Intestinal alkaline phosphatase administration in newborns is protective of gut barrier function in a neonatal necrotizing enterocolitis rat model.

Background: Previously, we have shown that supplementation of intestinal alkaline phosphatase (IAP) decreased severity of necrotizing enterocolitis (NEC)-associated intestinal injury. We hypothesized that IAP administration is protective of intestinal epithelial barrier function in a dose-dependent manner.

Methods: Control rat pups were vaginally delivered and breast-fed.

Making a definitive diagnosis: successful clinical application of whole exome sequencing in a child with intractable inflammatory bowel disease.

Purpose: We report a male child who presented at 15 months with perianal abscesses and proctitis, progressing to transmural pancolitis with colocutaneous fistulae, consistent with a Crohn disease-like illness. The age and severity of the presentation suggested an underlying immune defect; however, despite comprehensive clinical evaluation, we were unable to arrive at a definitive diagnosis, thereby restricting clinical management.

Methods: We sought to identify the causative mutation(s) through exome sequencing to provide the necessary additional information required for clinical management.

Dynamic Lkb1-TORC1 signaling as a possible mechanism for regulating the endoderm-intestine transition.

The intestinal epithelium arises from undifferentiated endoderm via a developmental program known as the endoderm-intestine transition (EIT). Previously we found that the target of rapamycin complex 1 (TORC1) regulates intestinal growth and differentiation during the EIT in zebrafish. Here we address a possible role for the tumor-suppressor kinase Lkb1 in regulating TORC1 in this context.

The protective role of intestinal alkaline phosphatase in necrotizing enterocolitis.

Background: Enterocytes produce intestinal alkaline phosphatase (iAP), which detoxifies lipopolysaccharide (LPS), a mediator in necrotizing enterocolitis (NEC) pathogenesis. We hypothesize that aberrant expression or function of iAP contributes to the pathogenesis of NEC.

Materials And Methods: Newborn Sprague Dawley rat pups were divided into three main groups.

PhotoMorphs: a novel light-activated reagent for controlling gene expression in zebrafish.

Manipulating gene expression in zebrafish is critical for exploiting the full potential of this vertebrate model organism. Morpholino oligos are the most commonly used antisense technology for knocking down gene expression. However, morpholinos suffer from a lack of control over the timing and location of knockdown.

RBM19 is essential for preimplantation development in the mouse.

Background: RNA-binding motif protein 19 (RBM19, NCBI Accession # NP_083038) is a conserved nucleolar protein containing 6 conserved RNA recognition motifs. Its biochemical function is to process rRNA for ribosome biogenesis, and it has been shown to play a role in digestive organ development in zebrafish. Here we analyzed the role of RBM19 during mouse embryonic development by generating mice containing a mutation in the Rbm19 locus via gene-trap insertion.

A whole-animal microplate assay for metabolic rate using zebrafish.

Regulation of whole-body metabolism and energy homeostasis has been shown to require signaling between multiple organs. To identify genetic programs that determine metabolic rate, and compounds that can modify it, a whole-animal assay amenable to large-scale screening was developed. The direct correlation of acid production with metabolic rate was exploited to use a noninvasive colorimetric assay for acid secretion by individual zebrafish larvae in a 96-well plate format.

A zebrafish model for the Shwachman-Diamond syndrome (SDS).

The Shwachman-Diamond syndrome (SDS) is characterized by exocrine pancreatic insufficiency, neutrophil defect, and skeletal abnormalities. The molecular basis for this syndrome was recently identified as a defect in a novel nucleolar protein termed the Shwachman-Bodian-Diamond syndrome (SBDS) protein. Beyond human pathologic descriptions, there are little data addressing the role of SBDS during pancreas and granulocytes development.

Zebrafish Offers New Perspective on Developmental Role of TOR Signaling.

Genetic studies on the molecular basis of growth control have converged on the target of rapamycin (TOR) pathway as a key regulator.1 When stimulated by nutrients (i.e.

Target of rapamycin (TOR) signaling controls epithelial morphogenesis in the vertebrate intestine.

The target of rapamycin (TOR) signaling pathway regulates cell growth and proliferation, however the extent to which TOR signaling mediates particular organogenesis programs remains to be determined. Here we report an examination of TOR signaling during zebrafish development, using a combination of small molecule treatment and morpholino-mediated gene knockdown. First, we amplified and sequenced the full-length cDNA for the zebrafish TOR ortholog (ztor).

Rbm19 is a nucleolar protein expressed in crypt/progenitor cells of the intestinal epithelium.

Intestinal development and homeostasis rely on the coordination of proliferation and differentiation of the epithelium. To better understand this process, we are studying Rbm19, a gene expressed in the gut epithelium that is essential for intestinal morphogenesis and differentiation in the zebrafish (Development 130, 3917). Here we analyzed the expression of Rbm19 in several biological contexts that feature proliferation/differentiation cell fate decisions.

Nil per os encodes a conserved RNA recognition motif protein required for morphogenesis and cytodifferentiation of digestive organs in zebrafish.

Digestive organ development occurs through a sequence of morphologically distinct stages, from overtly featureless endoderm, through organ primordia to, ultimately, adult form. The developmental controls that govern progression from one stage to the next are not well understood. To identify genes required for the formation of vertebrate digestive organs we performed a genetic screen in zebrafish.