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1.
PLoS Genet ; 20(3): e1010899, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38517900

RESUMO

Tissues are subject to multiple mechanical inputs at the cellular level that influence their overall shape and function. In the small intestine, actomyosin contractility can be induced by many physiological and pathological inputs. However, we have little understanding of how contractility impacts the intestinal epithelium on a cellular and tissue level. In this study, we probed the cell and tissue-level effects of contractility by using mouse models to genetically increase the level of myosin activity in the two distinct morphologic compartments of the intestinal epithelium, the crypts and villi. We found that increased contractility in the villar compartment caused shape changes in the cells that expressed the transgene and their immediate neighbors. While there were no discernable effects on villar architecture or cell polarity, even low levels of transgene induction in the villi caused non-cell autonomous hyperproliferation of the transit amplifying cells in the crypt, driving increased cell flux through the crypt-villar axis. In contrast, induction of increased contractility in the proliferating cells of the crypts resulted in nuclear deformations, DNA damage, and apoptosis. This study reveals the complex and diverse responses of different intestinal epithelial cells to contractility and provides important insight into mechanical regulation of intestinal physiology.


Assuntos
Mucosa Intestinal , Intestinos , Camundongos , Animais , Mucosa Intestinal/patologia , Intestino Delgado , Células Epiteliais , Epitélio
2.
bioRxiv ; 2023 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-37609300

RESUMO

Tissues are subject to multiple mechanical inputs at the cellular level that influence their overall shape and function. In the small intestine, actomyosin contractility can be induced by many physiological and pathological inputs. However, we have little understanding of how contractility impacts the intestinal epithelium on a cellular and tissue level. In this study, we probed the cell and tissue-level effects of contractility by using mouse models to genetically increase the level of myosin activity in the two distinct morphologic compartments of the intestinal epithelium, the crypts and villi. We found that increased contractility in the villar compartment caused shape changes in the cells that expressed the transgene and their immediate neighbors. While there were no discernable effects on villar architecture, even low levels of transgene induction in the villi caused non-cell autonomous hyperproliferation of the transit amplifying cells in the crypt, driving increased cell flux through the crypt-villar axis. In contrast, induction of increased contractility in the proliferating cells of the crypts resulted in nuclear deformations, DNA damage, and apoptosis. This study reveals the complex and diverse responses of different intestinal epithelial cells to contractility and provides important insight into mechanical regulation of intestinal physiology.

3.
Curr Top Dev Biol ; 154: 317-336, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37100522

RESUMO

The epidermis is a stratified squamous epithelium that forms the outermost layer of the skin. Its primary function is to act as a barrier, keeping pathogens and toxins out and moisture in. This physiological role has necessitated major differences in the organization and polarity of the tissue as compared to simple epithelia. We discuss four aspects of polarity in the epidermis - the distinctive polarities of basal progenitor cells as well as differentiated granular cells, the polarity of adhesions and the cytoskeleton across the tissue as keratinocytes differentiate, and the planar cell polarity of the tissue. These distinctive polarities are essential for the morphogenesis and the function of the epidermis and have also been implicated in regulating tumor formation.


Assuntos
Epiderme , Neoplasias , Humanos , Epiderme/fisiologia , Epitélio , Pele , Células Epidérmicas , Polaridade Celular
4.
Development ; 149(23)2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36504079

RESUMO

There are fundamental differences in how neonatal and adult intestines absorb nutrients. In adults, macromolecules are broken down into simpler molecular components in the lumen of the small intestine, then absorbed. In contrast, neonates are thought to rely on internalization of whole macromolecules and subsequent degradation in the lysosome. Here, we identify the Maf family transcription factors MAFB and c-MAF as markers of terminally differentiated intestinal enterocytes throughout life. The expression of these factors is regulated by HNF4α and HNF4γ, master regulators of enterocyte cell fate. Loss of Maf factors results in a neonatal-specific failure to thrive and loss of macromolecular nutrient uptake. RNA-Seq and CUT&RUN analyses defined an endo-lysosomal program as being downstream of these transcription factors. We demonstrate major transcriptional changes in metabolic pathways, including fatty acid oxidation and increases in peroxisome number, in response to loss of Maf proteins. Finally, we show that loss of BLIMP1, a repressor of adult enterocyte genes, shows highly overlapping changes in gene expression and similar defects in macromolecular uptake. This work defines transcriptional regulators that are necessary for nutrient uptake in neonatal enterocytes.


