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A heterozygous nonsense variant was identified in dapper, antagonist of beta-catenin, 1 (DACT1) via whole-exome sequencing in family members with imperforate anus, structural renal abnormalities, genitourinary anomalies, and/or ear anomalies. The DACT1 c.1256G>A;p.Trp419 * variant segregated appropriately in the family consistent with an autosomal dominant mode of inheritance. DACT1 is a member of the Wnt-signaling pathway, and mice homozygous for null alleles display multiple congenital anomalies including absent anus with blind-ending colon and genitourinary malformations. To investigate the DACT1 c.1256G>A variant, HEK293 cells were transfected with mutant DACT1 cDNA plasmid, and immunoblotting revealed stability of the DACT1 p.Trp419 * protein. Overexpression of DACT1 c.1256G>A mRNA in Xenopus embryos revealed a specific gastrointestinal phenotype of enlargement of the proctodeum. Together, these findings suggest that the DACT1 c.1256G>A nonsense variant is causative of a specific genetic syndrome with features overlapping Townes-Brocks syndrome., (© 2017 WILEY PERIODICALS, INC.)

Pancreas-specific transcription factor 1a (Ptf1a), a bHLH transcription factor, has two temporally distinct functions during pancreas development; initially it is required for early specification of the entire pancreas, while later it is required for proper differentiation and maintenance of only acinar cells. The importance of Ptf1a function was revealed by the fact that loss of Ptf1a leads to pancreas agenesis in humans. While Ptf1a is one of the most important pancreatic transcription factors, little is known about the differences between the regulatory networks it controls during initial specification of the pancreas as opposed to acinar cell development, and to date no comprehensive analysis of its downstream targets has been published. In this article, we use Xenopus embryos to identify putative downstream targets of Ptf1a. We isolated anterior endoderm tissue overexpressing Ptf1a at two early stages, NF32 and NF36, and compared their gene expression profiles using microarrays. Our results revealed that Ptf1a regulates genes with a wide variety of functions, providing insight into the complexity of the regulatory network required for pancreas specification., (Copyright © 2012 Wiley Periodicals, Inc.)

Xenopus is an essential vertebrate model system for biomedical research that has contributed to important discoveries in many disciplines, including cell biology, molecular biology, physiology, developmental biology, and neurobiology. However, unlike other model systems no central repository/stock center for Xenopus had been established until recently. Similar to mouse, zebrafish, and fly communities, which have established stock centers, Xenopus researchers need to maintain and distribute rapidly growing numbers of inbred, mutant, and transgenic frog strains, along with DNA and protein resources, and individual laboratories struggle to accomplish this efficiently. In the last 5 years, two resource centers were founded to address this need: the European Xenopus Resource Center (EXRC) at the University of Portsmouth in England, and the National Xenopus Resource (NXR) at the Marine Biological Laboratory in Woods Hole, MA. These two centers work together to provide resources and support to the Xenopus research community. The EXRC and NXR serve as stock centers and acquire, produce, maintain and distribute mutant, inbred and transgenic Xenopus laevis and Xenopus tropicalis lines. Independently, the EXRC is a repository for Xenopus cDNAs, fosmids, and antibodies; it also provides oocytes and wild-type frogs within the United Kingdom. The NXR will complement these services by providing research training and promoting intellectual interchange through hosting mini-courses and workshops and offering space for researchers to perform short-term projects at the Marine Biological Laboratory. Together the EXRC and NXR will enable researchers to improve productivity by providing resources and expertise to all levels, from graduate students to experienced PIs. These two centers will also enable investigators that use other animal systems to take advantage of Xenopus' unique experimental features to complement their studies., (Copyright © 2012 Wiley Periodicals, Inc.)

Defining the regulatory molecular networks involved in patterning the developing anterior endoderm is essential to understand how the pancreas, liver, stomach, and duodenum are discretely specified from each other. In this study, we analyzed the expression and function of the double-stranded RNA-binding protein Staufen2 in Xenopus laevis endoderm. We found that staufen2 was broadly expressed within the developing endoderm beginning at gastrulation becoming localized to the anterior endoderm at later stages. Through morpholino-mediated knockdown, we demonstrate that Staufen2 function is required for proper formation of the stomach, liver, and pancreas. We define that its function is required during gastrulation for proper patterning of the dorsal-ventral axis and that it acts to regulate expression of BMP signaling components., (Copyright © 2011 Wiley Periodicals, Inc.)