Snail promotes the cell-autonomous generation of Flk1(+) endothelial cells through the repression of the microRNA-200 family.

Expression of the transcription factor Snail is required for normal vasculogenesis in the developing mouse embryo. In addition, tumors expressing Snail have been associated with a more malignant phenotype, with both increased invasive properties and angiogenesis. Although the relationship between Snail and vasculogenesis has been noted, no mechanistic analysis has been elucidated. Here, we show that in addition to inducing an epithelial mesenchymal transition, Snail promotes the cell-autonomous induction of Flk1(+) endothelial cells in an early subset of differentiating mouse embryonic stem (ES) cells. Cells that become Flk1+ in response to Snail have a transcriptional profile specific to Gata6+primitive endoderm, but not the early Nanog+epiblast. We further show that Snail's ability to promote Flk1(+) endothelium depends on fibroblast growth factor signaling as well as the repression of the microRNA-200 (miR-200) family, which directly targets the 3' UTRs of Flk1 and Ets1. Together, our results show that Snail is capable of inducing Flk1+ lineage commitment in a subset of differentiating ES cells through the down-regulation of the miR-200 family. We hypothesize that this mechanism of Snail-induced vasculogenesis may be conserved in both the early developing embryo and malignant cancers.

Germinal matrix hemorrhage of prematurity: treatment approaches and outcomes in a single institutional review in the Ukraine.

OBJECTIVE: To review the treatment outcome of germinal matrix hemorrhage (GMH) in premature infants in a single Ukrainian institution in an effort to determine optimal diagnostic and therapeutic approaches. MATERIALS AND METHODS: Eight hundred and thirty-five premature newborns (gestational age 33.0 +/- 2.50 weeks, birth weight 2,124.81 +/- 282.54 g; mean +/- SD) were examined for the development of perinatal hypoxic-ischemia injury and asphyxia condition. This research focuses on various types of massive intracranial hemorrhage (ICH) and posthemorrhagic hydrocephalus (PHH). The diagnostic methods were based on intracranial imaging studies and clinical features that are present at birth. The therapeutic and preventive strategies consist of parental counseling, supportive and rehabilitative care for affected infants. Surgical intervention was indicated for the prevention and treatment of severe PHH. Thirty-four preterm infants were treated by ventricular-peritoneal/subgaleal shunting with close monitoring of intracerebral pressure. RESULTS: Massive GMH took place at 32-35 gestational weeks as a result of increased periventricular anastomosis. GMH was unusual in full-term newborns, whereas cerebral hypoxic-ischemic injuries were more common in full-term neonates. Approximately 98% of premature infants with low birth weight survived and 2% died due to respiratory distress syndrome and other complications. ICH which occurs in neonates at 24-28 gestational weeks was mainly due to immature vascular walls and insufficiency of vascular anastomosis at the germinal matrix. CONCLUSIONS: ICH occurring in the germinal matrix of premature newborns is closely related to the development of the brain vasculature. Evacuation of the hematoma is more detrimental than beneficial, despite the rapid strides being taken to keep low-birth weight premature infants alive. Therefore, the treatment of ICH and PHH requires a fundamental understanding of pathogenetic changes, which is necessary for the neurorehabilitation and immediate elimination of cerebral compression and its complications.

An immunocytochemical study of the germinal layer vasculature in the developing fetal brain using Ulex europaeus 1 lectin.

The characteristics of the germinal matrix vasculature were studied in the developing fetal brain using immunocytochemical methods. A preliminary comparative immunocytochemical study was made on six fetal brains to compare endothelial staining by Ulex europaeus I lectin with that of antibody to Factor VIII related antigen. Ulex was found to stain germinal layer vessels better than Factor VIII related antigen. Subsequently, the germinal layers of a further 15 fetal and preterm infant brains ranging from 13 to 35 weeks' gestation were stained with Ulex europaeus I to demonstrate the vasculature. With increasing gestation, there was a gradual increase in vessel density, particularly of capillaries. This was not a uniform process. A plexus of capillaries was prominent immediately beneath the ependyma while the more central parts of the germinal matrix contained fewer, but often larger diameter, vessels. The variation in vessel density which was a feature of the later gestation brains may have implications for local blood flow and may be a factor in haemorrhage at this site.

Vasculature to the germinal matrix in rabbit pups.

The authors report a study of the cerebral vasculature of premature rabbits pertaining to the germinal matrix (GM). A pigmented silicone material (Microfil) was injected into the carotid artery of anesthetized rabbits. Methyl methacrylate vascular casts of a similar group of premature rabbits were examined by scanning electron microscopy. The GM is supplied by arteries from both the basal and convexity surfaces of the brain. Vessels could be identified as arteries or veins by their typical patterns of branching and by the characteristic impressions made on the methyl methacrylate casts by endothelial nuclei. Specific evidence of structural weaknesses in the vasculature, which could be a site of predilection for GM bleeding, was not observed. The similarities in basal ganglia vasculature between premature rabbits and humans justifies using the rabbit model to study vascular aspects of the GM and intraventricular hemorrhage.