secuencia de ARN/métodos , Transcriptoma/genética

RESUMEN

Members of the Wnt family of secreted glycoproteins regulate cell migration through distinct canonical and noncanonical signaling pathways. Studies of vertebrate development and disease have shown that these pathways can have opposing effects on cell migration, but the mechanism of this functional interplay is not known. In the nematode Caenorhabditis elegans, a switch from noncanonical to canonical Wnt signaling terminates the long-range migration of the QR neuroblast descendants, providing a tractable system to study this mechanism in vivo. Here, we show that noncanonical Wnt signaling acts through PIX-1/RhoGEF, while canonical signaling directly activates the Slt-Robo pathway component EVA-1/EVA1C and the Rho GTPase-activating protein RGA-9b/ARHGAP, which are required for migration inhibition. Our results support a model in which cross-talk between noncanonical and canonical Wnt signaling occurs through antagonistic regulation of the Rho GTPases that drive cell migration.

Asunto(s)

Proteínas de Caenorhabditis elegans/metabolismo , Movimiento Celular , Proteínas Activadoras de GTPasa/metabolismo , Proteínas del Tejido Nervioso/metabolismo , Células-Madre Neurales/metabolismo , Receptores Inmunológicos/metabolismo , Vía de Señalización Wnt , Animales , Caenorhabditis elegans , Proteínas de Caenorhabditis elegans/genética , Movimiento Celular/genética , Regulación de la Expresión Génica , Proteínas del Tejido Nervioso/genética , Células-Madre Neurales/citología , Receptores Inmunológicos/genética , Proteínas Roundabout

RESUMEN

Divergence of gene function and expression during development can give rise to phenotypic differences at the level of cells, tissues, organs, and ultimately whole organisms. To gain insights into the evolution of gene expression and novel genes at spatial resolution, we compared the spatially resolved transcriptomes of two distantly related nematodes, Caenorhabditis elegans and Pristionchus pacificus, that diverged 60-90 Ma. The spatial transcriptomes of adult worms show little evidence for strong conservation at the level of single genes. Instead, regional expression is largely driven by recent duplication and emergence of novel genes. Estimation of gene ages across anatomical structures revealed an enrichment of novel genes in sperm-related regions. This provides first evidence in nematodes for the "out of testis" hypothesis that has been previously postulated based on studies in Drosophila and mammals. "Out of testis" genes represent a mix of products of pervasive transcription as well as fast evolving members of ancient gene families. Strikingly, numerous novel genes have known functions during meiosis in Caenorhabditis elegans indicating that even universal processes such as meiosis may be targets of rapid evolution. Our study highlights the importance of novel genes in generating phenotypic diversity and explicitly characterizes gene origination in sperm-related regions. Furthermore, it proposes new functions for previously uncharacterized genes and establishes the spatial transcriptome of Pristionchus pacificus as a catalog for future studies on the evolution of gene expression and function.

Asunto(s)

Caenorhabditis elegans/genética , Evolución Molecular , Familia de Multigenes , Espermatozoides , Transcriptoma , Animales , Caenorhabditis elegans/metabolismo , Duplicación de Gen , Perfilación de la Expresión Génica , Genoma de los Helmintos , Masculino , Meiosis/genética , Filogenia , Espermatogénesis/genética , Testículo/fisiología

RESUMEN

Cellular behaviors such as migration, division, and differentiation rely on precise timing, and yet the molecular events that govern these behaviors are highly stochastic. We investigate regulatory strategies that decrease the timing noise of molecular events. Autoregulatory feedback increases noise. Yet we find that in the presence of regulation by a second species, autoregulatory feedback decreases noise. To explain this finding, we develop a method to calculate the optimal regulation function that minimizes the timing noise. The method reveals that the combination of feedback and regulation minimizes noise by maximizing the number of molecular events that must happen in sequence before a threshold is crossed. We compute the optimal timing precision for all two-node networks with regulation and feedback, derive a generic lower bound on timing noise, and discuss our results in the context of neuroblast migration during Caenorhabditis elegans development.

