RESUMEN
Yolk sac (YS) CSF1 receptor positive (CSF1R+) cells are thought to be the progenitors for tissue-resident macrophages present in various tissues. The YS progenitors for tissue-resident macrophages are referred to as erythroid-myeloid progenitors (EMPs). However, diverse types of hematopoietic progenitors are present in the early YS, thus it is not precisely known which type of hematopoietic cell gives rise to the CSF1R+ lineage. In this study, an analysis was conducted to determine when CSF1R+ progenitors appeared in the early YS. It showed that CSF1R+ cells appeared in the YS as early as embryonic day 9 (E9) and that the earliest hematopoietic progenitors that differentiate into CSF1R+ cells were found in E8. Since these progenitors possessed the capability to generate primitive erythroid cells, it was likely that primitive erythroid lineages shared progenitors with the CSF1R+ lineage. Mutual antagonism appears to work between PU.1 and GATA1 when CSF1R+ cells appear in the early YS. One day later (E9), multiple progenitors, including myeloid-restricted progenitors and multipotent progenitors, in the YS could immediately generate CSF1R+ cells. These results suggest that EMPs are not an exclusive source for the CSF1R+ lineage; rather, multiple hematopoietic cell populations give rise to CSF1R+ lineage in the early YS.
Asunto(s)
Hematopoyesis , Células Madre Hematopoyéticas/fisiología , Macrófagos , Saco Vitelino/inmunología , Animales , Diferenciación Celular , Linaje de la Célula , Desarrollo Embrionario , Femenino , Ratones , Saco Vitelino/crecimiento & desarrollo , Saco Vitelino/fisiologíaRESUMEN
Yolk sac (YS) hematopoiesis is critical for the survival of the embryo and a major source of tissue-resident macrophages that persist into adulthood. Yet, the transcriptional and epigenetic regulation of YS hematopoiesis remains poorly characterized. Here we report that the epigenetic regulator Ezh2 is essential for YS hematopoiesis but dispensable for subsequent aorta-gonad-mesonephros (AGM) blood development. Loss of EZH2 activity in hemogenic endothelium (HE) leads to the generation of phenotypically intact but functionally deficient erythro-myeloid progenitors (EMPs), while the generation of primitive erythroid cells is not affected. EZH2 activity is critical for the generation of functional EMPs at the onset of the endothelial-to-hematopoietic transition but subsequently dispensable. We identify a lack of Wnt signaling downregulation as the primary reason for the production of non-functional EMPs. Together, our findings demonstrate a critical and stage-specific role of Ezh2 in modulating Wnt signaling during the generation of EMPs from YS HE.
Asunto(s)
Proteína Potenciadora del Homólogo Zeste 2/genética , Células Eritroides/metabolismo , Regulación del Desarrollo de la Expresión Génica , Células Madre Embrionarias de Ratones/metabolismo , Células Progenitoras Mieloides/metabolismo , Proteínas de Transporte Vesicular/genética , Saco Vitelino/metabolismo , Animales , Diferenciación Celular , Embrión de Mamíferos , Proteína Potenciadora del Homólogo Zeste 2/deficiencia , Epigénesis Genética , Células Eritroides/citología , Femenino , Feto , Genes Reporteros , Hematopoyesis/genética , Hígado/citología , Hígado/crecimiento & desarrollo , Hígado/metabolismo , Proteínas Luminiscentes/genética , Proteínas Luminiscentes/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Células Madre Embrionarias de Ratones/citología , Células Progenitoras Mieloides/patología , Cultivo Primario de Células , Proteínas de Transporte Vesicular/metabolismo , Vía de Señalización Wnt , Saco Vitelino/citología , Saco Vitelino/crecimiento & desarrollo , Proteína Fluorescente RojaRESUMEN
Human embryogenesis entails complex signalling interactions between embryonic and extra-embryonic cells. However, how extra-embryonic cells direct morphogenesis within the human embryo remains largely unknown due to a lack of relevant stem cell models. Here, we have established conditions to differentiate human pluripotent stem cells (hPSCs) into yolk sac-like cells (YSLCs) that resemble the post-implantation human hypoblast molecularly and functionally. YSLCs induce the expression of pluripotency and anterior ectoderm markers in human embryonic stem cells (hESCs) at the expense of mesoderm and endoderm markers. This activity is mediated by the release of BMP and WNT signalling pathway inhibitors, and, therefore, resembles the functioning of the anterior visceral endoderm signalling centre of the mouse embryo, which establishes the anterior-posterior axis. Our results implicate the yolk sac in epiblast cell fate specification in the human embryo and propose YSLCs as a tool for studying post-implantation human embryo development in vitro.
