The fate of the vitelline and umbilical veins during the development of the human liver.

Differentiation of endodermal cells into hepatoblasts is well studied, but the remodeling of the vitelline and umbilical veins during liver development is less well understood. We compared human embryos between 3 and 10 weeks of development with pig and mouse embryos at comparable stages, and used Amira 3D reconstruction and Cinema 4D remodeling software for visualization. The vitelline and umbilical veins enter the systemic venous sinus on each side via a common entrance, the hepatocardiac channel. During expansion into the transverse septum at Carnegie Stage (CS)12 the liver bud develops as two dorsolateral lobes or 'wings' and a single ventromedial lobe, with the liver hilum at the intersection of these lobes. The dorsolateral lobes each engulf a vitelline vein during CS13 and the ventromedial lobe both umbilical veins during CS14, but both venous systems remain temporarily identifiable inside the liver. The dominance of the left-sided umbilical vein and the rightward repositioning of the sinuatrial junction cause de novo development of left-to-right shunts between the left umbilical vein in the liver hilum and the right hepatocardiac channel (venous duct) and the right vitelline vein (portal sinus), respectively. Once these shunts have formed, portal branches develop from the intrahepatic portions of the portal vein on the right side and the umbilical vein on the left side. The gall bladder is a reliable marker for this hepatic vascular midline. We found no evidence for large-scale fragmentation of embryonic veins as claimed by the 'vestigial' theory. Instead and in agreement with the 'lineage' theory, the vitelline and umbilical veins remained temporally identifiable inside the liver after being engulfed by hepatoblasts. In agreement with the 'hemodynamic' theory, the left-right shunts develop de novo.

Patterning mechanisms of the sub-intestinal venous plexus in zebrafish.

Despite considerable interest in angiogenesis, organ-specific angiogenesis remains less well characterized. The vessels that absorb nutrients from the yolk and later provide blood supply to the developing digestive system are primarily venous in origin. In zebrafish, these are the vessels of the Sub-intestinal venous plexus (SIVP) and they represent a new candidate model to gain an insight into the mechanisms of venous angiogenesis. Unlike other vessel beds in zebrafish, the SIVP is not stereotypically patterned and lacks obvious sources of patterning information. However, by examining the area of vessel coverage, number of compartments, proliferation and migration speed we have identified common developmental steps in SIVP formation. We applied our analysis of SIVP development to obd mutants that have a mutation in the guidance receptor PlexinD1. obd mutants show dysregulation of nearly all parameters of SIVP formation. We show that the SIVP responds to a unique combination of pathways that control both arterial and venous growth in other systems. Blocking Shh, Notch and Pdgf signaling has no effect on SIVP growth. However Vegf promotes sprouting of the predominantly venous plexus and Bmp promotes outgrowth of the structure. We propose that the SIVP is a unique model to understand novel mechanisms utilized in organ-specific angiogenesis.

Imaging of omphalomesenteric duct remnants and related pathologies in children.

The omphalomesenteric duct (OMD) or the vitelline duct (VD) is the embryologic communication between the yolk sac and the primitive midgut. OMD or VD anomalies are a group of defects resulting from failure of involution of the OMD. Meckel diverticulum is the most common anomaly that results from failure of resorption of the OMD. Other less common anomalies seen in children include OMD fibrous band, fistula, sinus tract, cyst, and umbilical polyps. These OMD remnants can have variable clinical manifestations such as umbilical discharge, small bowel obstruction, gastrointestinal tract bleeding, or acute abdomen. This pictorial essay reviews the clinical presentation and imaging findings of the common and not so common complications of OMD remnants in the pediatric population.

Mouse extraembryonic arterial vessels harbor precursors capable of maturing into definitive HSCs.

During mouse development, definitive hematopoietic stem cells (dHSCs) emerge by late E10.5 to E11 in several hematopoietic sites. Of them, the aorta-gonad-mesonephros (AGM) region drew particular attention owing to its capacity to autonomously initiate and expand dHSCs in culture, indicating its key role in HSC development. The dorsal aorta contains characteristic hematopoietic clusters and is the initial site of dHSC emergence, where they mature through vascular endothelial (VE)-cadherin(+)CD45(-)CD41(low) (type 1 pre-HSCs) and VE-cadherin(+)CD45(+) (type 2 pre-HSCs) intermediates. Although dHSCs were also found in other embryonic niches (placenta, yolk sac, and extraembryonic vessels), attempts to detect their HSC initiating potential have been unsuccessful to date. Extraembryonic arterial vessels contain hematopoietic clusters, suggesting that they develop HSCs, but functional evidence for this has been lacking. Here we show that umbilical cord and vitelline arteries (VAs), but not veins, contain pre-HSCs capable of maturing into dHSCs in the presence of exogenous interleukin 3, although in fewer numbers than the AGM region, and that pre-HSC activity in VAs increases with proximity to the embryo proper. Our functional data strongly suggest that extraembryonic arteries can actively contribute to adult hematopoiesis.