Asunto(s)

Retroalimentación Fisiológica , Homeostasis , Modelos Biológicos , Animales , Caenorhabditis elegans/metabolismo , Movimiento Celular , Cinética

RESUMEN

Single-cell isolation and transcriptomic analysis of a specific cell type or tissue offers the possibility of studying cell function and heterogeneity in time-dependent processes with remarkable resolution. The reduced tissue complexity and highly stereotyped development of Caenorhabditis elegans, combined with an extensive genetic toolbox and the ease of growing large tightly synchronized populations makes it an exceptional model organism for the application of such approaches. However, the difficulty to dissociate and isolate single cells from larval stages has been a major constraint to this kind of studies. Here, we describe an improved protocol for dissociation and preparation of single cell suspensions from developmentally synchronized populations of C. elegans L1 larvae. Our protocol has been empirically optimized to allow efficient FACS-based purification of large number of single cells from rare cell types, for subsequent extraction and sequencing of their mRNA.

RESUMEN

Directional migration of neurons and neuronal precursor cells is a central process in nervous system development. In the nematode Caenorhabditis elegans, the two Q neuroblasts polarize and migrate in opposite directions along the anteroposterior body axis. Several key regulators of Q cell polarization have been identified, including MIG-21, DPY-19/DPY19L1, the netrin receptor UNC-40/DCC, the Fat-like cadherin CDH-4 and CDH-3/Fat, which we describe in this study. How these different transmembrane proteins act together to direct Q neuroblast polarization and migration is still largely unknown. Here, we demonstrate that MIG-21 and DPY-19, CDH-3 and CDH-4, and UNC-40 define three distinct pathways that have partially redundant roles in protrusion formation, but also separate functions in regulating protrusion direction. Moreover, we show that the MIG-21, DPY-19 and Fat-like cadherin pathways control the localization and clustering of UNC-40 at the leading edge of the polarizing Q neuroblast, and that this is independent of the UNC-40 ligands UNC-6/netrin and MADD-4. Our results provide insight into a novel mechanism for ligand-independent localization of UNC-40 that directs the activity of UNC-40 along the anteroposterior axis.

Asunto(s)

Proteínas de Caenorhabditis elegans/metabolismo , Moléculas de Adhesión Celular/metabolismo , Polaridad Celular , Neuronas/citología , Neuronas/metabolismo , Animales , Caenorhabditis elegans/metabolismo , Movimiento Celular , Centrosoma/metabolismo , Ligandos , Transducción de Señal

RESUMEN

Appropriate Wnt morphogen secretion is required to control animal development and homeostasis. Although correct Wnt globular structure is essential for secretion, proteins that directly mediate Wnt folding and maturation remain uncharacterized. Here, we report that protein disulfide isomerase-1 (PDI-1), a protein-folding catalyst and chaperone, controls secretion of the Caenorhabditis elegans Wnt ortholog EGL-20. We find that PDI-1 function is required to correctly form an anteroposterior EGL-20/Wnt gradient during embryonic development. Furthermore, PDI-1 performs this role in EGL-20/Wnt-producing epidermal cells to cell-non-autonomously control EGL-20/Wnt-dependent neuronal migration. Using pharmacological inhibition, we further show that PDI function is required in human cells for Wnt3a secretion, revealing a conserved role for disulfide isomerases. Together, these results demonstrate a critical role for PDIs within Wnt-producing cells to control long-range developmental events that are dependent on Wnt secretion.

Asunto(s)

Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/metabolismo , Movimiento Celular , Neurogénesis , Neuronas/metabolismo , Proteína Disulfuro Isomerasas/metabolismo , Proteínas Wnt/metabolismo , Animales , Caenorhabditis elegans/citología , Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/genética , Células HEK293 , Humanos , Neuronas/citología , Proteína Disulfuro Isomerasas/genética , Proteínas Wnt/genética , Proteína Wnt3A/genética , Proteína Wnt3A/metabolismo

RESUMEN

Van Gogh-like (Vangl) and Prickle (Pk) are core components of the non-canonical Wnt planar cell polarity pathway that controls epithelial polarity and cell migration. Studies in vertebrate model systems have suggested that Vangl and Pk may also inhibit signaling through the canonical Wnt/ß-catenin pathway, but the functional significance of this potential cross-talk is unclear. In the nematode C. elegans, the Q neuroblasts and their descendants migrate in opposite directions along the anteroposterior body axis. The direction of these migrations is specified by Wnt signaling, with activation of canonical Wnt signaling driving posterior migration, and non-canonical Wnt signaling anterior migration. Here, we show that the Vangl ortholog VANG-1 influences the Wnt signaling response of the Q neuroblasts by negatively regulating canonical Wnt signaling. This inhibitory activity depends on a carboxy-terminal PDZ binding motif in VANG-1 and the Dishevelled ortholog MIG-5, but is independent of the Pk ortholog PRKL-1. Moreover, using Vangl1 and Vangl2 double mutant cells, we show that a similar mechanism acts in mammalian cells. We conclude that cross-talk between VANG-1/Vangl and the canonical Wnt pathway is an evolutionarily conserved mechanism that ensures robust specification of Wnt signaling responses.