Asunto(s)
Estratos Germinativos/crecimiento & desarrollo , Células Madre Pluripotentes/metabolismo , Saco Vitelino/crecimiento & desarrollo , Animales , Línea Celular , Ectodermo/crecimiento & desarrollo , Desarrollo Embrionario , Humanos , RatonesRESUMEN
The extra-embryonic hypoblast/visceral endoderm of Placentalia carries out a variety of functions during gestation, including hematopoietic induction. Results of decades-old and recent experiments have provided compelling evidence that, in addition to its inducing properties, hypoblast/visceral endoderm itself is a source of placental blood cells. Those observations that highlight extra-embryonic endoderm's role as an overlooked source of placental blood cells across species are briefly discussed here, with suggestions for future exploration.
Asunto(s)
Alantoides/citología , Células Sanguíneas/citología , Endodermo/citología , Eritroblastos/citología , Placenta/citología , Saco Vitelino/citología , Alantoides/crecimiento & desarrollo , Alantoides/metabolismo , Animales , Células Sanguíneas/metabolismo , Proteínas Cromosómicas no Histona/genética , Proteínas Cromosómicas no Histona/metabolismo , Endodermo/crecimiento & desarrollo , Endodermo/metabolismo , Eritroblastos/metabolismo , Femenino , Proteínas Fetales/genética , Proteínas Fetales/metabolismo , Regulación del Desarrollo de la Expresión Génica , Ratones , Factor 3 de Transcripción de Unión a Octámeros/genética , Factor 3 de Transcripción de Unión a Octámeros/metabolismo , Receptor Patched-1/genética , Receptor Patched-1/metabolismo , Placenta/metabolismo , Embarazo , Proteínas de Dominio T Box/genética , Proteínas de Dominio T Box/metabolismo , Saco Vitelino/crecimiento & desarrollo , Saco Vitelino/metabolismoRESUMEN
AIM: The yolk sac (YS) has been reported as a reliable predictor of adverse pregnancy outcomes, however, it has always been evaluated cross-sectionally with a single ultrasound per patient. We sought to validate the use of YS dimensions in serial ultrasounds throughout the first 10 weeks of singleton and multiple gestations. METHODS: This was a prospective cohort study where YS diameters were serially obtained with 2D ultrasound in singleton and multiple gestations from 5 to 11 weeks. Nonparametric test were used for comparisons with P < 0.05 indicating significance. RESULTS: One hundred ninety-three patients were included, 42 twins (3 monochorionic and 39 dichorionic), 2 triplets (monochorionic twins plus a singleton) and 148 singleton pregnancies (238 total fetuses). There was no difference in YS dimensions in singleton versus multiple pregnancies. Starting at 5 weeks' gestation, the YS increased 0.4 mm (95% CI 0.3-0.5 mm) per week until 10 weeks' gestation. Forty-five fetuses were lost in the first trimester. The risk of pregnancy loss was higher with a large YS until 8 weeks (P ≤ 0.001), while after 8 weeks it was higher with a small YS (P < 0.005). CONCLUSION: We established a nomogram of YS development during the first 10 weeks of pregnancy. The YS reliably detected pregnancies that ended in loss as early as 6 weeks' gestation. The YS was either smaller or larger than in ongoing pregnancies. While all pregnancies with large YS were lost within 10 weeks, those with smaller YS were lost beyond the first 10 weeks.
Asunto(s)
Primer Trimestre del Embarazo/fisiología , Saco Vitelino/crecimiento & desarrollo , Adulto , Femenino , Humanos , Nomogramas , Proyectos Piloto , Embarazo , Estudios Prospectivos , Valores de Referencia , Ultrasonografía , Saco Vitelino/diagnóstico por imagenRESUMEN
It is well established that haematopoietic stem and progenitor cells (HSPCs) are generated from a transient subset of specialized endothelial cells termed haemogenic, present in the yolk sac, placenta and aorta, through an endothelial-to-haematopoietic transition (EHT). HSPC generation via EHT is thought to be restricted to the early stages of development. By using experimental embryology and genetic approaches in birds and mice, respectively, we document here the discovery of a bone marrow haemogenic endothelium in the late fetus/young adult. These cells are capable of de novo producing a cohort of HSPCs in situ that harbour a very specific molecular signature close to that of aortic endothelial cells undergoing EHT or their immediate progenies, i.e., recently emerged HSPCs. Taken together, our results reveal that HSPCs can be generated de novo past embryonic stages. Understanding the molecular events controlling this production will be critical for devising innovative therapies.
