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1.
Biomed Pharmacother ; 138: 111521, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34311525

RESUMO

Euphorbiae pekinensis Radix (EP) is effective in treating various diseases, but it's toxicity is a major obstacle in use in clinical. Although EP was processed with vinegar to reduce it's toxicity, the detailed mechanism of toxicity in EP have not been clearly delineated. This study investigate the toxicity attenuation-mechanism of Euphorbiae pekinensis after being processed with vinegar (VEP) and the toxic mechanism of four compounds from EP on zebrafish embryos. The contents of four compounds decreased obviously in VEP. Correspondingly, slower development on embryos can be seen as some symptoms like reduction of heart rate, liver area and gastrointestinal peristalsis after exposed to the compounds. Some obvious pathological signals such as pericardial edema and yolk sac edema were observed. Furthermore, the compounds could increase the contents of MDA and GSH-PX and induce oxidative damage by inhibiting the activity of SOD. Also, four compounds could provoke apoptosis by up-regulating the expression level of p53, MDM2, Bax, Bcl-2 and activating the activity of caspase-3, caspase-9. In conclusion, the four compounds play an important role in the toxicity attenuation effects of VEP, which may be related to the apoptosis induction and oxidative damage. This would contribute to the clinical application and further toxicity-reduction mechanism research.


Assuntos
Euphorbia/toxicidade , Trato Gastrointestinal/efeitos dos fármacos , Coração/efeitos dos fármacos , Fígado/efeitos dos fármacos , Compostos Fitoquímicos/toxicidade , Extratos Vegetais/toxicidade , Peixe-Zebra/embriologia , Animais , Apoptose/efeitos dos fármacos , Proteínas Reguladoras de Apoptose/genética , Proteínas Reguladoras de Apoptose/metabolismo , Cardiotoxicidade , Embrião não Mamífero/efeitos dos fármacos , Embrião não Mamífero/metabolismo , Embrião não Mamífero/patologia , Euphorbia/química , Trato Gastrointestinal/embriologia , Trato Gastrointestinal/metabolismo , Coração/embriologia , Fígado/embriologia , Fígado/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Compostos Fitoquímicos/isolamento & purificação , Extratos Vegetais/isolamento & purificação , Proteínas de Peixe-Zebra/genética , Proteínas de Peixe-Zebra/metabolismo
2.
Commun Biol ; 4(1): 770, 2021 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-34162999

RESUMO

While the colonization of the embryonic gut by neural crest cells has been the subject of intense scrutiny over the past decades, we are only starting to grasp the morphogenetic transformations of the enteric nervous system happening in the fetal stage. Here, we show that enteric neural crest cell transit during fetal development from an isotropic cell network to a square grid comprised of circumferentially-oriented cell bodies and longitudinally-extending interganglionic fibers. We present ex-vivo dynamic time-lapse imaging of this isotropic-to-nematic phase transition and show that it occurs concomitantly with circular smooth muscle differentiation in all regions of the gastrointestinal tract. Using conditional mutant embryos with enteric neural crest cells depleted of ß1-integrins, we show that cell-extracellular matrix anchorage is necessary for ganglia to properly reorient. We demonstrate by whole mount second harmonic generation imaging that fibrous, circularly-spun collagen I fibers are in direct contact with neural crest cells during the orientation transition, providing an ideal orientation template. We conclude that smooth-muscle associated extracellular matrix drives a critical reorientation transition of the enteric nervous system in the mammalian fetus.


Assuntos
Trato Gastrointestinal/embriologia , Crista Neural/citologia , Animais , Adesão Celular , Diferenciação Celular , Matriz Extracelular/fisiologia , Trato Gastrointestinal/inervação , Integrina beta1/fisiologia , Camundongos , Músculo Liso/embriologia
3.
Am J Physiol Gastrointest Liver Physiol ; 319(4): G519-G528, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32877218