Asunto(s)

Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/citología , Caenorhabditis elegans/metabolismo , Fosfoproteínas/metabolismo , Vía de Señalización Wnt/fisiología , Animales , Animales Modificados Genéticamente , Tipificación del Cuerpo/genética , Tipificación del Cuerpo/fisiología , Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/genética , Linaje de la Célula , Polaridad Celular/genética , Polaridad Celular/fisiología , Proteínas Dishevelled/genética , Proteínas Dishevelled/metabolismo , Genes de Helminto , Proteínas de Homeodominio/genética , Proteínas de Homeodominio/metabolismo , Péptidos y Proteínas de Señalización Intracelular/genética , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Mutación , Células-Madre Neurales/citología , Células-Madre Neurales/metabolismo , Fosfoproteínas/genética , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Vía de Señalización Wnt/genética , beta Catenina/genética , beta Catenina/metabolismo

RESUMEN

To advance our understanding of the genetic programs that drive cell and tissue specialization, it is necessary to obtain a comprehensive overview of gene expression patterns. Here, we have used spatial transcriptomics to generate high-resolution, anteroposterior gene expression maps of C. elegans males and hermaphrodites. To explore these maps, we have developed computational methods for discovering region- and tissue-specific genes. We have found extensive sex-specific gene expression differences in the germline and sperm and discovered genes that are specifically expressed in the male reproductive tract. These include a group of uncharacterized genes that encode small secreted proteins that are required for male fertility. We conclude that spatial gene expression maps provide a powerful resource for identifying tissue-specific gene functions in C. elegans. Importantly, we found that expression maps from different animals can be precisely aligned, enabling transcriptome-wide comparisons of gene expression patterns.

Asunto(s)

Perfilación de la Expresión Génica/métodos , Caracteres Sexuales , Procesos de Determinación del Sexo/genética , Transcriptoma/genética , Animales , Caenorhabditis elegans/genética , Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Diferenciación Celular , Trastornos del Desarrollo Sexual/genética , Femenino , Regulación del Desarrollo de la Expresión Génica/genética , Células Germinativas/metabolismo , Gónadas/metabolismo , Organismos Hermafroditas/metabolismo , Masculino , Meiosis , Proteínas Nucleares/metabolismo , Ovario/metabolismo , ARN Mensajero/genética , Análisis Espacio-Temporal , Espermatozoides/metabolismo , Factores de Transcripción/metabolismo

RESUMEN

Wntless transports Wnt morphogens to the cell surface and is required for Wnt secretion and morphogenic gradients formation. Recycling of endocytosed Wntless requires the sorting nexin-3 (SNX3)-retromer-dependent endosome-to-Golgi transport pathway. Here we demonstrate the essential role of SNX3-retromer assembly for Wntless transport and report that SNX3 associates with an evolutionary conserved endosome-associated membrane re-modelling complex composed of MON2, DOPEY2 and the putative aminophospholipid translocase, ATP9A. In vivo suppression of Ce-mon-2, Ce-pad-1 or Ce-tat-5 (respective MON2, DOPEY2 and ATP9A orthologues) phenocopy a loss of SNX3-retromer function, leading to enhanced lysosomal degradation of Wntless and a Wnt phenotype. Perturbed Wnt signalling is also observed upon overexpression of an ATPase-inhibited TAT-5(E246Q) mutant, suggesting a role for phospholipid flippase activity during SNX3-retromer-mediated Wntless sorting. Together, these findings provide in vitro and in vivo mechanistic details to describe SNX3-retromer-mediated transport during Wnt secretion and the formation of Wnt-morphogenic gradients.