Asunto(s)
Células de la Médula Ósea/metabolismo , Linaje de la Célula/genética , Regulación del Desarrollo de la Expresión Génica , Hemangioblastos/metabolismo , Células Madre Hematopoyéticas/metabolismo , Animales , Animales Modificados Genéticamente , Aorta/citología , Aorta/metabolismo , Células de la Médula Ósea/citología , Diferenciación Celular , Pollos , Embrión de Mamíferos , Embrión no Mamífero , Femenino , Feto , Perfilación de la Expresión Génica , Redes Reguladoras de Genes , Hemangioblastos/citología , Trasplante de Células Madre Hematopoyéticas , Células Madre Hematopoyéticas/citología , Heterocigoto , Homocigoto , Masculino , Ratones , Embarazo , Saco Vitelino/citología , Saco Vitelino/crecimiento & desarrollo , Saco Vitelino/metabolismoRESUMEN
Cell-cell junctions respond to mechanical forces by changing their organization and function. To gain insight into the mechanochemical basis underlying junction mechanosensitivity, we analyzed tight junction (TJ) formation between the enveloping cell layer (EVL) and the yolk syncytial layer (YSL) in the gastrulating zebrafish embryo. We found that the accumulation of Zonula Occludens-1 (ZO-1) at TJs closely scales with tension of the adjacent actomyosin network, revealing that these junctions are mechanosensitive. Actomyosin tension triggers ZO-1 junctional accumulation by driving retrograde actomyosin flow within the YSL, which transports non-junctional ZO-1 clusters toward the TJ. Non-junctional ZO-1 clusters form by phase separation, and direct actin binding of ZO-1 is required for stable incorporation of retrogradely flowing ZO-1 clusters into TJs. If the formation and/or junctional incorporation of ZO-1 clusters is impaired, then TJs lose their mechanosensitivity, and consequently, EVL-YSL movement is delayed. Thus, phase separation and flow of non-junctional ZO-1 confer mechanosensitivity to TJs.
Asunto(s)
Desarrollo Embrionario/genética , Mecanotransducción Celular/genética , Uniones Estrechas/genética , Proteína de la Zonula Occludens-1/genética , Citoesqueleto de Actina/genética , Actomiosina/genética , Animales , Animales Modificados Genéticamente/genética , Animales Modificados Genéticamente/crecimiento & desarrollo , Embrión no Mamífero/fisiología , Regulación del Desarrollo de la Expresión Génica/genética , Humanos , Proteínas de la Membrana/genética , Ratones , Fosfoproteínas/genética , Unión Proteica , Uniones Estrechas/fisiología , Saco Vitelino/crecimiento & desarrollo , Saco Vitelino/metabolismo , Pez Cebra/genética , Pez Cebra/crecimiento & desarrolloRESUMEN
The yolk sac is the first site of blood-cell production during embryonic development in both murine and human. Heat shock proteins (HSPs), including HSP70 and HSP27, have been shown to play regulatory roles during erythropoiesis. However, it remains unknown whether HSP60, a molecular chaperone that resides mainly in mitochondria, could also regulate early erythropoiesis. In this study, we used Tie2-Cre to deactivate the Hspd1 gene in both hematopoietic and vascular endothelial cells, and found that Tie2-Cre+Hspd1f/f (HSP60CKO) mice were embryonic lethal between the embryonic day 10.5 (E10.5) and E11.5, exhibiting growth retardation, anemia, and vascular defects. Of these, anemia was observed first, independently of vascular and growth phenotypes. Reduced numbers of erythrocytes, as well as an increase in cell apoptosis, were found in the HSP60CKO yolk sac as early as E9.0, indicating that deletion of HSP60 led to abnormality in yolk sac erythropoiesis. Deletion of HSP60 was also able to reduce mitochondrial membrane potential and the expression of the voltage-dependent anion channel (VDAC) in yolk sac erythrocytes. Furthermore, cyclosporine A (CsA), which is a well-recognized modulator in regulating the opening of the mitochondrial permeability transition pore (mPTP) by interacting with Cyclophilin D (CypD), could significantly decrease cell apoptosis and partially restore VDAC expression in mutant yolk sac erythrocytes. Taken together, we demonstrated an essential role of HSP60 in regulating yolk sac cell survival partially via a mPTP-dependent mechanism.
