Huntingtin Plays a Role in the Physiological Response to Ethanol in Drosophila.

Background: Huntingtin (htt) protein is an essential regulator of nervous system function through its various neuroprotective and pro-survival functions, and loss of wild-type htt function is implicated in the etiology of Huntington's disease. While its pathological role is typically understood as a toxic gain-of-function, some neuronal phenotypes also result from htt loss. Therefore, it is important to understand possible roles for htt in other physiological circumstances.

Correction: Dilp-2-mediated PI3-kinase activation coordinates reactivation of quiescent neuroblasts with growth of their glial stem cell niche.

[This corrects the article DOI: 10.1371/journal.pbio.

Dilp-2-mediated PI3-kinase activation coordinates reactivation of quiescent neuroblasts with growth of their glial stem cell niche.

Dietary nutrients provide macromolecules necessary for organism growth and development. In response to animal feeding, evolutionarily conserved growth signaling pathways are activated, leading to increased rates of cell proliferation and tissue growth. It remains unclear how different cell types within developing tissues coordinate growth in response to dietary nutrients and whether coordinated growth of different cell types is necessary for proper tissue function.

Eyeless uncouples mushroom body neuroblast proliferation from dietary amino acids in .

Cell proliferation is coupled with nutrient availability. If nutrients become limited, proliferation ceases, because growth factor and/or PI3-kinase activity levels become attenuated. Here, we report an exception to this generality within a subpopulation of neural stem cells (neuroblasts).

Developmental regulation of planar cell polarity and hair-bundle morphogenesis in auditory hair cells: lessons from human and mouse genetics.

Hearing loss is the most common and costly sensory defect in humans and genetic causes underlie a significant proportion of affected individuals. In mammals, sound is detected by hair cells (HCs) housed in the cochlea of the inner ear, whose function depends on a highly specialized mechanotransduction organelle, the hair bundle. Understanding the factors that regulate the development and functional maturation of the hair bundle is crucial for understanding the pathophysiology of human deafness.

Lis1 mediates planar polarity of auditory hair cells through regulation of microtubule organization.

The V-shaped hair bundles atop auditory hair cells and their uniform orientation are manifestations of epithelial planar cell polarity (PCP) required for proper perception of sound. PCP is regulated at the tissue level by a conserved core Wnt/PCP pathway. However, the hair cell-intrinsic polarity machinery is poorly understood.

PTK7 regulates myosin II activity to orient planar polarity in the mammalian auditory epithelium.

Background: Planar cell polarity (PCP) signaling is a key regulator of epithelial morphogenesis, including neural tube closure and the orientation of inner ear sensory hair cells, and is mediated by a conserved noncanonical Wnt pathway. Ptk7 is a novel vertebrate-specific regulator of PCP, yet the mechanisms by which Ptk7 regulates mammalian epithelial PCP remain poorly understood.

Results: Here we show that, in the mammalian auditory epithelium, Ptk7 is not required for membrane recruitment of Dishevelled 2; Ptk7 and Frizzled3/Frizzled6 receptors act in parallel and have opposing effects on hair cell PCP.

Redundant functions of Rac GTPases in inner ear morphogenesis.

Development of the mammalian inner ear requires coordination of cell proliferation, cell fate determination and morphogenetic movements. While significant progress has been made in identifying developmental signals required for inner ear formation, less is known about how distinct signals are coordinated by their downstream mediators. Members of the Rac family of small GTPases are known regulators of cytoskeletal remodeling and numerous other cellular processes.

Kif3a regulates planar polarization of auditory hair cells through both ciliary and non-ciliary mechanisms.

Auditory hair cells represent one of the most prominent examples of epithelial planar polarity. In the auditory sensory epithelium, planar polarity of individual hair cells is defined by their V-shaped hair bundle, the mechanotransduction organelle located on the apical surface. At the tissue level, all hair cells display uniform planar polarity across the epithelium.

The small GTPase Rac1 regulates auditory hair cell morphogenesis.

Morphogenesis of sensory hair cells, in particular their mechanotransduction organelle, the stereociliary bundle, requires highly organized remodeling of the actin cytoskeleton. The roles of Rho family small GTPases during this process remain unknown. Here we show that deletion of Rac1 in the otic epithelium resulted in severe defects in cochlear epithelial morphogenesis.

In silico gene selection for custom oligonucleotide microarray design.

A method for systematically selecting the large number of sequences needed to custom design an oligonucleotide microarray was presented. This approach uses a Perl script to query sequence databases with gene lists obtained from previously designed (and publicly available) microarrays. Homologous sequences passing a user-defined threshold are returned and stored in a candidate gene database.

The use of microarray technology in nonmammalian vertebrate systems.

Among vertebrates, the mammalian systems that are frequently used to investigate questions related to human health have gained the most benefit from microarray technology to date. However, it is clear that biological investigations and the generalized conclusions drawn from them, can only be enhanced by including organisms in which specific processes can be readily studied because of their genetic, physiological, or developmental disposition. As a result, the field of functional genomics has recently begun to embrace a number of other vertebrate species.

The role of early lineage in GABAergic and glutamatergic cell fate determination in Xenopus laevis.

Proper functioning of the adult nervous system is critically dependent on neurons adopting the correct neurotransmitter phenotype during early development. Whereas the importance of cell-cell communication in fate determination is well documented for a number of neurotransmitter phenotypes, the contributions made by early lineage to this process remain less clear. This is particularly true for gamma-aminobutyric acid (GABA)ergic and glutamatergic neurons, which are present as the most abundant inhibitory and excitatory neurons, respectively, in the central nervous system of all vertebrates.

In silico gene selection strategy for custom microarray design.

Microarray technology has become an important tool for studying large-scale gene expression for a diversity of biological applications. However, there are a number of experimental settings for which commercial arrays are either unsuitable or unavailable despite the existence of sequence information. With the increasing availability of custom array manufacturing services, it is now feasible to design high-density arrays for any organism having sequence data.

Mechanisms regulating the origins of the vertebrate vascular system.

In order to sustain growth, differentiation, and organogenesis, vertebrate embryos must form a functional vascular system early in embryonic development. Intrinsic interest in this process as well as the promise of potential clinical applications has led to significant progress in understanding the mechanisms governing the formation of the vascular system, however the earliest stages of vascular development--the emergence of committed endothelial precursors from the mesoderm--remain unclear. A review of the current literature reveals an unexpected diversity and heterogeneity with respect to where vascular endothelial cells originate in the embryo, when they become committed and the mechanisms governing how endothelial cells acquire their identity.

Short upstream region drives dynamic expression of hypoxia-inducible factor 1alpha during Xenopus development.

Hypoxia-inducible factor 1alpha (HIF-1alpha) plays a central role in regulating oxygen-dependent gene expression and is involved in a range of pathways implicated in cellular survival, proliferation, and development. While the posttranslational regulation of HIF-1alpha is well characterized, the relative importance of its control at the transcriptional level during development remains less clear. Although the mouse and human promoter regions have been analyzed in vitro, to date, there has been no in vivo analysis of any vertebrate HIF-1alpha promoter.