RESUMO

The first contractile waves in the developing embryonic gut are purely myogenic; they only involve smooth muscle. Here, we provide evidence for a transition from smooth muscle to interstitial cell of Cajal (ICC)-driven contractile waves in the developing chicken gut. In situ hybridization staining for anoctamin-1 (ANO1), a known ICC marker, shows that ICCs are already present throughout the gut, as from embryonic day (E)7. We devised a protocol to reveal ICC oscillatory and propagative calcium activity in embryonic gut whole mount and found that the first steady calcium oscillations in ICCs occur on (E14). We show that the activation of ICCs leads to an increase in contractile wave frequency, regularity, directionality, and velocity between E12 and E14. We finally demonstrate that application of the c-KIT antagonist imatinib mesylate in organ culture specifically depletes the ICC network and inhibits the transition to a regular rhythmic wave pattern. We compare our findings to existing results in the mouse and predict that a similar transition should take place in the human fetus between 12 and 14 wk of development. Together, our results point to an abrupt physiological transition from smooth muscle mesenchyme self-initiating waves to ICC-driven motility in the fetus and clarify the contribution of ICCs to the contractile wave pattern.NEW & NOTEWORTHY We reveal a sharp transition from smooth muscle to interstitial cell of Cajal (ICC)-driven motility in the chicken embryo, leading to higher-frequency, more rhythmic contractile waves. We predict the transition to happen between 12 and 14 embryonic wk in humans. We image for the first time the onset of ICC activity in an embryonic gut by calcium imaging. We show the first KIT and anoctamin-1 (ANO1) in situ hybridization micrographs in the embryonic chicken gut.


Assuntos
Motilidade Gastrointestinal/fisiologia , Células Intersticiais de Cajal/fisiologia , Intestinos/embriologia , Animais , Anoctamina-1/análise , Cálcio/metabolismo , Embrião de Galinha , Trato Gastrointestinal/embriologia , Trato Gastrointestinal/fisiologia , Humanos , Células Intersticiais de Cajal/química , Intestinos/fisiologia , Camundongos , Contração Muscular/fisiologia , Músculo Liso/embriologia , Músculo Liso/fisiologia , Fatores de Tempo
4.
J Neurosci ; 40(35): 6691-6708, 2020 08 26.
Artigo em Inglês | MEDLINE | ID: mdl-32690615

RESUMO

Precise extrinsic afferent (visceral sensory) and efferent (sympathetic and parasympathetic) innervation of the gut is fundamental for gut-brain cross talk. Owing to the limitation of intrinsic markers to distinctively visualize the three classes of extrinsic axons, which intimately associate within the gut mesentery, detailed information on the development of extrinsic gut-innervating axons remains relatively sparse. Here, we mapped extrinsic innervation of the gut and explored the relationships among various types of extrinsic axons during embryonic development in mice. Visualization with characterized intrinsic markers revealed that visceral sensory, sympathetic, and parasympathetic axons arise from different anatomic locations, project in close association via the gut mesentery, and form distinctive innervation patterns within the gut from embryonic day (E)10.5 to E16.5. Genetic ablation of visceral sensory trajectories results in the erratic extension of both sympathetic and parasympathetic axons, implicating that afferent axons provide an axonal scaffold to route efferent axons. Coculture assay further confirmed the attractive effect of sensory axons on sympathetic axons. Taken together, our study provides key information regarding the development of extrinsic gut-innervating axons occurring through heterotypic axonal interactions and provides an anatomic basis to uncover neural circuit assembly in the gut-brain axis (GBA).SIGNIFICANCE STATEMENT Understanding the development of extrinsic innervation of the gut is essential to unravel the bidirectional neural communication between the brain and the gut. Here, with characterized intrinsic markers targeting vagal sensory, spinal sensory, sympathetic, and parasympathetic axons, respectively, we comprehensively traced the spatiotemporal development of extrinsic axons to the gut during embryonic development in mice. Moreover, in line with the somatic nervous system, pretarget sorting via heterotypic axonal interactions is revealed to play critical roles in patterning extrinsic efferent trajectories to the gut. These findings provide basic anatomic information to explore the mechanisms underlying the process of assembling neural circuitry in the gut-brain axis (GBA).


Assuntos
Sistema Nervoso Autônomo/embriologia , Trato Gastrointestinal/inervação , Animais , Sistema Nervoso Autônomo/fisiologia , Axônios/fisiologia , Encéfalo/embriologia , Encéfalo/fisiologia , Trato Gastrointestinal/embriologia , Mesentério/embriologia , Mesentério/inervação , Camundongos , Morfogênese , Técnicas de Rastreamento Neuroanatômico
5.
Toxins (Basel) ; 12(6)2020 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-32521650