Asunto(s)
Chaperonina 60/metabolismo , Desarrollo Embrionario/genética , Eritropoyesis/genética , Proteínas Mitocondriales/metabolismo , Saco Vitelino/citología , Anemia/genética , Animales , Apoptosis/efectos de los fármacos , Apoptosis/genética , Chaperonina 60/genética , Ciclosporina/farmacología , Embrión de Mamíferos/metabolismo , Embrión de Mamíferos/fisiopatología , Células Endoteliales/metabolismo , Eritrocitos/metabolismo , Eritropoyesis/fisiología , Femenino , Regulación del Desarrollo de la Expresión Génica/genética , Células Madre Hematopoyéticas/metabolismo , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Potencial de la Membrana Mitocondrial/genética , Ratones , Proteínas Mitocondriales/genética , Embarazo , Canales Aniónicos Dependientes del Voltaje/efectos de los fármacos , Canales Aniónicos Dependientes del Voltaje/metabolismo , Saco Vitelino/crecimiento & desarrollo , Saco Vitelino/metabolismo , Saco Vitelino/patologíaRESUMEN
The chicken yolk sac (YS) plays an important role in nutrient absorption and immune function for the developing embryo. The avian ß-defensins (AvBD) are cationic peptides that are important members of the innate immune system. The objective of this study was to profile AvBD mRNA expression patterns and distribution of cells expressing AvBD mRNA in the chicken YS. Expression of AvBD1, 2, 7, and 10 mRNA was low at embryonic day 7 (e7), increased to e9 through e13 and then declined to e19. Using in situ hybridization, AvBD10 mRNA was found to be expressed in endodermal epithelial cells, while AvBD1, 2, and 7 mRNA were expressed in heterophils. The developmental expression pattern and distribution of AvBD mRNA in the YS reveals the importance of these genes to protection of the developing chick embryo.
Asunto(s)
Proteínas Aviares/genética , Desarrollo Embrionario/inmunología , Regulación del Desarrollo de la Expresión Génica/inmunología , Saco Vitelino/inmunología , beta-Defensinas/genética , Animales , Proteínas Aviares/inmunología , Embrión de Pollo , Pollos , Endodermo/citología , Endodermo/inmunología , Endodermo/metabolismo , Células Epiteliales/inmunología , Células Epiteliales/metabolismo , ARN Mensajero/metabolismo , Saco Vitelino/crecimiento & desarrollo , Saco Vitelino/metabolismo , beta-Defensinas/inmunologíaRESUMEN
Macrophages serve multiple functions including immune regulation, morphogenesis, tissue homeostasis and healing reactions. The current paradigm holds that mammary gland macrophages first arise postnatally during the prepubertal period from the bone marrow-derived monocytes. Here we delineate the origins of tissue-resident mammary gland macrophages using high-dimension phenotypic analyses, cell-fate mapping experiments, gene-deficient mice lacking selective macrophage subtypes, and antibody-based depletion strategies. We show that tissue-resident macrophages are found in mammary glands already before birth, and that the yolk sac-derived and fetal liver-derived macrophages outnumber the adult-derived macrophages in the mammary gland also in the adulthood. In addition, fetal-derived mammary gland macrophages have a characteristic phenotype, display preferential periductal and perivascular localization, and are highly active in scavenging. These findings identify fetal-derived macrophages as the predominant leukocyte type in the adult mammary gland stroma, and reveal previously unknown complexity of macrophage biology in the breast.