Assuntos
Fatores de Transcrição Maf , Nutrientes , Camundongos , Animais , Transporte Biológico , Diferenciação Celular , Fatores de Transcrição/genética , Proteínas Proto-Oncogênicas c-maf
5.
Cell Stem Cell ; 29(1): 1-2, 2022 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-34995491

RESUMO

The number of hair follicle stem cells decreases during aging and in hair-loss disorders, such as alopecia. In this issue of Cell Stem Cell, Xie et al. (2021) discover that the hair shaft serves as a physical niche component for the preservation of hair follicle stem cells.


Assuntos
Alopecia , Folículo Piloso , Envelhecimento , Cabelo , Humanos , Células-Tronco
6.
Mol Biol Cell ; 32(21): ar29, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34432485

RESUMO

Proper spindle orientation is required for asymmetric cell division and the establishment of complex tissue architecture. In the developing epidermis, spindle orientation requires a conserved cortical protein complex of LGN/NuMA/dynein-dynactin. However, how microtubule dynamics are regulated to interact with this machinery and properly position the mitotic spindle is not fully understood. Furthermore, our understanding of the processes that link spindle orientation during asymmetric cell division to cell fate specification in distinct tissue contexts remains incomplete. We report a role for the microtubule catastrophe factor KIF18B in regulating microtubule dynamics to promote spindle orientation in keratinocytes. During mitosis, KIF18B accumulates at the cell cortex, colocalizing with the conserved spindle orientation machinery. In vivo we find that KIF18B is required for oriented cell divisions within the hair placode, the first stage of hair follicle morphogenesis, but is not essential in the interfollicular epidermis. Disrupting spindle orientation in the placode, using mutations in either KIF18B or NuMA, results in aberrant cell fate marker expression of hair follicle progenitor cells. These data functionally link spindle orientation to cell fate decisions during hair follicle morphogenesis. Taken together, our data demonstrate a role for regulated microtubule dynamics in spindle orientation in epidermal cells. This work also highlights the importance of spindle orientation during asymmetric cell division to dictate cell fate specification.


Assuntos
Cinesinas/metabolismo , Microtúbulos/fisiologia , Fuso Acromático/fisiologia , Animais , Complexo Dinactina/metabolismo , Dineínas/metabolismo , Células Epidérmicas/metabolismo , Epiderme/metabolismo , Feminino , Queratinócitos/metabolismo , Cinesinas/fisiologia , Masculino , Camundongos , Camundongos Knockout , Microtúbulos/metabolismo , Mitose , Cultura Primária de Células , Fuso Acromático/metabolismo
7.
Mol Biol Cell ; 32(20): ar2, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34319758

RESUMO

Keratin intermediate filaments form dynamic polymer networks that organize in specific ways dependent on the cell type, the stage of the cell cycle, and the state of the cell. In differentiated cells of the epidermis, they are organized by desmosomes, cell-cell adhesion complexes that provide essential mechanical integrity to this tissue. Despite this, we know little about how keratin organization is controlled and whether desmosomes locally regulate keratin dynamics in addition to binding preassembled filaments. Ndel1 is a desmosome-associated protein in the differentiated epidermis, though its function at these structures has not been examined. Here, we show that Ndel1 binds directly to keratin subunits through a motif conserved in all intermediate filament proteins. Further, Ndel1 was necessary for robust desmosome-keratin association and sufficient to reorganize keratins at distinct cellular sites. Lis1, a Ndel1 binding protein, was required for desmosomal localization of Ndel1, but not for its effects on keratin filaments. Finally, we use mouse genetics to demonstrate that loss of Ndel1 results in desmosome defects in the epidermis. Our data thus identify Ndel1 as a desmosome-associated protein that promotes local assembly/reorganization of keratin filaments and is essential for robust desmosome formation.