RESUMO

Harmful algal blooms (HAB) have become a major health concern worldwide, not just to humans that consume and recreate on contaminated waters, but also to the fauna that inhabit the environments surrounding affected areas. HABs contain heterotrophic bacteria, cyanobacterial lipopolysaccharide, and cyanobacterial toxins such as microcystins, that can cause severe toxicity in many aquatic species as well as bioaccumulation within various organs. Thus, the possibility of trophic transference of this toxin through the food chain has potentially important health implications for other organisms in the related food web. While some species have developed adaptions to attenuate the toxic effects of HAB toxins, there are still numerous species that remain vulnerable, including Lithobates catesbeiana (American bullfrog) tadpoles. In the current study we demonstrate that acute, short-term exposure of tadpoles to HAB toxins containing 1 µg/L (1 nmol/L) of total microcystins for only 7 days results in significant liver and intestinal toxicity within tadpoles. Exposed tadpoles had increased intestinal diameter, decreased intestinal fold heights, and a constant number of intestinal folds, indicating pathological intestinal distension, similar to what is seen in various disease processes, such as toxic megacolon. HAB-toxin-exposed tadpoles also demonstrated hepatocyte hypertrophy with increased hepatocyte binucleation consistent with carcinogenic and oxidative processes within the liver. Both livers and intestines of HAB-toxin-exposed tadpoles demonstrated significant increases in protein carbonylation consistent with oxidative stress and damage. These findings demonstrate that short-term exposure to HAB toxins, including microcystins, can have significant adverse effects in amphibian populations. This acute, short-term toxicity highlights the need to evaluate the influence HAB toxins may have on other vulnerable species within the food web and how those may ultimately also impact human health.


Assuntos
Trato Gastrointestinal/efeitos dos fármacos , Proliferação Nociva de Algas , Fígado/efeitos dos fármacos , Microcistinas/toxicidade , Rana catesbeiana , Microbiologia da Água , Animais , Cadeia Alimentar , Trato Gastrointestinal/embriologia , Trato Gastrointestinal/metabolismo , Larva/efeitos dos fármacos , Fígado/embriologia , Fígado/metabolismo , Carbonilação Proteica/efeitos dos fármacos , Rana catesbeiana/embriologia , Fatores de Tempo , Testes de Toxicidade Aguda
6.
BMC Biol ; 18(1): 68, 2020 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-32546156

RESUMO

BACKGROUND: The homeobox genes Pdx and Cdx are widespread across the animal kingdom and part of the small ParaHox gene cluster. Gene expression patterns suggest ancient roles for Pdx and Cdx in patterning the through-gut of bilaterian animals although functional data are available for few lineages. To examine evolutionary conservation of Pdx and Cdx gene functions, we focus on amphioxus, small marine animals that occupy a pivotal position in chordate evolution and in which ParaHox gene clustering was first reported. RESULTS: Using transcription activator-like effector nucleases (TALENs), we engineer frameshift mutations in the Pdx and Cdx genes of the amphioxus Branchiostoma floridae and establish mutant lines. Homozygous Pdx mutants have a defect in amphioxus endoderm, manifest as loss of a midgut region expressing endogenous GFP. The anus fails to open in homozygous Cdx mutants, which also have defects in posterior body extension and epidermal tail fin development. Treatment with an inverse agonist of retinoic acid (RA) signalling partially rescues the axial and tail fin phenotypes indicating they are caused by increased RA signalling. Gene expression analyses and luciferase assays suggest that posterior RA levels are kept low in wild type animals by a likely direct transcriptional regulation of a Cyp26 gene by Cdx. Transcriptome analysis reveals extensive gene expression changes in mutants, with a disproportionate effect of Pdx and Cdx on gut-enriched genes and a colinear-like effect of Cdx on Hox genes. CONCLUSIONS: These data reveal that amphioxus Pdx and Cdx have roles in specifying middle and posterior cell fates in the endoderm of the gut, roles that likely date to the origin of Bilateria. This conclusion is consistent with these two ParaHox genes playing a role in the origin of the bilaterian through-gut with a distinct anus, morphological innovations that contributed to ecological change in the Cambrian. In addition, we find that amphioxus Cdx promotes body axis extension through a molecular mechanism conserved with vertebrates. The axial extension role for Cdx dates back at least to the origin of Chordata and may have facilitated the evolution of the post-anal tail and active locomotion in chordates.


Assuntos
Canal Anal/embriologia , Trato Gastrointestinal/embriologia , Proteínas de Homeodomínio/genética , Anfioxos/embriologia , Mutação , Cauda/embriologia , Fatores de Transcrição/genética , Animais , Embrião não Mamífero , Desenvolvimento Embrionário/genética , Genes Homeobox , Proteínas de Homeodomínio/metabolismo , Anfioxos/genética , Fatores de Transcrição/metabolismo
7.
Gene Expr Patterns ; 35: 119097, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-32007595