Asunto(s)
Linaje de la Célula/fisiología , Macrófagos/fisiología , Glándulas Mamarias Animales/citología , Monocitos/fisiología , Morfogénesis/fisiología , Animales , Diferenciación Celular , Femenino , Feto/citología , Hígado/citología , Hígado/crecimiento & desarrollo , Masculino , Ratones , Ratones Transgénicos , Modelos Animales , Saco Vitelino/citología , Saco Vitelino/crecimiento & desarrolloRESUMEN
INTRODUCTION: The human yolk sac provides the embryo with stem cells, nutrients, and gas exchange. We hypothesized that more maternal resources, reflected in body size and body composition, would condition a a larger yolk sac, ensuring resources for the growing embryo. Thus, we aimed to determine the relation between maternal size in early pregnancy and yolk sac size. MATERIAL AND METHODS: This subsidiary study was embedded in the multinational World Health Organization fetal growth project that included healthy women with a body mass index of 18-30, reliable information of their regular last menstrual period and singleton pregnancies. Yolk sac diameter, crown-rump length, and maternal height, weight, body mass index, and body composition were assessed before 13 weeks of gestation, and the fetal biometry was repeated during the pregnancy. RESULTS: Of 140 participants, 122 with a successful yolk sac measurement were entered in the present analysis. Maternal weight was negatively associated with the yolk sac diameter (P = 0.007) and so was maternal height (P = 0.011), fat mass (P = 0.037), and lean body mass (P = 0.018), but not body mass index (P = 0.121). Significant effects were predominantly due to the female embryos and could be traced at 24 weeks of gestation. That is, a small yolk sac : crown-rump length ratio in early pregnancy was associated with a high fetal abdominal circumference (P < 0.001) and estimated fetal weight (P = 0.001). CONCLUSIONS: The human yolk sac is involved in the regulation of embryonic growth, but contrary to our hypothesis, the yolk sac has a compensatory capacity, being larger when the mothers are smaller; and the effect can be traced on fetal size at 24 weeks of gestation.
Asunto(s)
Índice de Masa Corporal , Desarrollo Embrionario/fisiología , Primer Trimestre del Embarazo/fisiología , Saco Vitelino , Adulto , Biometría/métodos , Composición Corporal , Correlación de Datos , Femenino , Desarrollo Fetal/fisiología , Peso Fetal , Edad Gestacional , Humanos , Embarazo , Atención Prenatal/métodos , Ultrasonografía Prenatal/métodos , Saco Vitelino/diagnóstico por imagen , Saco Vitelino/crecimiento & desarrolloAsunto(s)
Implantación del Embrión , Investigaciones con Embriones/ética , Investigaciones con Embriones/legislación & jurisprudencia , Desarrollo Embrionario , Modelos Biológicos , Investigación con Células Madre/ética , Investigación con Células Madre/legislación & jurisprudencia , Animales , Embrión de Mamíferos/citología , Embrión de Mamíferos/embriología , Femenino , Fertilización In Vitro , Humanos , Ratones , Placenta/citología , Placentación , Embarazo , Medicina Reproductiva/ética , Medicina Reproductiva/legislación & jurisprudencia , Medicina Reproductiva/tendencias , Biología Sintética/ética , Biología Sintética/legislación & jurisprudencia , Biología Sintética/tendencias , Saco Vitelino/citología , Saco Vitelino/crecimiento & desarrolloRESUMEN
Few studies report on the in vivo requirement for hematopoietic niche factors in the mammalian embryo. Here, we comprehensively analyze the requirement for Kit ligand (Kitl) in the yolk sac and aorta-gonad-mesonephros (AGM) niche. In-depth analysis of loss-of-function and transgenic reporter mouse models show that Kitl-deficient embryos harbor decreased numbers of yolk sac erythro-myeloid progenitor (EMP) cells, resulting from a proliferation defect following their initial emergence. This EMP defect causes a dramatic decrease in fetal liver erythroid cells prior to the onset of hematopoietic stem cell (HSC)-derived erythropoiesis, and a reduction in tissue-resident macrophages. Pre-HSCs in the AGM require Kitl for survival and maturation, but not proliferation. Although Kitl is expressed widely in all embryonic hematopoietic niches, conditional deletion in endothelial cells recapitulates germline loss-of-function phenotypes in AGM and yolk sac, with phenotypic HSCs but not EMPs remaining dependent on endothelial Kitl upon migration to the fetal liver. In conclusion, our data establish Kitl as a critical regulator in the in vivoAGM and yolk sac endothelial niche.
Asunto(s)
Desarrollo Embrionario/genética , Hematopoyesis/genética , Células Madre Hematopoyéticas/citología , Factor de Células Madre/genética , Animales , Aorta/crecimiento & desarrollo , Linaje de la Célula/genética , Proliferación Celular/genética , Células Endoteliales/citología , Células Endoteliales/metabolismo , Eritropoyesis/genética , Regulación del Desarrollo de la Expresión Génica/genética , Gónadas/crecimiento & desarrollo , Mesonefro/crecimiento & desarrollo , Ratones , Ratones Transgénicos , Nicho de Células Madre/genética , Saco Vitelino/crecimiento & desarrolloRESUMEN
Monocytes and macrophages are critical effectors and regulators of innate immune response. They not only play crucial and distinctive roles in homeostasis, but also contribute to some pathologic processes. The heterogeneity of the macrophage lineage has been widely recognized and, in part, is a result of the specialization of resident macrophages in particular tissue microenvironments. Monocytes are usually known to originate in the bone marrow from a common myeloid progenitor that is shared with neutrophils, and they are then released into the peripheral blood. However, the origin of tissue-resident macrophages, crucial for homeostasis and immunity, has remained controversial until recently. During embryonic organogenesis, macrophages derived from yolk sac and fetal liver precursors are seeded throughout tissues, persisting in the adulthood as resident, self-maintaining populations. After birth, bone marrow-derived monocytes can replenish tissue resident macrophages following injury, infection and inflammation. In this review, we will mainly summarize our current understanding on the origin, ontogeny and fates of tissue macrophages and will briefly discuss the molecular regulation of resident macrophage homeostasis in physiological situation.
