The identification of protein and RNA interactors of the splicing factor Caper in the adult nervous system.

Post-transcriptional gene regulation is a fundamental mechanism that helps regulate the development and healthy aging of the nervous system. Mutations that disrupt the function of RNA-binding proteins (RBPs), which regulate post-transcriptional gene regulation, have increasingly been implicated in neurological disorders including amyotrophic lateral sclerosis, Fragile X Syndrome, and spinal muscular atrophy. Interestingly, although the majority of RBPs are expressed widely within diverse tissue types, the nervous system is often particularly sensitive to their dysfunction.

Roles for the RNA-Binding Protein Caper in Reproductive Output in .

RNA binding proteins (RBPs) play a fundamental role in the post-transcriptional regulation of gene expression within the germline and nervous system. This is underscored by the prevalence of mutations within RBP-encoding genes being implicated in infertility and neurological disease. We previously described roles for the highly conserved RBP Caper in neurite morphogenesis in the larval peripheral system and in locomotor behavior.

Exploring the Diverse Functional and Regulatory Consequences of Alternative Splicing in Development and Disease.

Alternative splicing is a fundamental mechanism of eukaryotic RNA regulation that increases the transcriptomic and proteomic complexity within an organism. Moreover, alternative splicing provides a framework for generating unique yet complex tissue- and cell type-specific gene expression profiles, despite using a limited number of genes. Recent efforts to understand the negative consequences of aberrant splicing have increased our understanding of developmental and neurodegenerative diseases such as spinal muscular atrophy, frontotemporal dementia and Parkinsonism linked to chromosome 17, myotonic dystrophy, and amyotrophic lateral sclerosis.

CPB-3 and CGH-1 localize to motile particles within dendrites in C. elegans PVD sensory neurons.

Objective: RNA-binding proteins (RBPs) are important regulators of gene expression that influence mRNA splicing, stability, localization, transport, and translational control. In particular, RBPs play an important role in neurons, which have a complex morphology. Previously, we showed that there are many RBPs that play a conserved role in dendrite development in Drosophila dendritic arborization neurons and Caenorhabditis elegans (C.

The conserved alternative splicing factor caper regulates neuromuscular phenotypes during development and aging.

RNA-binding proteins play an important role in the regulation of post-transcriptional gene expression throughout the nervous system. This is underscored by the prevalence of mutations in genes encoding RNA splicing factors and other RNA-binding proteins in a number of neurodegenerative and neurodevelopmental disorders. The highly conserved alternative splicing factor Caper is widely expressed throughout the developing embryo and functions in the development of various sensory neural subtypes in the Drosophila peripheral nervous system.

The cytoplasmic polyadenylation element binding protein (CPEB), Orb, is important for dendrite development and neuron fate specification in Drosophila melanogaster.

Cytoplasmic polyadenylation element binding proteins (CPEBs) are widely conserved proteins that regulate the length of poly(A) tails in the cytoplasm, regulate translation, and regulate mRNA transport. While CPEBs are best known for regulating maternal messages in oocytes, CPEBs also have roles in many other cell types including neurons. Here we extend our knowledge of the roles of CPEBs in neurons by showing that the Drosophila CPEB-encoding gene, orb, is required for proper dendrite development in larval sensory dendritic arborization neurons.

Shep interacts with posttranscriptional regulators to control dendrite morphogenesis in sensory neurons.

RNA binding proteins (RBPs) mediate posttranscriptional gene regulatory events throughout development. During neurogenesis, many RBPs are required for proper dendrite morphogenesis within Drosophila sensory neurons. Despite their fundamental role in neuronal morphogenesis, little is known about the molecular mechanisms in which most RBPs participate during neurogenesis.

as a Model for Assessing the Function of RNA-Binding Proteins during Neurogenesis and Neurological Disease.

An outstanding question in developmental neurobiology is how RNA processing events contribute to the regulation of neurogenesis. RNA processing events are increasingly recognized as playing fundamental roles in regulating multiple developmental events during neurogenesis, from the asymmetric divisions of neural stem cells, to the generation of complex and diverse neurite morphologies. Indeed, both asymmetric cell division and neurite morphogenesis are often achieved by mechanisms that generate asymmetric protein distributions, including post-transcriptional gene regulatory mechanisms such as the transport of translationally silent messenger RNAs (mRNAs) and local translation of mRNAs within neurites.

The RNA-binding protein caper is required for sensory neuron development in Drosophila melanogaster.

Background: Alternative splicing mediated by RNA-binding proteins (RBPs) is emerging as a fundamental mechanism for the regulation of gene expression. Alternative splicing has been shown to be a widespread phenomenon that facilitates the diversification of gene products in a tissue-specific manner. Although defects in alternative splicing are rooted in many neurological disorders, only a small fraction of splicing factors have been investigated in detail.

