RESUMEN
Highly potent adult stem cells fuel lifelong tissue homeostasis and regeneration in many aquatic invertebrates, yet their developmental backstories remain obscure. In this issue of Cell, Kimura and colleagues reveal the cellular origin of adult pluripotent stem cells and propose a molecular trajectory for their specification during acoel embryogenesis.
Asunto(s)
Células Madre Adultas , Células Madre Pluripotentes , Animales , Desarrollo Embrionario , Invertebrados , Homeostasis , Diferenciación CelularRESUMEN
Glia play multifaceted roles in nervous systems in response to injury. Depending on the species, extent of injury and glial cell type in question, glia can help or hinder the regeneration of neurons. Studying glia in the context of successful regeneration could reveal features of pro-regenerative glia that could be exploited for new human therapies. Planarian flatworms completely regenerate their nervous systems after injury - including glia - and thus provide a strong model system for exploring glia in the context of regeneration. Here, we report that planarian glia regenerate after neurons, and that neurons are required for correct glial numbers and localization during regeneration. We also identify the planarian transcription factor-encoding gene ets-1 as a key regulator of glial cell maintenance and regeneration. Using ets-1 (RNAi) to perturb glia, we show that glial loss is associated with altered neuronal gene expression, impeded animal movement and impaired nervous system architecture - particularly within the neuropil. Importantly, our work reveals the inter-relationships of glia and neurons in the context of robust neural regeneration.
Asunto(s)
Planarias , Animales , Humanos , Planarias/genética , Proteína Proto-Oncogénica c-ets-1/genética , Neuroglía , Neuronas , NeurópiloRESUMEN
As the planarian research community expands, the need for an interoperable data organization framework for tool building has become increasingly apparent. Such software would streamline data annotation and enhance cross-platform and cross-species searchability. We created the Planarian Anatomy Ontology (PLANA), an extendable relational framework of defined Schmidtea mediterranea (Smed) anatomical terms used in the field. At publication, PLANA contains over 850 terms describing Smed anatomy from subcellular to system levels across all life cycle stages, in intact animals and regenerating body fragments. Terms from other anatomy ontologies were imported into PLANA to promote interoperability and comparative anatomy studies. To demonstrate the utility of PLANA as a tool for data curation, we created resources for planarian embryogenesis, including a staging series and molecular fate-mapping atlas, and the Planarian Anatomy Gene Expression database, which allows retrieval of a variety of published transcript/gene expression data associated with PLANA terms. As an open-source tool built using FAIR (findable, accessible, interoperable, reproducible) principles, our strategy for continued curation and versioning of PLANA also provides a platform for community-led growth and evolution of this resource.
Asunto(s)
Planarias/anatomía & histología , Planarias/genética , Animales , Desarrollo Embrionario/genética , Regulación del Desarrollo de la Expresión Génica/genética , Ontología de Genes , Estadios del Ciclo de Vida/genética , Regeneración/genética , Programas InformáticosRESUMEN
Specialized microenvironments, or niches, provide signaling cues that regulate stem cell behavior. In the Drosophila testis, the JAK-STAT signaling pathway regulates germline stem cell (GSC) attachment to the apical hub and somatic cyst stem cell (CySC) identity. Here, we demonstrate that chickadee, the Drosophila gene that encodes profilin, is required cell autonomously to maintain GSCs, possibly facilitating localization or maintenance of E-cadherin to the GSC-hub cell interface. Germline specific overexpression of Adenomatous Polyposis Coli 2 (APC2) rescued GSC loss in chic hypomorphs, suggesting an additive role of APC2 and F-actin in maintaining the adherens junctions that anchor GSCs to the niche. In addition, loss of chic function in the soma resulted in failure of somatic cyst cells to maintain germ cell enclosure and overproliferation of transit-amplifying spermatogonia.
Asunto(s)
Proteínas de Drosophila/metabolismo , Drosophila melanogaster/metabolismo , Profilinas/metabolismo , Espermatozoides/metabolismo , Células Madre/metabolismo , Proteínas Supresoras de Tumor/metabolismo , Actinas/metabolismo , Uniones Adherentes/metabolismo , Animales , Cadherinas/metabolismo , Diferenciación Celular , Linaje de la Célula , Proliferación Celular , Proteínas de Drosophila/biosíntesis , Proteínas de Drosophila/genética , Drosophila melanogaster/citología , Regulación del Desarrollo de la Expresión Génica , Masculino , Profilinas/genética , Unión Proteica , Interferencia de ARN , ARN Interferente Pequeño/genética , Transducción de Señal/genética , Espermatogonias/citología , Espermatogonias/metabolismo , Espermatozoides/citología , Nicho de Células Madre , Proteínas Supresoras de Tumor/biosíntesisRESUMEN
Stem cell behavior is regulated by extrinsic signals from specialized microenvironments, or niches, and intrinsic factors required for execution of context-appropriate responses to niche signals. Here we show that function of the transcriptional regulator longitudinals lacking (lola) is required cell autonomously for germline stem cell and somatic cyst stem cell maintenance in the Drosophila testis. In addition, lola is also required for proper execution of key developmental transitions during male germ cell differentiation, including the switch from transit amplifying progenitor to spermatocyte growth and differentiation, as well as meiotic cell cycle progression and spermiogenesis. Different lola isoforms, each having unique C-termini and zinc finger domains, may control different aspects of proliferation and differentiation in the male germline and somatic cyst stem cell lineages.