Asunto(s)
Infecciones/inmunología , Inflamación/inmunología , Macrófagos/inmunología , Monocitos/inmunología , Células de la Médula Ósea/citología , Linaje de la Célula/genética , Linaje de la Célula/inmunología , Microambiente Celular/inmunología , Heterogeneidad Genética , Humanos , Inmunidad Innata/genética , Infecciones/genética , Infecciones/patología , Inflamación/genética , Inflamación/patología , Hígado/crecimiento & desarrollo , Hígado/inmunología , Macrófagos/citología , Monocitos/citología , Organogénesis/genética , Organogénesis/inmunología , Saco Vitelino/crecimiento & desarrollo , Saco Vitelino/inmunologíaRESUMEN
During avian embryonic development, endodermal epithelial cells (EECs) absorb yolk through the yolk sac membrane. Sterol O-acyltransferase (SOAT) is important for esterification and yolk lipid utilization during development. Because the major enzyme for yolk sac membrane cholesteryl ester synthesis is SOAT1, we cloned the avian SOAT1 promoter and elucidated the cellular functions of SOAT1. Treatments with either glucagon, isobutylmethylxanthine (IBMX), an adenylate cyclase activator (forskolin), a cAMP analog (dibutyryl-cAMP), or a low glucose concentration all increased SOAT1 mRNA accumulation in EECs from Japanese quail, suggesting that SOAT1 is regulated by nutrients and hormones through a cAMP-dependent pathway. Activity of protein kinase A (PKA) was increased by IBMX, whereas co-treatment with the PKA inhibitor, H89 negated the increase in PKA activity. Cyclic AMP-induced EECs had greater cholesterol esterification than untreated EECs. By promoter deletion and point-mutation, the cAMP-response element (-349 to -341 bp) was identified as critical in mediating transcription of SOAT1. In conclusion, expression of SOAT1 was regulated by a cAMP-dependent pathway and factors that increase PKA will increase SOAT1 to improve the utilization of lipids in the EECs and potentially modify embryonic growth.
Asunto(s)
Ésteres del Colesterol/metabolismo , Colesterol/metabolismo , Coturnix/embriología , Desarrollo Embrionario/genética , Animales , Membrana Celular/genética , Membrana Celular/metabolismo , Ésteres del Colesterol/genética , Coturnix/genética , AMP Cíclico/metabolismo , Endodermo/crecimiento & desarrollo , Endodermo/metabolismo , Células Epiteliales/metabolismo , Esterificación/genética , Glucagón/metabolismo , Hepatocitos/metabolismo , Regiones Promotoras Genéticas , Esterol O-Aciltransferasa/metabolismo , Saco Vitelino/crecimiento & desarrollo , Saco Vitelino/metabolismoRESUMEN
INTRODUCTION: Phylogenetics and genomics place colugos as the sister group to primates. Therefore their placentation is of interest in an evolutionary perspective. Previous accounts are fragmentary, not readily accessible and sometimes contradictory. METHODS: We have examined archival material covering the early development of fetal membranes and placenta, the fate of the yolk sac and definitive placentation. RESULTS: Initially the trophoblast extended over a rather broad but shallow area, enclosing maternal blood spaces. After expansion of the exocoelom it became covered by somatic mesoderm. The mature chorioallantoic placenta was haemochorial and characterized by a labyrinth with markedly dilated maternal blood spaces. Blood vessels appeared in the splanchnopleure early in development and later extended to the yolk sac, but we found no evidence of a choriovitelline placenta at any stage of gestation. There was, however, an extensive paraplacenta. CONCLUSIONS: A choriovitelline placenta is not formed early in gestation nor is it present at term. Early in development invasive trophoblast spreads laterally to form a trophoblastic plate. We found evidence to support the idea that the colugo placenta is intermediate between the labyrinthine placenta of rodents and the trabecular type of Neotropical primates.