RESUMO

The poly(C)-binding protein (PCBP) family members belong to a subtype of RNA-binding proteins that are ubiquitously expressed with diverse functions. In mammals, PCBP family, also known as hnRNP E family, is composed of four proteins, namely PCBP1, PCBP2, PCBP3 and PCBP4. So far, no study has been documented on the physiological roles of each member in vertebrate development. Here we analysed the spatiotemporal expression patterns of zebrafish (Danio rerio) pcbp2 (identical to pcbp1 and pcbp2 in mammals), pcbp3 and pcbp4 at various stages of zebrafish embryonic development by whole-mount in situ hybridization. Our results revealed that all pcbp genes are maternally expressed, especially pcbp2, which is strongly expressed from the embryogenetic stage to larva. The expression patterns of PCBP members are similar to each other at the very early developmental stage sharing with common strong expression in the intestine, otic vesicle, retina and brain of zebrafish. Subsequently, the messenger RNAs of PCBP members are gradually constrained and highly expressed in intestines of the larvae. Collectively, our study figured out the expression pattern of each PCBP member in diverse organogenesis during embryo development, indicating that PCBP members may play predominant roles in the development of neural and digestive systems to maintain their normal physiological functions. Moreover, the similar expression patterns at the developmental stages and organ types among this family suggest that the aberrant expression of these genes would lead to the neural or intestinal diseases.


Assuntos
Regulação da Expressão Gênica no Desenvolvimento , Organogênese , Proteínas de Ligação a RNA/genética , Proteínas de Peixe-Zebra/genética , Animais , Encéfalo/embriologia , Encéfalo/metabolismo , Trato Gastrointestinal/embriologia , Trato Gastrointestinal/metabolismo , Proteínas de Ligação a RNA/metabolismo , Retina/embriologia , Retina/metabolismo , Peixe-Zebra , Proteínas de Peixe-Zebra/metabolismo
8.
Zygote ; 28(3): 208-216, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32077403

RESUMO

In the present study, the morphological development of the Brycon amazonicus digestive tract is described to provide basic knowledge for nutritional studies and, therefore, increase the survival of this species during larviculture. Samples were collected from hatching up to 25 days of age, measured, processed and observed under a stereomicroscope and light microscopy. Newly hatched larvae presented their digestive tract as a straight tube, dorsal to the yolk sac, lined with a single layer of undifferentiated cells. At 24 h post-hatching (hPH), the buccopharyngeal cavity was open, but the posterior region of the digestive tube remained closed. At 25 hPH, the digestive tube was completely open and could be divided into buccopharyngeal cavity, oesophagus and intestine. At 35 hPH, the intestine presented a dilatation in the proximal region, which had the function of storing food. Differentiation of the stomach started at 83 hPH, and mucous cells were observed in the epithelium. These cells are important in the production of mucus, whose function is to protect the organ against acidity, although the gastric glands began developing only from 171 hPH, when three stomach regions were observed: cardiac, fundic and pyloric. The gastric glands were observed in the cardiac region, indicating that this organ already had digestive functionality. From 243 hPH, the absorption and assimilation of nutrients were already possible but, only from 412 hPH, the digestive tract was completely developed and functional.


Assuntos
Caraciformes/crescimento & desenvolvimento , Trato Gastrointestinal/crescimento & desenvolvimento , Animais , Região Branquial/citologia , Região Branquial/embriologia , Região Branquial/crescimento & desenvolvimento , Caraciformes/anatomia & histologia , Caraciformes/embriologia , Embrião não Mamífero/citologia , Embrião não Mamífero/embriologia , Desenvolvimento Embrionário/fisiologia , Mucosa Gástrica/citologia , Mucosa Gástrica/embriologia , Mucosa Gástrica/crescimento & desenvolvimento , Trato Gastrointestinal/citologia , Trato Gastrointestinal/embriologia , Larva/citologia , Larva/crescimento & desenvolvimento , Mucosa Bucal/citologia , Mucosa Bucal/embriologia , Mucosa Bucal/crescimento & desenvolvimento , Fatores de Tempo
9.
Pediatr Res ; 87(5): 847-852, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31756731

RESUMO

BACKGROUND: Fetal swallowing of human amniotic fluid (hAF) containing trophic factors (TFs) promotes gastrointestinal tract (GIT) development. Preterm birth interrupts hAF swallowing, which may increase the risk of necrotizing enterocolitis (NEC). Postnatally, it is difficult to replicate fetal swallowing of hAF due to volume. We aimed to evaluate whether hAF lyophilization is feasible and its effect on hAF-borne TFs. METHODS: We collected hAF (n = 16) from uncomplicated pregnancies. hAF was divided into three groups: unprocessed control (C), concentration by microfiltration (F), and by dialysis and lyophilization (L). EGF, HGF, GM-CSF, and TGF-α were measured in each group by multiplex assay. Bioavailability of TFs was measured by proliferation and LPS-induced IL-8 production by intestinal epithelial cells FHs74. RESULTS: After dialysis/lyophilization, GM-CSF and TGF-α were preserved with partial loss of EGF and HGF. hAF increased cell proliferation and reduced LPS-induced IL-8 production compared to medium alone. Compared to control, dialysis/lyophilization and filtration of hAF increased FHs74 cell proliferation (p < 0.001) and decreased LPS-induced IL-8 production (p < 0.01). CONCLUSIONS: Lyophilization and filtration of hAF is feasible with partial loss of TFs but maintains and even improves bioavailability of TFs measured by proliferation and LPS-induced IL-8 production by FHs74.


