419ABSTRACTS / Developmental Biology 306 (2007) 411–426

hypercellular epicardium with abundant subepicardial mesench-yme and a thin compact zone myocardium. Tgfbr3 null micealso displayed other defects in coronary development includingdysmorphic and distended vessels along the AV groove andsubepicardial hemorrhage. In null mice, vessels throughout theyolk sac and embryo form and recruit smooth muscle in a patternindistinguishable from heterozygous or wild type littermates.These data demonstrate a requirement for Tgfbr3 during coro-nary vessel development that is essential for embryonic viability.

Source: HL67105(JVB), AHA0655129(JVB), and GM07347(LAC).

doi:10.1016/j.ydbio.2007.03.648

Program/Abstract # 357Analysis of cardiovascular anomalies in the Ts65Dn mousemodel for Down syndromeAustin D. Williams, Clara S. MooreDepartment of Biology, Franklin and Marshall College,Lancaster, PA, USA

The Ts65Dn mouse is the most-studied murine model forDown syndrome (DS) or trisomy 21. Homology betweentriplicated murine genes and genes on human chromosome 21(Hsa21) correlates with the shared anomalies of Ts65Dn miceand DS patients. Congenital heart defects occur in approxi-mately 50 percent of DS individuals and we have worked tocharacterize cardiovascular anomalies observed in Ts65Dnneonates. Vascular abnormalities were identified in 17 percentof trisomic neonates by examination of gross anatomy.We foundright aortic arch with Kommerell's diverticulum, interruptedaortic arch and persistent truncus arteriosis. Intracardiac defectswere detected using staining with hemotoxylin and eosin, andMasson's trichrome. We have identified interventricular sepaldefects and broad foramen ovale in trisomic neonates.Additionally, immunohistochemistry indicates abnormal musclecomposition in the cardiac valves of trisomic neonates. Thesefindings suggest that the gene imbalance in Ts65Dn disruptscrucial pathways in cardiac development.

doi:10.1016/j.ydbio.2007.03.649

Program/Abstract # 358Guidance molecules in organogenesis: Slit signaling inDrosophila hindgut developmentNadine H. Soplop, Edgardo Santiago-Martínez,Sunita G. KramerPathology Department, University of Medicine and Dentistryof New Jersey at Robert Wood Johnson Medical School,Piscataway, NJ

The alimentary canal in the Drosophila embryo iscomprised of three regions, the foregut, midgut and hindgut.

The most posterior section, the hindgut, forms by invaginationof ectoderm, DNA endoreplication and convergent extension.The hindgut is subdivided into the small intestine, largeintestine and rectum. The large intestine contains threemorphologically and molecularly distinct cell populations.These are described as dorsal, ventral and boundary cells. Thepresence of guidance cues that lead migrating cells to theirpoints of attachment has been shown in the CNS and somaticmuscle systems in Drosophila. Specifically, the ECM protein,Slit, and Roundabout (Robo) family of receptors function inboth systems to repel the migrating cells. Slit, Robo andRobo2 are also expressed in the hindgut. At this time indevelopment, the cells of the hindgut have already beendetermined. Dorsal, ventral and boundary cells are correctlyspecified in slit loss of function mutants as shown byimmunohistochemical stainings using cell-specific markers.Moreover, in slit loss of function mutants, lumen defects aswell as defects in overall cell shape are seen using EM andimmunohistochemistry. We suggest a novel role for Slit inlumen formation and cell shape regulation in the Drosophilahindgut.

doi:10.1016/j.ydbio.2007.03.650

Program/Abstract # 359A non-canonical Wnt pathway mediated by Wnt5a isrequired for midgut elongationSara Cervantes 1, Terry P. Yamaguchi 2, Matthias Hebrok 1

1 Diabetes Center, Dept. of Medicine, University of CaliforniaSan Francisco, San Francisco, CA, USA2 Cancer and Developmental Biology Laboratory, Center forCancer Research, NCI-Frederick, Frederick, MD, USA

Several morphogenetic processes that occur during mousedevelopment involve tissue elongation. At embryonic day10.5, the midgut area of the gastrointestinal tract starts toelongate along the anterior-posterior axis forming a loop thatwill herniate outside the abdominal cavity around embryonicday 13.5. The scarcity of knowledge regarding the molecularand cellular basis of this morphogenetic process prompted usto identify the signaling pathways required for midgutelongation. Here, we show that Wnt5a, a non-canonical Wntligand, is expressed in the gut at the onset of midgutelongation in a restricted pattern. Mice deficient in Wnt5ashow multiple malformations in the gastrointestinal tractincluding a dramatic shortening of the small intestine.Interestingly, the remaining intestinal tissue does not showany defects in differentiation by embryonic day 18.5. Closerinspection of the phenotype showed that instead of elongatingand forming a ventral loop, the midgut forms a bifurcatedlumen which grows parallel to the main branch. Additionalresults indicate that neither the Wnt/Planar Cell Polarity norWnt/β-catenin pathways are involved in Wnt5a functionduring midgut elongation. Our results demonstrate thatWnt5a is required for the elongation of thesmall intestine