Asunto(s)
Evolución Biológica , Euterios/fisiología , Placenta/anatomía & histología , Placentación , Saco Vitelino/crecimiento & desarrollo , Animales , Euterios/anatomía & histología , Femenino , EmbarazoRESUMEN
In rainbow trout, the dominant site of Na+ uptake (JNa,in) and ammonia excretion (Jamm) shifts from the skin to the gills over development. Post-hatch (PH; 7â days post-hatch) larvae utilize the yolk sac skin for physiological exchange, whereas by complete yolk sac absorption (CYA; 30â days post-hatch), the gill is the dominant site. At the gills, JNa,in and Jamm occur via loose Na+/NH4+ exchange, but this exchange has not been examined in the skin of larval trout. Based on previous work, we hypothesized that, contrary to the gill model, JNa,in by the yolk sac skin of PH trout occurs independently of Jamm Following a 12â h exposure to high environmental ammonia (HEA; 0.5â mmolâ l-1 NH4HCO3; 600â µmol l-1 Na+; pH 8), Jamm by the gills of CYA trout and the yolk sac skin of PH larvae, which were isolated using divided chambers, increased significantly. However, this was coupled to an increase in JNa,in across the gills only, supporting our hypothesis. Moreover, gene expression of proteins involved in JNa,in [Na+/H+-exchanger-2 (NHE2) and H+-ATPase] increased in response to HEA only in the CYA gills. We further identified expression of the apical Rhesus (Rh) proteins Rhcg2 in putative pavement cells and Rhcg1 (co-localized with apical NHE2 and NHE3b and Na+/K+-ATPase) in putative peanut lectin agglutinin-positive (PNA+) ionocytes in gill sections. Similar Na+/K+-ATPase-positive cells expressing Rhcg1 and NHE3b, but not NHE2, were identified in the yolk sac epithelium. Overall, our findings suggest that the mechanisms of JNa,in and Jamm by the dominant exchange epithelium at two distinct stages of early development are fundamentally different.
Asunto(s)
Amoníaco/metabolismo , Branquias/metabolismo , Oncorhynchus mykiss/metabolismo , Sodio/metabolismo , Saco Vitelino/metabolismo , Animales , Epitelio/crecimiento & desarrollo , Epitelio/metabolismo , Proteínas de Peces/metabolismo , Branquias/crecimiento & desarrollo , Larva/crecimiento & desarrollo , Larva/metabolismo , Oncorhynchus mykiss/crecimiento & desarrollo , ATPasas de Translocación de Protón/metabolismo , Piel/metabolismo , Intercambiadores de Sodio-Hidrógeno/metabolismo , ATPasa Intercambiadora de Sodio-Potasio/metabolismo , Saco Vitelino/crecimiento & desarrolloRESUMEN
Macrophages are key components of the innate immune system and play pivotal roles in immune response, organ development, and tissue homeostasis. Studies in mice and zebrafish have shown that tissue-resident macrophages derived from different hematopoietic origins manifest distinct developmental kinetics and colonization potential, yet the genetic programs controlling the development of macrophages of different origins remain incompletely defined. In this study, we use zebrafish, where tissue-resident macrophages arise from the rostral blood island (RBI) and ventral wall of dorsal aorta (VDA), the zebrafish hematopoietic tissue equivalents to the mouse yolk sac and aorta-gonad-mesonephros for myelopoiesis, to address this issue. We show that RBI- and VDA-born macrophages are orchestrated by distinctive regulatory networks formed by the E-twenty-six (Ets) transcription factors Pu.1 and Spi-b, the zebrafish ortholog of mouse spleen focus forming virus proviral integration oncogene B (SPI-B), and the helix-turn-helix DNA-binding domain containing protein Irf8. Epistatic studies document that during RBI macrophage development, Pu.1 acts upstream of Spi-b, which, upon induction by Pu.1, partially compensates the function of Pu.1. In contrast, Pu.1 and Spi-b act in parallel and cooperatively to regulate the development of VDA-derived macrophages. Interestingly, these two distinct regulatory networks orchestrate the RBI- and VDA-born macrophage development largely by regulating a common downstream gene, Irf8. Our study indicates that macrophages derived from different origins are governed by distinct genetic networks formed by the same repertoire of myeloid-specific transcription factors.