Assuntos
Líquido Amniótico/metabolismo , Enterocolite Necrosante/metabolismo , Liofilização , Trato Gastrointestinal/embriologia , Líquido Amniótico/química , Proliferação de Células , Criopreservação , Deglutição , Feminino , Fator Estimulador de Colônias de Granulócitos e Macrófagos/metabolismo , Humanos , Inflamação , Interleucina-8/metabolismo , Gravidez , Fator de Crescimento Transformador alfa/metabolismo
10.
BMC Dev Biol ; 19(1): 25, 2019 12 30.
Artigo em Inglês | MEDLINE | ID: mdl-31884948

RESUMO

BACKGROUND: Rab proteins are GTPases responsible for intracellular vesicular trafficking regulation. Rab11 proteins, members of the Rab GTPase family, are known to regulate vesicular recycling during embryonic development. In zebrafish, there are 3 rab11 paralogues, known as rab11a, rab11ba and rab11bb, sharing high identity with each other. However, the expression analysis of rab11 is so far lacking. RESULTS: Here, by phylogeny analysis, we found the three rab11 genes are highly conserved especially for their GTPase domains. We examined the expression patterns of rab11a, rab11ba and rab11bb using RT-PCR and in situ hybridization. We found that all the three genes were highly enriched in the central nervous system, but in different areas of the brain. Apart from brain, rab11a was also expressed in caudal vein, pronephric duct, proctodeum, pharyngeal arches and digestive duct, rab11ba was detected to express in muscle, and rab11bb was expressed in kidney, fin and spinal cord. Different from rab11a and rab11ba, which both have maternal expressions in embryos, rab11bb only expresses during 24hpf to 96hpf. CONCLUSIONS: Our results suggest that rab11 genes play important but distinct roles in the development of the nervous system in zebrafish. The findings could provide new evidences for better understanding the functions of rab11 in the development of zebrafish embryos.


Assuntos
Peixe-Zebra/embriologia , Proteínas rab de Ligação ao GTP/genética , Proteínas rab de Ligação ao GTP/metabolismo , Animais , Sistema Nervoso Central/embriologia , Sistema Nervoso Central/metabolismo , Sequência Conservada , Feminino , Trato Gastrointestinal/embriologia , Trato Gastrointestinal/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Herança Materna , Família Multigênica , Domínios Proteicos , Distribuição Tecidual , Peixe-Zebra/genética , Peixe-Zebra/metabolismo , Proteínas de Peixe-Zebra/química , Proteínas de Peixe-Zebra/genética , Proteínas de Peixe-Zebra/metabolismo , Proteínas rab de Ligação ao GTP/química
11.
Autophagy ; 15(11): 2019-2021, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31470757

RESUMO

Macroautophagy/autophagy has been demonstrated to play an essential role in embryonic development. However, the role of autophagy during human fetal digestive tract development has not been investigated. Here, by using over 5,000 human embryonic digestive tract cells ranging from 6 weeks to 25 weeks, we explored the dynamic expression of autophagy-related genes at single-cell resolution, and found that the transcriptional activity of autophagy-related genes boosted remarkably and specifically in the early (between 6 and 9 weeks) stages. Interestingly, the small intestine cells at 9 weeks showed the most significant enrichment of autophagy-related genes than any other stages. In summary, our results for the first time revealed that autophagy may play an essential role in the development of the digestive tract, especially for the small intestine, in early human embryos. Abbreviations: GI: gastrointestinal; S-Intes: small intestine; t-SNE: t-distributed stochastic neighbor embedding.


