Severe Malformations (severe + malformation)

Distribution by Scientific Domains

Selected Abstracts

Patterning the embryonic kidney: BMP signaling mediates the differentiation of the pronephric tubules and duct in Xenopus laevis

Christina M. Bracken
Abstract The Bone morphogenetic proteins (BMPs) mediate a wide range of diverse cellular behaviors throughout development. Previous studies implicated an important role for BMP signaling during the differentiation of the definitive mammalian kidney, the metanephros. In order to examine whether BMP signaling also plays an important role during the patterning of earlier renal systems, we examined the development of the earliest nephric system, the pronephros. Using the amphibian model system Xenopus laevis, in combination with reagents designed to inhibit BMP signaling during specific stages of nephric development, we revealed an evolutionarily conserved role for this signaling pathway during renal morphogenesis. Our results demonstrate that conditional BMP inhibition after specification of the pronephric anlagen is completed, but prior to the onset of morphogenesis and differentiation of renal tissues, results in the severe malformation of both the pronephric duct and tubules. Importantly, the effects of BMP signaling on the developing nephron during this developmental window are specific, only affecting the developing duct and tubules, but not the glomus. These data, combined with previous studies examining metanephric development in mice, provide further support that BMP functions to mediate morphogenesis of the specified renal field during vertebrate embryogenesis. Specifically, BMP signaling is required for the differentiation of two types of nephric structures, the pronephric tubules and duct. Developmental Dynamics 237:132,144, 2008. © 2007 Wiley-Liss, Inc. [source]

Association between X-linked lissencephaly with ambiguous genitalia syndrome and lenticulostriate vasculopathy in neonate

Mateusz Jag
Abstract X-linked lissencephaly with ambiguous genitalia syndrome (XLAG) (OMIM #3000215) is a rare, severe malformation of the brain cortex with abnormal neuronal migration caused by mutations of the ARX gene. All the reported patients with lissencephaly are males who presented with a posterior-to-anterior gradient, moderately increased thickness of the brain cortex, agenesis of corpus callosum, micropenis, and cryptorchidism. We describe the neurosonographic findings associated with the XLAG syndrome. To our knowledge, the association between XLAG and lenticulostriate vasculopathy has not been reported before. © 2008 Wiley Periodicals, Inc. J Clin Ultrasound, 2008 [source]

Genetic disruption of CYP26B1 severely affects development of neural crest derived head structures, but does not compromise hindbrain patterning

Glenn Maclean
Abstract Cyp26b1 encodes a cytochrome-P450 enzyme that catabolizes retinoic acid (RA), a vitamin A derived signaling molecule. We have examined Cyp26b1,/, mice and report that mutants exhibit numerous abnormalities in cranial neural crest cell derived tissues. At embryonic day (E) 18.5 Cyp26b1,/, animals exhibit a truncated mandible, abnormal tooth buds, reduced ossification of calvaria, and are missing structures of the maxilla and nasal process. Some of these abnormalities may be due to defects in formation of Meckel's cartilage, which is truncated with an unfused distal region at E14.5 in mutant animals. Despite the severe malformations, we did not detect any abnormalities in rhombomere segmentation, or in patterning and migration of anterior hindbrain derived neural crest cells. Abnormal migration of neural crest cells toward the posterior branchial arches was observed, which may underlie defects in larynx and hyoid development. These data suggest different periods of sensitivity of anterior and posterior hindbrain neural crest derivatives to elevated levels of RA in the absence of CYP26B1. Developmental Dynamics 238:732,745, 2009. © 2009 Wiley-Liss, Inc. [source]

A mouse model for cystic biliary dysgenesis in autosomal recessive polycystic kidney disease (ARPKD),

HEPATOLOGY, Issue 5 2005
Markus Moser
Autosomal recessive polycystic kidney disease (ARPKD) is an important cause of liver- and renal-related morbidity and mortality in childhood. Recently, PKHD1, the gene encoding the transmembrane protein polyductin, was shown to be mutated in ARPKD patients. We here describe the first mouse strain, generated by targeted mutation of Pkhd1. Due to exon skipping, Pkhd1ex40 mice express a modified Pkhd1 transcript and develop severe malformations of intrahepatic bile ducts. Cholangiocytes maintain a proliferative phenotype and continuously synthesize TGF-,1. Subsequently, mesenchymal cells within the hepatic portal tracts continue to synthesize collagen, resulting in progressive portal fibrosis and portal hypertension. Fibrosis did not involve the hepatic lobules, and we did not observe any pathological changes in morphology or function of hepatocytes. Surprisingly and in contrast to human ARPKD individuals, Pkhd1ex40 mice develop morphologically and functionally normal kidneys. In conclusion,our data indicate that subsequent to formation of the embryonic ductal plate, dysgenesis of terminally differentiated bile ducts occurs in response to the Pkhd1ex40 mutation. The role of polyductin in liver and kidney may be functionally divergent, because protein domains essential for bile duct development do not affect nephrogenesis in our mouse model. Supplementary material for this article can be found on the HEPATOLOGYwebsite ( (HEPATOLOGY 2005.) [source]

Mutagenicity and Safety Evaluation of Water Extract of,Coriander sativum,Leaves

Mariana Ramírez Reyes
ABSTRACT:, Coriander has been used as a spice and medicinal plant for centuries. Several studies have described its biological properties and some reports have indicated its pharmacological actions in some human pathology. However, data on its toxicity and metabolism are limited or null, and no research has been conducted with mammalian cells. The purpose of this study was to evaluate the mutagenicity and safety of,Coriandrum sativum,extract. The mutagenic effects of,C. sativum,extract were evaluated by Ames test. Mutagenicity was present when the,C. sativum,extract was used in high concentrations in both tested strains (Salmonella typhimurium,TA97 and TA102). Our research showed that,C. sativum,extract reduced the cell survival of human cell lines (WRL-68 and 293Q cells) by inducing apoptosis and necrosis in the cases where extract concentration was the highest. The,C. sativum,extract altered the cell cycle; it increased the G1 phase of hepatic cells and reduced the G2+M phase in both cell lines in a dose-response manner. These results showed correlation with a reduction in the mitotic index. The extract also induced severe malformations during embryonic development. Exposure of chicken embryos to the,C. sativum,extract resulted in a dose-dependent increase of anomalies. Present results show that,C. sativum,extract reduced the axial skeleton and affected the neural tube, the somites, the cardiovascular structures, and the eye. According to the present results, the,C. sativum,aqueous extract cannot be considered safe. These results indicate that some significant adverse effects of,C. sativum,extract could be observed,in vivo. [source]