Asunto(s)
Linaje de la Célula/inmunología , Regulación del Desarrollo de la Expresión Génica , Redes Reguladoras de Genes , Macrófagos/inmunología , Proteínas Proto-Oncogénicas/inmunología , Transactivadores/inmunología , Pez Cebra/inmunología , Secuencia de Aminoácidos , Animales , Aorta/citología , Aorta/crecimiento & desarrollo , Aorta/inmunología , Diferenciación Celular , Linaje de la Célula/genética , Embrión no Mamífero , Humanos , Inmunidad Innata , Factores Reguladores del Interferón/genética , Factores Reguladores del Interferón/inmunología , Macrófagos/citología , Mesonefro/citología , Mesonefro/crecimiento & desarrollo , Mesonefro/inmunología , Ratones , Especificidad de Órganos , Isoformas de Proteínas/genética , Isoformas de Proteínas/inmunología , Proteínas Proto-Oncogénicas/genética , Proteínas Proto-Oncogénicas c-ets/genética , Proteínas Proto-Oncogénicas c-ets/inmunología , Transducción de Señal , Transactivadores/genética , Saco Vitelino/citología , Saco Vitelino/crecimiento & desarrollo , Saco Vitelino/inmunología , Pez Cebra/genética , Pez Cebra/crecimiento & desarrolloRESUMEN
Histomorphological changes in digestive tract of golden mahseer (Tor putitora) were examined in larvae [starting from hatching to 45 days post-hatching (dph)], fry, fingerling, and adult. Digestive tract appeared during hatching, on the dorsal side of yolk sac, as a straight tube with a narrow lumen. Mouth opening and appearance of liver and pancreas were observed at 2 dph, and subsequently anal opening, appearance of goblet cells in esophagus, and posterior intestine were evident at 3 dph. The remodeling of oral cavity in terms of epithelial stratification, appearance of taste buds, and goblet cells were observed in a window of 4-5 dph. Intestinal folding was found to be initiated at 8 dph. From 12 to 45 dph, thickening of oral and esophageal mucosal/extramucosal layers, increase in intestinal folding, increases in the density of goblet cells in entire gut were observed. Within the same time window, other histological changes such as disappearance of vacuoles in liver, and abundance of zymogen granules in pancreas were also observed. Supranuclear vesicles in mid-to-posterior intestine were found to be prominent from first feeding to 45 dph; however, this phenomenon was no longer evident in fry and fingerling. Overall, the increase in intestinal folding and complexity of extramucosal layer were found to be continuous from the first appearance to adult, and this inferred the fact that the nutritional physiology, in terms of digestion and assimilation, progressively changes throughout the life stages of golden mahseer. Findings of this study will, therefore, help in preparing diets for different life stages of this fish, and in addition, the present information widens the understanding of digestive physiology of golden mahseer.
Asunto(s)
Cyprinidae/crecimiento & desarrollo , Sistema Digestivo/crecimiento & desarrollo , Animales , Cyprinidae/anatomía & histología , Sistema Digestivo/anatomía & histología , Femenino , Larva/crecimiento & desarrollo , Masculino , Saco Vitelino/anatomía & histología , Saco Vitelino/crecimiento & desarrolloRESUMEN
The protein inhibitor of activated STAT-1 (PIAS1) is one of the few known SUMO E3 ligases. PIAS1 has been implicated in several biological processes including repression of innate immunity and DNA repair. However, PIAS1 function during development and tissue differentiation has not been studied. Here, we report that Pias1 is required for proper embryonic development. Approximately 90% of Pias1 null embryos die in utero between E10.5 and E12.5. We found significant apoptosis within the yolk sac (YS) blood vessels and concomitant loss of red blood cells (RBCs) resulting in profound anemia. In addition, Pias1 loss impairs YS angiogenesis and results in defective capillary plexus formation and blood vessel occlusions. Moreover, heart development is impaired as a result of loss of myocardium muscle mass. Accordingly, we found that Pias1 expression in primary myoblasts enhances the induction of cardiac muscle genes MyoD, Myogenin and Myomaker. PIAS1 protein regulation of cardiac gene transcription is dependent on transcription factors Myocardin and Gata-4. Finally, endothelial cell specific inactivation of Pias1 in vivo impairs YS erythrogenesis, angiogenesis and recapitulates loss of myocardium muscle mass. However, these defects are not sufficient to recapitulate the lethal phenotype of Pias1 null embryos. These findings highlight Pias1 as an essential gene for YS erythropoiesis and vasculogenesis in vivo.