Assuntos
Proteínas de Transporte/metabolismo , Desmossomos/metabolismo , Queratinas/metabolismo , 1-Alquil-2-acetilglicerofosfocolina Esterase/metabolismo , Animais , Adesão Celular/fisiologia , Diferenciação Celular , Células Cultivadas , Citoesqueleto/metabolismo , Desmoplaquinas/metabolismo , Células Epidérmicas/metabolismo , Epiderme/metabolismo , Filamentos Intermediários/metabolismo , Queratinócitos/metabolismo , Camundongos , Proteínas Associadas aos Microtúbulos/metabolismo
8.
Nat Rev Mol Cell Biol ; 22(10): 691-708, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34158639

RESUMO

In multicellular systems, oriented cell divisions are essential for morphogenesis and homeostasis as they determine the position of daughter cells within the tissue and also, in many cases, their fate. Early studies in invertebrates led to the identification of conserved core mechanisms of mitotic spindle positioning centred on the Gαi-LGN-NuMA-dynein complex. In recent years, much has been learnt about the way this complex functions in vertebrate cells. In particular, studies addressed how the Gαi-LGN-NuMA-dynein complex dynamically crosstalks with astral microtubules and the actin cytoskeleton, and how it is regulated to orient the spindle according to cellular and tissue-wide cues. We have also begun to understand how dynein motors and actin regulators interact with mechanosensitive adhesion molecules sensing extracellular mechanical stimuli, such as cadherins and integrins, and with signalling pathways so as to respond to extracellular cues instructing the orientation of the division axis in vivo. In this Review, with the focus on epithelial tissues, we discuss the molecular mechanisms of mitotic spindle orientation in vertebrate cells, and how this machinery is regulated by epithelial cues and extracellular signals to maintain tissue cohesiveness during mitosis. We also outline recent knowledge of how spindle orientation impacts tissue architecture in epithelia and its emerging links to the regulation of cell fate decisions. Finally, we describe how defective spindle orientation can be corrected or its effects eliminated in tissues under physiological conditions, and the pathological implications associated with spindle misorientation.


Assuntos
Fuso Acromático/metabolismo , Citoesqueleto de Actina/metabolismo , Animais , Diferenciação Celular , Polaridade Celular , Células Epiteliais/citologia , Células Epiteliais/metabolismo , Epitélio/metabolismo , Humanos , Mitose , Transdução de Sinais
9.
Cell Stem Cell ; 28(3): 436-452.e5, 2021 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-33264636

RESUMO

Basal stem cells fuel development, homeostasis, and regeneration of the epidermis. The proliferation and fate decisions of these cells are highly regulated by their microenvironment, including the basement membrane and underlying mesenchymal cells. Basal progenitors give rise to differentiated progeny that generate the epidermal barrier. Here, we present data that differentiated progeny also regulate the proliferation, differentiation, and migration of basal progenitor cells. Using two distinct mouse lines, we found that increasing contractility of differentiated cells resulted in non-cell-autonomous hyperproliferation of stem cells and prevented their commitment to a hair follicle lineage. This increased contractility also impaired movement of basal progenitors during hair placode morphogenesis and diminished migration of melanoblasts. These data suggest that intra-tissue tension regulates stem cell proliferation, fate decisions, and migration and that differentiated epidermal keratinocytes are a component of the stem cell niche that regulates development and homeostasis of the skin.


Assuntos
Células Epidérmicas , Células-Tronco , Animais , Diferenciação Celular , Proliferação de Células , Epiderme , Folículo Piloso , Queratinócitos , Camundongos
10.
Curr Opin Cell Biol ; 68: 98-104, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33186891

RESUMO

While microtubule dynamics and organization have been extensively studied invitro, both biochemically and in cultured cells, recent work has begun to extend this into tissues ex vivo and organisms in vivo. Advances in genetic tools and imaging technology have allowed studies on the dynamics, function, and organization of microtubules in the stratified epithelia of the epidermis. Here, we discuss recent work that highlights the varied roles that microtubules play in supporting epidermal function. These findings demonstrate that studying microtubules in tissues has revealed not only novel aspects of epidermal biology but also new principles of microtubule regulation.