Pathogenic implications of remnant vitelline structures in gastroschisis.

PURPOSE: The pathogenesis of gastroschisis is unknown. It may be helpful in understanding its pathogenesis to know the structural relationships among umbilical components including umbilical vessels, urachus, and vitelline structures, and thus, the authors investigated the remnants of vitelline structures in a series of cases of gastroschisis. METHODS: Medical records of 41 cases with gastroschisis treated in our institute from 1979 to 2009 were retrospectively reviewed. RESULTS: Paraumbilical bands, possible remnants of vitelline structures, were observed in 4 cases (9.8%). All 4 bands were attached to the skin edge of the abdominal defect without incorporation into the umbilical cord. The band ended at the mesentery in 3 cases and at the antimesenteric site of the ileum in the remaining case. Histologic findings showed fibrous tissues in all cases. One was possibly associated with the development of colonic atresia. Another was noticed after silo reduction when herniated bowels became strangulated by the band. The other 2 cases were uncomplicated. CONCLUSIONS: Our findings may support the recently proposed hypothesis that the developmental failure of the yolk sac and related vitelline structures to merge with or to be incorporated into the umbilical stalk might be associated with the pathogenesis of the abdominal wall defect in gastroschisis. Paraumbilical bands derived from vitelline structures may possibly cause intestinal ischemia prenatally or postnatally.

Three-dimensional cartography of hematopoietic clusters in the vasculature of whole mouse embryos.

Hematopoietic cell clusters in the aorta of vertebrate embryos play a pivotal role in the formation of the adult blood system. Despite their importance, hematopoietic clusters have not been systematically quantitated or mapped because of technical limitations posed by the opaqueness of whole mouse embryos. Here, we combine an approach to make whole mouse embryos transparent, with multicolor marking, to allow observation of hematopoietic clusters using high-resolution 3-dimensional confocal microscopy. Our method provides the first complete map and temporal quantitation of all hematopoietic clusters in the mouse embryonic vasculature. We show that clusters peak in number at embryonic day 10.5, localize to specific vascular subregions and are heterogeneous, indicating a basal endothelial to non-basal (outer cluster) hematopoietic cell transition. Clusters enriched with the c-Kit(+)CD31(+)SSEA1(-) cell population contain functional hematopoietic progenitors and stem cells. Thus, three-dimensional cartography of transparent mouse embryos provides novel insight into the vascular subregions instrumental in hematopoietic progenitor/stem cell development, and represents an important technological advancement for comprehensive in situ hematopoietic cluster analysis.

Escape of the yolk sac: a hypothesis to explain the embryogenesis of gastroschisis.

Gastroschisis is a significant birth defect that in many countries has shown an increased prevalence in recent decades, and the change has affected primarily younger mothers. Despite numerous epidemiological studies no other consistent associated risk factor has been identified. In this paper we review the five main theories related to the pathogenesis of this malformation and outline the reasons why we think none fully explains the embryogenesis of gastroschisis. We briefly present some clinical observations we have made that we consider germane to the pathogenesis and outline a hypothesis that we think can account for the origins of this malformation. Our proposal is that the determining defect in gastroschisis is failure of the yolk sac and related vitelline structures to be incorporated into the umbilical stalk. Otherwise, ventral closure of the lateral abdominal walls occurs normally, thus orphaning the vitelline duct and yolk sac outside both the main body stalk and the abdominal wall. Thus, in addition to the umbilicus, the abdominal wall has a separate perforation through which the midpoint of the gut is attached to the exteriorized vitelline structures. This connection through the ventral wall prevents normal egress of the gut into the umbilical cord during the second month of development and acts as the egress point for the gut resulting in gastroschisis.

Carbimazole embryopathy-bilateral choanal atresia and patent vitello-intestinal duct: a case report and review of literature.

BACKGROUND: In utero exposure to carbimazole for maternal hyperthyroidism has been reported to cause choanal atresia. There are case reports of patent vitello-intestinal duct and Meckel's diverticulum in similar association. CASE: We report another such instance of an infant who was exposed to carbimazole in utero, presenting with bilateral choanal atresia and patent vitello-intestinal duct. CONCLUSIONS: As there seems to be no reports of a possible association between propylthiouracil and congenital malformations, it may be safer to use propylthiouracil instead of carbimazole.

A case report of an omphalopagus heteropagus (parasitic) twin.

Heteropagus twin refers to a type of conjoined twin in which an incomplete smaller (parasitic) twin is attached to and dependent upon an otherwise normal host twin. The majority of cases have complete or partial duplication of the pelvis and/or lower extremities. The case depicted herein is unusual in that only isolated case reports have described an attached amorphous mass without identifiable limbs.

Intrauterine omphalic ileal entrapment as an unusual cause of ileal atresia: report of a case.