Assuntos
Proteínas Relacionadas à Autofagia/genética , Autofagia/genética , Trato Gastrointestinal/embriologia , Trato Gastrointestinal/metabolismo , Proteínas Relacionadas à Autofagia/metabolismo , Bases de Dados Genéticas , Feto , Genômica , Humanos , Análise de Sequência de RNA , Análise de Célula Única
12.
Anat Sci Int ; 94(2): 192-198, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30600445

RESUMO

In this study we examined the ontogenic development of the digestive tract of Vimba bream (Vimba vimba, Family: Cyprinidae) during the first 60 days of life (hatching to 60 days after hatching [DAH]). Samples of developing Vimba bream were randomly selected at various stages of development: 1-8, 10, 15, 20, 25, 30, 40, 50, and 60 DAH. For the histological and histochemical studies on the development of the alimentary canal, tissue sections prepared from the sampled hatchlings were stained with hematoxylin-eosin and periodic acid-Schiff and observed under a light microscope. The histological structures of both the mouth and esophagus were fully developed at 5 and 7 DAH, respectively. Intestinal differentiation was observed at 2 DAH, while mucosal folds appeared on the intestinal bulb at 7 DAH. At 5 DAH, with the appearance of goblet cells in the epithelium of the mouth, pharynx, and esophagus, the larvae showed secretion activity in these organs. At 6 DAH, secretion was observed in the intestine; at this stage of development, the surface of the gastrointestinal tract was covered in a neutral mucous-like layer of polysaccharide. The histological observations indicate that the early development of the digestive tract in Vimba vimba enables larvae to efficiently ingest and digest exogenous feed very quickly after hatching.


Assuntos
Peixes/anatomia & histologia , Peixes/embriologia , Trato Gastrointestinal/anatomia & histologia , Trato Gastrointestinal/embriologia , Larva/anatomia & histologia , Larva/crescimento & desenvolvimento , Animais , Digestão , Ingestão de Alimentos , Peixes/crescimento & desenvolvimento , Peixes/fisiologia , Trato Gastrointestinal/crescimento & desenvolvimento , Trato Gastrointestinal/fisiologia , Larva/fisiologia , Polissacarídeos/metabolismo
13.
Nature ; 565(7740): 480-484, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30651642

RESUMO

The embryonic gut tube is a cylindrical structure from which the respiratory and gastrointestinal tracts develop1. Although the early emergence of the endoderm as an epithelial sheet2,3 and later morphogenesis of the definitive digestive and respiratory organs4-6 have been investigated, the intervening process of gut tube formation remains relatively understudied7,8. Here we investigate the molecular control of macroscopic forces underlying early morphogenesis of the gut tube in the chick embryo. The gut tube has been described as forming from two endodermal invaginations-the anterior intestinal portal (AIP) towards the rostral end of the embryo and the caudal intestinal portal (CIP) at the caudal end-that migrate towards one another, internalizing the endoderm until they meet at the yolk stalk (umbilicus in mammals)1,6. Migration of the AIP to form foregut has been descriptively characterized8,9, but the hindgut is likely to form by a distinct mechanism that has not been fully explained10. We find that the hindgut is formed by collective cell movements through a stationary CIP, rather than by movement of the CIP itself. Further, combining in vivo imaging, biophysics and mathematical modelling with molecular and embryological approaches, we identify a contractile force gradient that drives cell movements in the hindgut-forming endoderm, enabling tissue-scale posterior extension of the forming hindgut tube. The force gradient, in turn, is established in response to a morphogenic gradient of fibroblast growth factor signalling. As a result, we propose that an important positive feedback arises, whereby contracting cells draw passive cells from low to high fibroblast growth factor levels, recruiting them to contract and pull more cells into the elongating hindgut. In addition to providing insight into the early gut development, these findings illustrate how large-scale tissue level forces can be traced to developmental signals during vertebrate morphogenesis.


Assuntos
Trato Gastrointestinal/embriologia , Morfogênese , Animais , Padronização Corporal , Movimento Celular , Embrião de Galinha , Endoderma/citologia , Endoderma/embriologia , Endoderma/metabolismo , Fator 8 de Crescimento de Fibroblasto/metabolismo , Trato Gastrointestinal/citologia , Trato Gastrointestinal/metabolismo , Transdução de Sinais
14.
Genetics ; 210(2): 357-396, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30287514

RESUMO

The gastrointestinal tract has recently come to the forefront of multiple research fields. It is now recognized as a major source of signals modulating food intake, insulin secretion and energy balance. It is also a key player in immunity and, through its interaction with microbiota, can shape our physiology and behavior in complex and sometimes unexpected ways. The insect intestine had remained, by comparison, relatively unexplored until the identification of adult somatic stem cells in the Drosophila intestine over a decade ago. Since then, a growing scientific community has exploited the genetic amenability of this insect organ in powerful and creative ways. By doing so, we have shed light on a broad range of biological questions revolving around stem cells and their niches, interorgan signaling and immunity. Despite their relatively recent discovery, some of the mechanisms active in the intestine of flies have already been shown to be more widely applicable to other gastrointestinal systems, and may therefore become relevant in the context of human pathologies such as gastrointestinal cancers, aging, or obesity. This review summarizes our current knowledge of both the formation and function of the Drosophila melanogaster digestive tract, with a major focus on its main digestive/absorptive portion: the strikingly adaptable adult midgut.