Asunto(s)

Adenosina Trifosfatasas/metabolismo , Endosomas/metabolismo , Aparato de Golgi/metabolismo , Proteínas de Transporte de Membrana/metabolismo , Proteínas de Transferencia de Fosfolípidos/metabolismo , ATPasas de Translocación de Protón/metabolismo , Nexinas de Clasificación/metabolismo , Proteínas de Transporte Vesicular/metabolismo , Proteínas Wnt/metabolismo , Animales , Transporte Biológico , Caenorhabditis elegans , Proteínas Fluorescentes Verdes/metabolismo , Células HEK293 , Células HeLa , Humanos , Mutación , Fenotipo , Unión Proteica , Dominios Proteicos , Proteómica , Interferencia de ARN , Transgenes

RESUMEN

Important cellular processes such as migration, differentiation, and development often rely on precise timing. Yet, the molecular machinery that regulates timing is inherently noisy. How do cells achieve precise timing with noisy components? We investigate this question using a first-passage-time approach, for an event triggered by a molecule that crosses an abundance threshold and that is regulated by either an accumulating activator or a diminishing repressor. We find that either activation or repression outperforms an unregulated strategy. The optimal regulation corresponds to a nonlinear increase in the amount of the target molecule over time, arises from a tradeoff between minimizing the timing noise of the regulator and that of the target molecule itself, and is robust to additional effects such as bursts and cell division. Our results are in quantitative agreement with the nonlinear increase and low noise of mig-1 gene expression in migrating neuroblast cells during Caenorhabditis elegans development. These findings suggest that dynamic regulation may be a simple and powerful strategy for precise cellular timing.

Asunto(s)

Regulación del Desarrollo de la Expresión Génica/genética , Regulación del Desarrollo de la Expresión Génica/fisiología , Modelos Biológicos , Animales , Caenorhabditis elegans/citología , Caenorhabditis elegans/crecimiento & desarrollo , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Biología Computacional , Receptores Frizzled/genética , Receptores Frizzled/metabolismo , Neuronas/citología , Neuronas/fisiología , Factores de Tiempo

RESUMEN

Invertebrate and vertebrate nervous systems generate different types of dopaminergic neurons in distinct parts of the brain. We have taken a genetic approach to understand how the four functionally related, but lineally unrelated, classes of dopaminergic neurons of the nematode Caenorhabditis elegans, located in distinct parts of its nervous system, are specified. We have identified several genes involved in the generation of a specific dopaminergic neuron type that is generated from the so-called postdeirid lineage, called PDE. Apart from classic proneural genes and components of the mediator complex, we identified a novel, previously uncharacterized zinc finger transcription factor, ztf-6 Loss of ztf-6 has distinct effects in different dopamine neuron-producing neuronal lineages. In the postdeirid lineage, ztf-6 is required for proper cell division patterns and the proper distribution of a critical cell fate determinant, the POP-1/TCF-like transcription factor.

Asunto(s)

Proteínas de Caenorhabditis elegans/genética , Caenorhabditis elegans/metabolismo , Neuronas Dopaminérgicas/metabolismo , Regulación del Desarrollo de la Expresión Génica , Factores de Transcripción/genética , Dedos de Zinc , Secuencia de Aminoácidos , Animales , Caenorhabditis elegans/citología , Caenorhabditis elegans/crecimiento & desarrollo , Proteínas de Caenorhabditis elegans/metabolismo , Diferenciación Celular , División Celular , Linaje de la Célula/genética , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Dopamina/metabolismo , Neuronas Dopaminérgicas/clasificación , Neuronas Dopaminérgicas/citología , Proteínas del Grupo de Alta Movilidad/genética , Proteínas del Grupo de Alta Movilidad/metabolismo , Mutación , Factores de Transcripción/metabolismo

RESUMEN

During development, cell migration plays a central role in the formation of tissues and organs. Understanding the molecular mechanisms that drive and control these migrations is a key challenge in developmental biology that will provide important insights into disease processes, including cancer cell metastasis. In this article, we discuss the Caenorhabditis elegans Q neuroblasts and their descendants as a tool to study cell migration at single-cell resolution in vivo. The highly stereotypical migration of these cells provides a powerful system to study the dynamic cytoskeletal processes that drive migration as well as the evolutionarily conserved signaling pathways (including different Wnt signaling cascades) that guide the cells along their specific trajectories. Here, we provide an overview of what is currently known about Q neuroblast migration and highlight the live-cell imaging, genome editing, and quantitative gene expression techniques that have been developed to study this process.