We report a case of ileal atresia (IA) caused by an omphalic ring closure anomaly. A 2-day-old male neonate started vomiting bile, accompanied by abdominal distention. Laparotomy revealed that the distal part of the ileum was entrapped within the omphalic ring and that this entrapped segment of ileum was atretic. To our knowledge, this potential mechanism of IA has not been described before.

In ovo vitelline duct ligation results in transient changes of bursal microenvironments.

The avian bursa of Fabricius has a direct connection to the cloaca via the bursal duct. Using the bursal duct ligation technique, it has been clearly shown that the B cells of the bursal follicles develop under the influence of cloacal antigens. These antigens have been suggested to be present on the bursal secretory dendritic cells in immunoglobulin G (IgG)-containing complexes. We studied the effect of maternal (yolk) antigens on the early development of B cells and the appearance of IgG-containing complexes of the bursal dendritic cells with a novel embryo manipulation technique, in ovo vitelline duct ligation. This operation blocked the direct (intestinal) transport of yolk substances into the intestine, but left the vitelline circulation intact. Vitelline duct ligation performed on embryonic day 17 resulted in serious but transient bursal underdevelopment during the first week of life: (1) IgG and the follicular dendritic cell marker 74.3 were not detectable on the bursal secretory dendritic cells, in spite of a normal serum IgG level and free communication with the cloacal lumen; (2) the number of B cells in the follicles was greatly reduced and they showed an altered phenotype, resembling that of the prebursal B cells. The intracloacal administration of different proteins effectively restored the bursal phenotype. These data suggest that maternal antigens indirectly help the maturation of bursal secretory dendritic cells and concomitantly that of B cells during the first week of life.

A study of the anatomic features of the duct of the urachus.

The urachus is an embryonic remnant resulting from involution of the allantoic duct and the ventral cloaca. Attaching the bladder dome to the umbilicus, this duct becomes progressively obliterated during fetal life. It may subsequently persist as different variants after birth, some regarded as normal, others as pathologic, due to incomplete closure. Six pediatric cases are reported here, and the literature on the embryology and anatomic basis of the duct is discussed. The urachus is present in nearly 100% of children at birth, with several possible shapes: tubular, fusiform or funnel. It gradually regresses and is found in only a third of adults. Its length varies from 1 to 15 cm. In our series 6 patients showed defective closure of the duct, including 3 with complete patency, 1 cyst, 1 diverticulum and 1 external sinus. Although rare, congenital pathology of the urachus requires a sound knowledge of the anatomy and embryology to distinguish normal forms from those subject to complications. It should be suspected with any lesion in the umbilical region and the appropriate treatment instituted.

Pólipos umbilicales y otras anomalías del conducto onfalomesentérico / Umbilical polyps and other abnormalities of the omphalomesenteric duct

El conducto onfalomesentérico es una estructura tubular que une el intestino primitivo con el saco vitelino del embrión. Normalmente esta estructura desaparece obliterándose completamente al final de la 5º o 6º semana de vida intrauterina, pero en ocasiones puede persistir ocasionando diferentes anomalías como fístulas, quistes vitelinos o pólipos umbilicales. Los pólipos son lesiones tumorales rojo brillante que se observan en la cicatriz umbilical tras la caída del cordón.Se presentan 10 casos de anomalías del cierre del conducto onfalomesentérico, de los cuales 7 fueron varones y 3 mujeres. 9 pacientes presentaron pólipos umbilicales, 2 de ellos con fístulas enterocutáneas, y una paciente un quiste vitelino. Las edades de consulta fueron desde los 4 días de vida hasta los 6 años de edad. En 8 pacientes se realizaron estudios histopatológicos, que evidenciaron mucosa gastrointestinal en contacto con epidermis, en 2 casos se realizaron estudios por imágenes contrastadas, encontrándose fístulas enterocutáneas, y en uno fue necesaria una laparotomía exploradora para llegar al diagnóstico. Es importante conocer estas anomalías umbilicales ya que por su embriogénesis, pueden asociarse con alguna de las otras alteraciones derivadas de la falla del cierre del conducto onfalomesentérico, las cuales pueden ocasionar consecuencias graves para el paciente, de no realizarse el diagnóstico oportuno y el tratamiento correcto (AU)

[A bizarre excrescence of the umbilicus in a 1-month-old child]. / Une excroissance bizarre de l'ombilic chez un enfant de un mois.

We report the case of an umbilical polyp, derived from omphalo-mesenteric remnants in an one-month-old female child. This rare abnormality results from a closure defect of the vitelline duct. The vitelline duct normally closes between the 5th and the 7th weeks of intra embryonic development but can lead to several pathologies in case of closure defects, giving rise to abdominal (Meckel diverticulum, vitelline cyst) or umbilical symptoms (umbilical fistula, umbilical sinus and umbilical polyp). These disorders have a 2% incidence, and may induce clinical symptoms of varied gravity ranging from clinical silence to acute abdomen. We seized the opportunity of this rare clinical observation to review the nosology of vitelline duct defects at the light of embryologic data.