Assuntos
Drosophila melanogaster/fisiologia , Trato Gastrointestinal/fisiologia , Animais , Drosophila melanogaster/anatomia & histologia , Drosophila melanogaster/embriologia , Trato Gastrointestinal/anatomia & histologia , Trato Gastrointestinal/embriologia , Morfogênese
15.
J Cell Biol ; 217(9): 2987-3005, 2018 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-30061107

RESUMO

The emerging field of transcriptional regulation of cell shape changes aims to address the critical question of how gene expression programs produce a change in cell shape. Together with cell growth, division, and death, changes in cell shape are essential for organ morphogenesis. Whereas most studies of cell shape focus on posttranslational events involved in protein organization and distribution, cell shape changes can be genetically programmed. This review highlights the essential role of transcriptional regulation of cell shape during morphogenesis of the heart, lungs, gastrointestinal tract, and kidneys. We emphasize the evolutionary conservation of these processes across different model organisms and discuss perspectives on open questions and research avenues that may provide mechanistic insights toward understanding birth defects.


Assuntos
Forma Celular/fisiologia , Trato Gastrointestinal/embriologia , Coração/embriologia , Rim/embriologia , Pulmão/embriologia , Organogênese/fisiologia , Animais , Anormalidades Congênitas/embriologia , Regulação da Expressão Gênica no Desenvolvimento , Humanos , Transcrição Genética/genética
16.
Nat Rev Neurosci ; 19(9): 552-565, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30046054

RESUMO

The gastrointestinal tract contains its own set of intrinsic neuroglial circuits - the enteric nervous system (ENS) - which detects and responds to diverse signals from the environment. Here, we address recent advances in the understanding of ENS development, including how neural-crest-derived progenitors migrate into and colonize the bowel, the formation of ganglionated plexuses and the molecular mechanisms of enteric neuronal and glial diversification. Modern lineage tracing and transcription-profiling technologies have produced observations that simultaneously challenge and affirm long-held beliefs about ENS development. We review many genetic and environmental factors that can alter ENS development and exert long-lasting effects on gastrointestinal function, and discuss how developmental defects in the ENS might account for some of the large burden of digestive disease.


Assuntos
Sistema Nervoso Entérico/embriologia , Trato Gastrointestinal/embriologia , Neurônios/fisiologia , Animais , Diferenciação Celular , Trato Gastrointestinal/inervação , Humanos , Crista Neural/embriologia , Neurogênese
17.
Nat Neurosci ; 21(8): 1061-1071, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29988069

RESUMO

Early prenatal stress disrupts maternal-to-offspring microbiota transmission and has lasting effects on metabolism, physiology, cognition, and behavior in male mice. Here we show that transplantation of maternal vaginal microbiota from stressed dams into naive pups delivered by cesarean section had effects that partly resembled those seen in prenatally stressed males. However, transplantation of control maternal vaginal microbiota into prenatally stressed pups delivered by cesarean section did not rescue the prenatal-stress phenotype. Prenatal stress was associated with alterations in the fetal intestinal transcriptome and niche, as well as with changes in the adult gut that were altered by additional stress exposure in adulthood. Further, maternal vaginal transfer also partially mediated the effects of prenatal stress on hypothalamic gene expression, as observed after chronic stress in adulthood. These findings suggest that the maternal vaginal microbiota contribute to the lasting effects of prenatal stress on gut and hypothalamus in male mice.


Assuntos
Trato Gastrointestinal/fisiologia , Hipotálamo/fisiologia , Microbiota , Efeitos Tardios da Exposição Pré-Natal , Estresse Psicológico/fisiopatologia , Vagina/microbiologia , Animais , Peso Corporal , Cesárea , Feminino , Trato Gastrointestinal/embriologia , Expressão Gênica/genética , Sistema Hipotálamo-Hipofisário , Hipotálamo/metabolismo , Absorção Intestinal , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Núcleo Hipotalâmico Paraventricular/metabolismo , Fenótipo , Gravidez , Transcriptoma
18.
Dev Biol ; 441(2): 285-296, 2018 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-29883660