Asunto(s)

Blástula/citología , Caenorhabditis elegans/crecimiento & desarrollo , Células-Madre Neurales/citología , Análisis de la Célula Individual/métodos , Animales , Caenorhabditis elegans/genética , Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Movimiento Celular , Polaridad Celular , Edición Génica , Regulación del Desarrollo de la Expresión Génica , Modelos Biológicos , Transducción de Señal

RESUMEN

The biogenesis of ribosomes and their coordination of protein translation consume an enormous amount of cellular energy. As such, it has been established that the inhibition of either process can extend eukaryotic lifespan. Here, we used next-generation sequencing to compare ribosome-associated RNAs from normal strains of Caenorhabditis elegans to those carrying the life-extending daf-2 mutation. We found a long noncoding RNA (lncRNA), transcribed telomeric sequence 1 (tts-1), on ribosomes of the daf-2 mutant. Depleting tts-1 in daf-2 mutants increases ribosome levels and significantly shortens their extended lifespan. We find tts-1 is also required for the longer lifespan of the mitochondrial clk-1 mutants but not the feeding-defective eat-2 mutants. In line with this, the clk-1 mutants express more tts-1 and fewer ribosomes than the eat-2 mutants. Our results suggest that the expression of tts-1 functions in different longevity pathways to reduce ribosome levels in a way that promotes life extension.

RESUMEN

Members of the Wnt family of secreted signaling proteins are key regulators of cell migration and axon guidance. In the nematode C. elegans, the migration of the QR neuroblast descendants requires multiple Wnt ligands and receptors. We found that the migration of the QR descendants is divided into three sequential phases that are each mediated by a distinct Wnt signaling mechanism. Importantly, the transition from the first to the second phase, which is the main determinant of the final position of the QR descendants along the anteroposterior body axis, is mediated through a cell-autonomous process in which the time-dependent expression of a Wnt receptor turns on the canonical Wnt/ß-catenin signaling response that is required to terminate long-range anterior migration. Our results show that, in addition to direct guidance of cell migration by Wnt morphogenic gradients, cell migration can also be controlled indirectly through cell-intrinsic modulation of Wnt signaling responses.

Asunto(s)

Caenorhabditis elegans/crecimiento & desarrollo , Movimiento Celular/genética , Células-Madre Neurales/fisiología , Proteínas Wnt/metabolismo , Vía de Señalización Wnt/genética , Animales , Caenorhabditis elegans/citología , Proteínas de Caenorhabditis elegans/biosíntesis , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Polaridad Celular , Receptores Frizzled/biosíntesis , Receptores Frizzled/metabolismo , Regulación de la Expresión Génica/genética , Glicoproteínas/biosíntesis , Glicoproteínas/genética , Glicoproteínas/metabolismo , Proteínas de Homeodominio/genética , Péptidos y Proteínas de Señalización Intracelular/biosíntesis , Péptidos y Proteínas de Señalización Intracelular/genética , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Morfogénesis , Células-Madre Neurales/citología , Fosfoproteínas/metabolismo , Receptores Huérfanos Similares al Receptor Tirosina Quinasa/genética , Receptores Huérfanos Similares al Receptor Tirosina Quinasa/metabolismo , Receptores Acoplados a Proteínas G/biosíntesis , Factores de Transcripción/genética , Proteínas Wnt/biosíntesis , beta Catenina/metabolismo

RESUMEN

During the first stage of larval development, the Q neuroblasts and their descendants migrate to well-defined positions along the anteroposterior body axis, where they differentiate into sensory neurons and interneurons. The two Q neuroblasts are initially present at similar positions on the left and right lateral side, but this symmetry is broken when the Q neuroblast on the left side (QL) polarizes towards the posterior and the Q neuroblast on the right side (QR) towards the anterior. This left-right asymmetry is maintained when the descendants of the two Q neuroblasts migrate to their final positions in the posterior and anterior. The mechanisms that establish this asymmetry and control the migration of the Q descendants along the anteroposterior axis are surprisingly complex and include interplay between Wnt signaling pathways, homeotic genes, and the basic cell migration and polarity machinery. Here, we will give an overview of what is currently known about the mechanisms that mediate and control the development and migration of the Q neuroblasts and their descendants.

Asunto(s)

Caenorhabditis elegans/citología , Movimiento Celular , Células-Madre Neurales/citología , Animales , Tipificación del Cuerpo , Caenorhabditis elegans/embriología