Asunto(s)
Diferenciación Celular , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/citología , Drosophila melanogaster/genética , Espermatozoides/citología , Células Madre/citología , Testículo/citología , Factores de Transcripción/metabolismo , Animales , Diferenciación Celular/genética , División Celular , Linaje de la Célula/genética , Proteínas de Drosophila/genética , Regulación del Desarrollo de la Expresión Génica , Técnicas de Silenciamiento del Gen , Quinasas Janus/metabolismo , Masculino , Meiosis , Mutación/genética , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Interferencia de ARN , Factores de Transcripción STAT/metabolismo , Transducción de Señal , Espermatogénesis/genética , Espermatogonias/citología , Espermatogonias/metabolismo , Espermatozoides/metabolismo , Células Madre/metabolismo , Factores de Transcripción/genética , Factor de Crecimiento Transformador beta/metabolismoRESUMEN
Post-translational modifications provide sensitive and flexible mechanisms to dynamically modulate protein function in response to specific signalling inputs. In the case of transcription factors, changes in phosphorylation state can influence protein stability, conformation, subcellular localization, cofactor interactions, transactivation potential and transcriptional output. Here we show that the evolutionarily conserved transcription factor Eyes absent (Eya) belongs to the phosphatase subgroup of the haloacid dehalogenase (HAD) superfamily, and propose a function for it as a non-thiol-based protein tyrosine phosphatase. Experiments performed in cultured Drosophila cells and in vitro indicate that Eyes absent has intrinsic protein tyrosine phosphatase activity and can autocatalytically dephosphorylate itself. Confirming the biological significance of this function, mutations that disrupt the phosphatase active site severely compromise the ability of Eyes absent to promote eye specification and development in Drosophila. Given the functional importance of phosphorylation-dependent modulation of transcription factor activity, this evidence for a nuclear transcriptional coactivator with intrinsic phosphatase activity suggests an unanticipated method of fine-tuning transcriptional regulation.
Asunto(s)
Proteínas de Drosophila/metabolismo , Drosophila melanogaster/enzimología , Proteínas del Ojo/metabolismo , Proteínas Tirosina Fosfatasas/metabolismo , Factores de Transcripción/metabolismo , Secuencias de Aminoácidos , Secuencia de Aminoácidos , Animales , Anticuerpos Fosfo-Específicos/inmunología , Proteínas de Drosophila/química , Proteínas de Drosophila/genética , Drosophila melanogaster/embriología , Drosophila melanogaster/genética , Inducción Embrionaria , Ojo/embriología , Ojo/enzimología , Ojo/metabolismo , Proteínas del Ojo/química , Proteínas del Ojo/genética , Regulación de la Expresión Génica , Cinética , Ratones , Modelos Moleculares , Datos de Secuencia Molecular , Mutación/genética , Fosforilación , Conformación Proteica , Proteínas Tirosina Fosfatasas/química , Proteínas Tirosina Fosfatasas/genética , Especificidad por Sustrato , Factores de Transcripción/química , Factores de Transcripción/genéticaRESUMEN
The retinal determination (RD) gene network encodes a group of transcription factors and cofactors necessary for eye development. Transcriptional and posttranslational regulation of RD family members is achieved through interactions within the network and with extracellular signaling pathways, including epidermal growth factor receptor/RAS/mitogen-activated protein kinase (MAPK), transforming growth factor beta/DPP, Wingless, Hedgehog, and Notch. Here we present the results of structure-function analyses that reveal novel aspects of Eyes absent (EYA) function and regulation. We find that the conserved C-terminal EYA domain negatively regulates EYA transactivation potential, and that GROUCHO-SINE OCULIS (SO) interactions provide another mechanism for negative regulation of EYA-SO target genes. We have mapped the transactivation potential of EYA to an internal proline-, serine-, and threonine-rich region that includes the EYA domain 2 (ED2) and two MAPK phosphorylation consensus sites and demonstrate that activation of the RAS/MAPK pathway potentiates transcriptional output of EYA and the EYA-SO complex in certain contexts. Drosophila S2 cell two-hybrid assays were used to describe a novel homotypic interaction that is mediated by EYA's N terminus. Our data suggest that EYA requires homo- and heterotypic interactions and RAS/MAPK signaling responsiveness to ensure context-appropriate RD gene network activity.
Asunto(s)
Proteínas de Drosophila/metabolismo , Proteínas del Ojo/metabolismo , Retina/fisiología , Animales , Animales Modificados Genéticamente , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico , Células Cultivadas , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Drosophila/genética , Proteínas de Drosophila/genética , Proteínas del Ojo/genética , Regulación del Desarrollo de la Expresión Génica , Proteínas de Homeodominio/genética , Proteínas de Homeodominio/metabolismo , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Mutación , Fosforilación , Estructura Terciaria de Proteína , Secuencias Reguladoras de Ácidos Nucleicos , Proteínas Represoras/genética , Proteínas Represoras/metabolismo , Transducción de Señal , Relación Estructura-Actividad , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Transcripción Genética , Activación Transcripcional , Técnicas del Sistema de Dos Híbridos , Proteínas ras/genética , Proteínas ras/metabolismoRESUMEN
Planarian neoblasts are pluripotent, adult somatic stem cells and lineage-primed progenitors that are required for the production and maintenance of all differentiated cell types, including the germline. Neoblasts, originally defined as undifferentiated cells residing in the adult parenchyma, are frequently compared to embryonic stem cells yet their developmental origin remains obscure. We investigated the provenance of neoblasts during Schmidtea mediterranea embryogenesis, and report that neoblasts arise from an anarchic, cycling piwi-1+ population wholly responsible for production of all temporary and definitive organs during embryogenesis. Early embryonic piwi-1+ cells are molecularly and functionally distinct from neoblasts: they express unique cohorts of early embryo enriched transcripts and behave differently than neoblasts in cell transplantation assays. Neoblast lineages arise as organogenesis begins and are required for construction of all major organ systems during embryogenesis. These subpopulations are continuously generated during adulthood, where they act as agents of tissue homeostasis and regeneration.