Assuntos
Células Epidérmicas/citologia , Microtúbulos/fisiologia , Pele/citologia , Animais , Diferenciação Celular , Centrossomo/fisiologia , Cílios/metabolismo , Humanos , Queratinócitos/citologia , Transdução de Sinais
11.
Development ; 147(20)2020 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-32994164

RESUMO

Between embryonic days 10.5 and 14.5, active proliferation drives rapid elongation of the murine midgut epithelial tube. Within this pseudostratified epithelium, nuclei synthesize DNA near the basal surface and move apically to divide. After mitosis, the majority of daughter cells extend a long, basally oriented filopodial protrusion, building a de novo path along which their nuclei can return to the basal side. WNT5A, which is secreted by surrounding mesenchymal cells, acts as a guidance cue to orchestrate this epithelial pathfinding behavior, but how this signal is received by epithelial cells is unknown. Here, we have investigated two known WNT5A receptors: ROR2 and RYK. We found that epithelial ROR2 is dispensable for midgut elongation. However, loss of Ryk phenocopies the Wnt5a-/- phenotype, perturbing post-mitotic pathfinding and leading to apoptosis. These studies reveal that the ligand-receptor pair WNT5A-RYK acts as a navigation system to instruct filopodial pathfinding, a process that is crucial for continuous cell cycling to fuel rapid midgut elongation.


Assuntos
Sistema Digestório/crescimento & desenvolvimento , Sistema Digestório/metabolismo , Pseudópodes/metabolismo , Receptores Proteína Tirosina Quinases/metabolismo , Animais , Apoptose , Núcleo Celular/metabolismo , Células Epiteliais/citologia , Células Epiteliais/metabolismo , Epitélio/metabolismo , Feminino , Masculino , Mesoderma/metabolismo , Camundongos Endogâmicos C57BL , Receptores Órfãos Semelhantes a Receptor Tirosina Quinase/metabolismo
12.
Mol Biol Cell ; 31(11): 1140-1153, 2020 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-32238101

RESUMO

Desmosomes are cell-cell adhesions necessary for the maintenance of tissue integrity in the skin and heart. While the core components of desmosomes have been identified, peripheral components that modulate canonical or noncanonical desmosome functions still remain largely unexplored. Here we used targeted proximity labeling approaches to further elaborate the desmosome proteome in epidermal keratinocytes. Quantitative mass spectrometry analysis identified all core desmosomal proteins while uncovering a diverse array of new constituents with broad molecular functions. By individually targeting the inner and outer dense plaques, we defined proteins enriched within these subcompartments. We validated a number of these novel desmosome-associated proteins and find that many are membrane proximal proteins that show a dependence on functional desmosomes for their cortical localization. We further explored the mechanism of localization and function of two novel desmosome-associated adaptor proteins enriched in the desmosome proteome, Crk and Crk-like (CrkL). These proteins interacted with Dsg1 and rely on Dsg1 and desmoplakin for robust cortical localization. Epidermal deletion of both Crk and CrkL resulted in perinatal lethality with defects in desmosome morphology and keratin organization, thus demonstrating the utility of this dataset in identifying novel proteins required for desmosome-dependent epidermal integrity.


Assuntos
Desmossomos/metabolismo , Epiderme/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Animais , Adesão Celular , Citoesqueleto/metabolismo , Desmoplaquinas/metabolismo , Desmossomos/fisiologia , Células Epidérmicas/metabolismo , Células Epidérmicas/fisiologia , Epiderme/fisiologia , Humanos , Queratinócitos/metabolismo , Queratinas/metabolismo , Masculino , Espectrometria de Massas/métodos , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Proteômica/métodos , Proteínas Proto-Oncogênicas c-crk/metabolismo , Pele/metabolismo
13.
Curr Biol ; 30(4): R144-R149, 2020 02 24.
Artigo em Inglês | MEDLINE | ID: mdl-32097634

RESUMO

In this Primer, Moreci and Lechler follow the lifetime of an epidermal cell from its birth to its ultimate death, and detail how this journey is necessary for epidermal function.


Assuntos
Diferenciação Celular , Células Epidérmicas/fisiologia , Epiderme/fisiologia , Animais , Epiderme/crescimento & desenvolvimento
14.
Elife ; 82019 10 02.
Artigo em Inglês | MEDLINE | ID: mdl-31577227

RESUMO

Tissue homeostasis requires a balance between progenitor cell proliferation and loss. Mechanisms that maintain this robust balance are needed to avoid tissue loss or overgrowth. Here we demonstrate that regulation of spindle orientation/asymmetric cell divisions is one mechanism that is used to buffer changes in proliferation and tissue turnover in mammalian skin. Genetic and pharmacologic experiments demonstrate that asymmetric cell divisions were increased in hyperproliferative conditions and decreased under hypoproliferative conditions. Further, active K-Ras also increased the frequency of asymmetric cell divisions. Disruption of spindle orientation in combination with constitutively active K-Ras resulted in massive tissue overgrowth. Together, these data highlight the essential roles of spindle orientation in buffering tissue homeostasis in response to perturbations.