RESUMO

Through the course of evolution, the gastrointestinal (GI) tract has been modified to maximize nutrient absorption, forming specialized segments that are morphologically and functionally distinct. Here we show that the GI tract of the Mexican tetra, Astyanax mexicanus, has distinct regions, exhibiting differences in morphology, motility, and absorption. We found that A. mexicanus populations adapted for life in subterranean caves exhibit differences in the GI segments compared to those adapted to surface rivers. Cave-adapted fish exhibit bi-directional churning motility in the stomach region that is largely absent in river-adapted fish. We investigated how this motility pattern influences intestinal transit of powdered food and live prey. We found that powdered food is more readily emptied from the cavefish GI tract. In contrast, the transit of live rotifers from the stomach region to the midgut occurs more slowly in cavefish compared to surface fish, consistent with the presence of churning motility. Differences in intestinal motility and transit likely reflect adaptation to unique food sources available to post-larval A. mexicanus in the cave and river environments. We found that cavefish grow more quickly than surface fish when fed ad libitum, suggesting that altered GI function may aid in nutrient consumption or absorption. We did not observe differences in enteric neuron density or smooth muscle organization between cavefish and surface fish. Altered intestinal motility in cavefish could instead be due to changes in the activity or patterning of the enteric nervous system. Exploring this avenue will lead to a better understanding of how the GI tract evolves to maximize energy assimilation from novel food sources.


Assuntos
Caraciformes/embriologia , Comportamento Alimentar/fisiologia , Motilidade Gastrointestinal/fisiologia , Trato Gastrointestinal/embriologia , Morfogênese/fisiologia , Animais , Sistema Nervoso Entérico/embriologia , Trato Gastrointestinal/inervação , Músculo Liso/embriologia
19.
Nat Cell Biol ; 20(6): 721-734, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29802404

RESUMO

The development of the digestive tract is critical for proper food digestion and nutrient absorption. Here, we analyse the main organs of the digestive tract, including the oesophagus, stomach, small intestine and large intestine, from human embryos between 6 and 25 weeks of gestation as well as the large intestine from adults using single-cell RNA-seq analyses. In total, 5,227 individual cells are analysed and 40 cell types clearly identified. Their crucial biological features, including developmental processes, signalling pathways, cell cycle, nutrient digestion and absorption metabolism, and transcription factor networks, are systematically revealed. Moreover, the differentiation and maturation processes of the large intestine are thoroughly investigated by comparing the corresponding transcriptome profiles between embryonic and adult stages. Our work offers a rich resource for investigating the gene regulation networks of the human fetal digestive tract and adult large intestine at single-cell resolution.


Assuntos
Células Epiteliais/fisiologia , Trato Gastrointestinal/fisiologia , Perfilação da Expressão Gênica/métodos , Regulação da Expressão Gênica no Desenvolvimento , Análise de Sequência de RNA/métodos , Análise de Célula Única/métodos , Transcriptoma , Adulto , Fatores Etários , Diferenciação Celular/genética , Proliferação de Células/genética , Células Epiteliais/metabolismo , Trato Gastrointestinal/embriologia , Trato Gastrointestinal/metabolismo , Marcadores Genéticos , Genótipo , Idade Gestacional , Humanos , Morfogênese , Fenótipo , Fatores de Tempo
20.
Sci Rep ; 8(1): 5995, 2018 04 16.
Artigo em Inglês | MEDLINE | ID: mdl-29662083

RESUMO

During embryonic development, most organs are in a state of mechanical compression because they grow in a confined and limited amount of space within the embryo's body; the early gut is an exception because it physiologically herniates out of the coelom. We demonstrate here that physiological hernia is caused by a tensile force transmitted by the vitelline duct on the early gut loop at its attachment point at the umbilicus. We quantify this tensile force and show that applying tension for 48 h induces stress-dependent elongational growth of the embryonic gut in culture, with an average 90% length increase (max: 200%), 65% volume increase (max: 160%), 50% dry mass increase (max: 100%), and 165% cell number increase (max: 300%); this mechanical cue is required for organ growth as guts not subject to tension do not grow. We demonstrate that growth results from increased cell proliferation when tension is applied. These results outline the essential role played by mechanical forces in shaping and driving the proliferation of embryonic organs.


Assuntos
Trato Gastrointestinal/embriologia , Estresse Mecânico , Animais , Fenômenos Biomecânicos , Proliferação de Células , Embrião de Galinha , Motilidade Gastrointestinal , Trato Gastrointestinal/anatomia & histologia , Trato Gastrointestinal/citologia , Trato Gastrointestinal/fisiologia , Técnicas de Cultura de Órgãos , Tamanho do Órgão , Resistência à Tração
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