Actionable Data from Iterative Cognitive Walkthroughs: Creating the Research Roadmap Website as an Interactive Guide to Facilitate Research.

The goal of this project was to assess usability and acceptance of a web-based tool after iterative development based on cognitive walkthroughs. The website is a "Research Roadmap", modeled after the NYC Subway map, and designed to help the user navigate the complex structure of research at a large multi-institution organization. A mixed process of evaluation and design was applied; after an initial survey phase, the website was revised, then another cycle of feedback was implemented.

Promoter-enhancer looping and shadow enhancers of the mouse αA-crystallin locus.

Gene regulation by enhancers is important for precise temporal and spatial gene expression. Enhancers can drive gene expression regardless of their location, orientation or distance from the promoter. Changes in chromatin conformation and chromatin looping occur to bring the promoter and enhancers into close proximity.

Identification and characterization of FGF2-dependent mRNA: microRNA networks during lens fiber cell differentiation.

MicroRNAs (miRNAs) and fibroblast growth factor (FGF) signaling regulate a wide range of cellular functions, including cell specification, proliferation, migration, differentiation, and survival. In lens, both these systems control lens fiber cell differentiation; however, a possible link between these processes remains to be examined. Herein, the functional requirement for miRNAs in differentiating lens fiber cells was demonstrated via conditional inactivation of Dicer1 in mouse (Mus musculus) lens.

Histone posttranslational modifications and cell fate determination: lens induction requires the lysine acetyltransferases CBP and p300.

Lens induction is a classical embryologic model to study cell fate determination. It has been proposed earlier that specific changes in core histone modifications accompany the process of cell fate specification and determination. The lysine acetyltransferases CBP and p300 function as principal enzymes that modify core histones to facilitate specific gene expression.

Pax6 interactions with chromatin and identification of its novel direct target genes in lens and forebrain.

Pax6 encodes a specific DNA-binding transcription factor that regulates the development of multiple organs, including the eye, brain and pancreas. Previous studies have shown that Pax6 regulates the entire process of ocular lens development. In the developing forebrain, Pax6 is expressed in ventricular zone precursor cells and in specific populations of neurons; absence of Pax6 results in disrupted cell proliferation and cell fate specification in telencephalon.

Chromatin remodeling enzyme Brg1 is required for mouse lens fiber cell terminal differentiation and its denucleation.

Background: Brahma-related gene 1 (Brg1, also known as Smarca4 and Snf2β) encodes an adenosine-5'-triphosphate (ATP)-dependent catalytical subunit of the (switch/sucrose nonfermentable) (SWI/SNF) chromatin remodeling complexes. SWI/SNF complexes are recruited to chromatin through multiple mechanisms, including specific DNA-binding factors (for example, heat shock transcription factor 4 (Hsf4) and paired box gene 6 (Pax6)), chromatin structural proteins (for example, high-mobility group A1 (HMGA1)) and/or acetylated core histones. Previous studies have shown that a single amino acid substitution (K798R) in the Brg1 ATPase domain acts via a dominant-negative (dn) mechanism.

Identification of pax6-dependent gene regulatory networks in the mouse lens.

Lineage-specific DNA-binding transcription factors regulate development by activating and repressing particular set of genes required for the acquisition of a specific cell type. Pax6 is a paired domain and homeodomain-containing transcription factor essential for development of central nervous, olfactory and visual systems, as well as endocrine pancreas. Haploinsufficiency of Pax6 results in perturbed lens development and homeostasis.

Transcriptional regulation of mouse alpha A-crystallin gene in a 148kb Cryaa BAC and its derivates.

Background: alphaA-crystallin is highly expressed in the embryonic, neonatal and adult mouse lens. Previously, we identified two novel distal control regions, DCR1 and DCR3. DCR1 was required for transgenic expression of enhanced green fluorescent protein, EGFP, in lens epithelium, whereas DCR3 was active during "late" stages of lens primary fiber cell differentiation.

Rybp, a polycomb complex-associated protein, is required for mouse eye development.

Background: Rybp (Ring1 and YY1 binding protein) is a zinc finger protein which interacts with the members of the mammalian polycomb complexes. Previously we have shown that Rybp is critical for early embryogenesis and that haploinsufficiency of Rybp in a subset of embryos causes failure of neural tube closure. Here we investigated the requirement for Rybp in ocular development using four in vivo mouse models which resulted in either the ablation or overexpression of Rybp.

Distinct embryonic expression and localization of CBP and p300 histone acetyltransferases at the mouse alphaA-crystallin locus in lens.

Mouse alphaA-crystallin gene encodes the most abundant protein of the mammalian lens. Expression of alphaA-crystallin is regulated temporally and spatially during lens development with initial expression in the lens vesicle followed by strong upregulation in the differentiating primary lens fibers. Lens-specific expression of alphaA-crystallin is mediated by DNA-binding transcription factors Pax6, c-Maf and CREB bound to its promoter region.

Palm is expressed in both developing and adult mouse lens and retina.

Background: Paralemmin (Palm) is a prenyl-palmitoyl anchored membrane protein that can drive membrane and process formation in neurons. Earlier studies have shown brain preferred Palm expression, although this protein is a major water insoluble protein in chicken lens fiber cells and the Palm gene may be regulated by Pax6.

Methods: The expression profile of Palm protein in the embryonic, newborn and adult mouse eye as well as dissociated retinal neurons was determined by confocal immunofluorescence.