Assuntos
Divisão Celular Assimétrica/genética , Divisão Celular/genética , Proliferação de Células/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Animais , Polaridade Celular/genética , Células Epidérmicas/metabolismo , Epiderme/crescimento & desenvolvimento , Epiderme/metabolismo , Homeostase/genética , Camundongos , Pele/crescimento & desenvolvimento , Pele/metabolismo , Fuso Acromático , Células-Tronco/citologia , Células-Tronco/metabolismo
15.
Dev Cell ; 51(1): 7-20.e6, 2019 10 07.
Artigo em Inglês | MEDLINE | ID: mdl-31474562

RESUMO

The guts of neonatal mammals and stomachless fish have a limited capacity for luminal protein digestion, which allows oral acquisition of antibodies and antigens. However, how dietary protein is absorbed during critical developmental stages when the gut is still immature is unknown. Here, we show that specialized intestinal cells, which we call lysosome-rich enterocytes (LREs), internalize dietary protein via receptor-mediated and fluid-phase endocytosis for intracellular digestion and trans-cellular transport. In LREs, we identify a conserved endocytic machinery, composed of the scavenger receptor complex Cubilin/Amnionless and Dab2, that is required for protein uptake by LREs and for growth and survival of larval zebrafish. Moreover, impairing LRE function in suckling mice, via conditional deletion of Dab2, leads to stunted growth and severe protein malnutrition reminiscent of kwashiorkor, a devastating human malnutrition syndrome. These findings identify digestive functions and conserved molecular mechanisms in LREs that are crucial for vertebrate growth and survival.


Assuntos
Proteínas Alimentares/metabolismo , Enterócitos/metabolismo , Absorção Intestinal , Intestinos/embriologia , Lisossomos/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas Adaptadoras de Transporte Vesicular/metabolismo , Animais , Proteínas Reguladoras de Apoptose/metabolismo , Modelos Animais de Doenças , Feminino , Microbioma Gastrointestinal , Deleção de Genes , Regulação da Expressão Gênica no Desenvolvimento , Íleo/embriologia , Íleo/metabolismo , Kwashiorkor/metabolismo , Ligantes , Masculino , Proteínas de Membrana/metabolismo , Camundongos , Receptores de Superfície Celular/metabolismo , Peixe-Zebra , Proteínas de Peixe-Zebra/metabolismo
16.
Dev Cell ; 46(2): 127-128, 2018 07 16.
Artigo em Inglês | MEDLINE | ID: mdl-30016614

RESUMO

During embryonic development, the midgut needs to undergo extensive elongation to form the small intestine. In this issue of Development Cell, Wang et. al. (2018) explore the cell dynamics of this tissue and find that regulated re-integration of cells into the epithelial layer is important for elongation.


Assuntos
Sistema Digestório , Endoderma , Células Epiteliais , Feminino , Humanos , Gravidez
17.
Mol Biol Cell ; 29(13): 1533-1541, 2018 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-29742015

RESUMO

In most differentiated cells, microtubules reorganize into noncentrosomal arrays that are cell-type specific. In the columnar absorptive enterocytes of the intestine, microtubules form polarized apical-basal arrays that have been proposed to play multiple roles. However, in vivo testing of these hypotheses has been hampered by a lack of genetic tools to specifically perturb microtubules. Here we analyze mice in which microtubules are disrupted by conditional inducible expression of the microtubule-severing protein spastin. Spastin overexpression resulted in multiple cellular defects, including aberrations in nuclear and organelle positioning and deficient nutrient transport. However, cell shape, adhesion, and polarity remained intact, and mutant mice continued to thrive. Notably, the phenotypes of microtubule disruption are similar to those induced by microtubule disorganization upon loss of CAMSAP3/Nezha. These data demonstrate that enterocyte microtubules have important roles in organelle organization but are not essential for growth under homeostatic conditions.


Assuntos
Intestinos/fisiologia , Espaço Intracelular/metabolismo , Microtúbulos/metabolismo , Animais , Transporte Biológico , Diferenciação Celular , Centrossomo/metabolismo , Enterócitos/metabolismo , Mucosa Intestinal/metabolismo , Camundongos Knockout , Proteínas Associadas aos Microtúbulos/metabolismo
18.
Dev Cell ; 45(2): 183-197.e5, 2018 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-29689194

RESUMO

The adult mammalian intestine is composed of two connected structures, the absorptive villi and the crypts, which house progenitor cells. Mouse crypts develop postnatally and are the architectural unit of the stem cell niche, yet the pathways that drive their formation are not known. Here, we combine transcriptomic, quantitative morphometric, and genetic analyses to identify mechanisms of crypt development. We uncover the upregulation of a contractility gene network at the earliest stage of crypt formation, which drives myosin II-dependent apical constriction and invagination of the crypt progenitor cells. Subsequently, hinges form, compartmentalizing crypts from villi. Hinges contain basally constricted cells, and this cell shape change was inhibited by increased hemidesmosomal adhesion in Rac1 null mice. Loss of hinges resulted in reduced villar spacing, revealing an unexpected role for crypts in tissue architecture and physiology. These studies provide a framework for studying crypt morphogenesis and identify essential regulators of niche formation.


Assuntos
Compartimento Celular/fisiologia , Diferenciação Celular , Intestinos/citologia , Morfogênese/fisiologia , Neuropeptídeos/fisiologia , Nicho de Células-Tronco/fisiologia , Células-Tronco/citologia , Proteínas rac1 de Ligação ao GTP/fisiologia , Animais , Linhagem da Célula , Feminino , Integrinas/genética , Integrinas/metabolismo , Intestinos/fisiologia , Masculino , Camundongos , Camundongos Knockout , Miosina Tipo II/genética , Miosina Tipo II/metabolismo , Células-Tronco/fisiologia , Transcriptoma
19.
Elife ; 62017 09 04.
Artigo em Inglês | MEDLINE | ID: mdl-28869035

RESUMO

The physiological functions of microtubules (MTs) are poorly understood in many differentiated cell types. We developed a genetic toolkit to study MT dynamics and function in diverse cells. Using TRE-EB1-GFP mice, we found that MT dynamics are strongly suppressed in differentiated keratinocytes in two distinct steps due to alterations in both growth rate and lifetime. To understand the functions of these MT populations, we developed TRE-spastin mice to disrupt MTs in specific cell types. MT perturbation in post-mitotic keratinocytes had profound consequences on epidermal morphogenesis. We uncoupled cell-autonomous roles in cell flattening from non-cell-autonomous requirements for MTs in regulating proliferation, differentiation, and tissue architecture. This work uncovers physiological roles for MTs in epidermal development, and the tools described here will be broadly useful to study MT dynamics and functions in mammals.


Assuntos
Epiderme/crescimento & desenvolvimento , Microtúbulos/metabolismo , Animais , Diferenciação Celular , Regulação da Expressão Gênica , Genes Reporter , Proteínas de Fluorescência Verde/análise , Proteínas de Fluorescência Verde/genética , Camundongos , Proteínas Recombinantes de Fusão/análise , Proteínas Recombinantes de Fusão/genética , Coloração e Rotulagem
20.
Development ; 144(17): 3012-3021, 2017 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-28851722

RESUMO

Over the past several decades, numerous studies have greatly expanded our knowledge about how microtubule organization and dynamics are controlled in cultured cells in vitro However, our understanding of microtubule dynamics and functions in vivo, in differentiated cells and tissues, remains under-explored. Recent advances in generating genetic tools and imaging technologies to probe microtubules in situ, coupled with an increased interest in the functions of this cytoskeletal network in differentiated cells, are resulting in a renaissance. Here, we discuss the lessons learned from such approaches, which have revealed that, although some differentiated cells utilize conserved strategies to remodel microtubules, there is considerable diversity in the underlying molecular mechanisms of microtubule reorganization. This highlights a continued need to explore how differentiated cells regulate microtubule geometry in vivo.


Assuntos
Diferenciação Celular , Microtúbulos/metabolismo , Animais , Centrossomo/metabolismo , Humanos , Centro Organizador dos Microtúbulos/metabolismo , Modelos Biológicos
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