Drosophila Shep and C. elegans SUP-26 are RNA-binding proteins that play diverse roles in nervous system development.

The Caenorhabditis elegans gene sup-26 encodes a well-conserved RNA-recognition motif-containing RNA-binding protein (RBP) that functions in dendrite morphogenesis of the PVD sensory neuron. The Drosophila ortholog of sup-26, alan shepard (shep), is expressed throughout the nervous system and has been shown to regulate neuronal remodeling during metamorphosis. Here, we extend these studies to show that sup-26 and shep are required for the development of diverse cell types within the nematode and fly nervous systems during embryonic and larval stages.

Connecting genotypes, phenotypes and fitness: harnessing the power of CRISPR/Cas9 genome editing.

One of the fundamental goals in evolution and ecology is to identify the genetic basis of adaptive phenotypes. Unfortunately, progress towards this goal has been hampered by a lack of genetic tools available for nonmodel organisms. The exciting new development of the CRISPR (clustered regularly interspaced short palindromic repeat)/Cas9 (CRISPR-associated nuclease 9) genome-editing system now promises to transform the field of molecular ecology by providing a versatile toolkit for manipulating the genome of a wide variety of organisms.

Conserved RNA-binding proteins required for dendrite morphogenesis in Caenorhabditis elegans sensory neurons.

The regulation of dendritic branching is critical for sensory reception, cell-cell communication within the nervous system, learning, memory, and behavior. Defects in dendrite morphology are associated with several neurologic disorders; thus, an understanding of the molecular mechanisms that govern dendrite morphogenesis is important. Recent investigations of dendrite morphogenesis have highlighted the importance of gene regulation at the posttranscriptional level.

Extensive use of RNA-binding proteins in Drosophila sensory neuron dendrite morphogenesis.

The large number of RNA-binding proteins and translation factors encoded in the Drosophila and other metazoan genomes predicts widespread use of post-transcriptional regulation in cellular and developmental processes. Previous studies identified roles for several RNA-binding proteins in dendrite branching morphogenesis of Drosophila larval sensory neurons. To determine the larger contribution of post-transcriptional gene regulation to neuronal morphogenesis, we conducted an RNA interference screen to identify additional Drosophila proteins annotated as either RNA-binding proteins or translation factors that function in producing the complex dendritic trees of larval class IV dendritic arborization neurons.

Regional modulation of a stochastically expressed factor determines photoreceptor subtypes in the Drosophila retina.

Stochastic mechanisms are sometimes utilized to diversify cell fates, especially in nervous systems. In the Drosophila retina, stochastic expression of the PAS-bHLH transcription factor Spineless (Ss) controls photoreceptor subtype choice. In one randomly distributed subset of R7 photoreceptors, Ss activates Rhodopsin4 (Rh4) and represses Rhodopsin3 (Rh3); counterparts lacking Ss express Rh3 and repress Rh4.

Combinatorial use of translational co-factors for cell type-specific regulation during neuronal morphogenesis in Drosophila.

The translational regulators Nanos (Nos) and Pumilio (Pum) work together to regulate the morphogenesis of dendritic arborization (da) neurons of the Drosophila larval peripheral nervous system. In contrast, Nos and Pum function in opposition to one another in the neuromuscular junction to regulate the morphogenesis and the electrophysiological properties of synaptic boutons. Neither the cellular functions of Nos and Pum nor their regulatory targets in neuronal morphogenesis are known.

prdm1a Regulates sox10 and islet1 in the development of neural crest and Rohon-Beard sensory neurons.

The PR domain containing 1a, with ZNF domain factor, gene (prdm1a) plays an integral role in the development of a number of different cell types during vertebrate embryogenesis, including neural crest cells, Rohon-Beard (RB) sensory neurons and the cranial neural crest-derived craniofacial skeletal elements. To better understand how Prdm1a regulates the development of various cell types in zebrafish, we performed a microarray analysis comparing wild type and prdm1a mutant embryos and identified a number of genes with altered expression in the absence of prdm1a. Rescue analysis determined that two of these, sox10 and islet1, lie downstream of Prdm1a in the development of neural crest cells and RB neurons, respectively.

Distinct mechanisms for mRNA localization during embryonic axis specification in the wasp Nasonia.

mRNA localization is a powerful mechanism for targeting factors to different regions of the cell and is used in Drosophila to pattern the early embryo. During oogenesis of the wasp Nasonia, mRNA localization is used extensively to replace the function of the Drosophila bicoid gene for the initiation of patterning along the antero-posterior axis. Nasonia localizes both caudal and nanos to the posterior pole, whereas giant mRNA is localized to the anterior pole of the oocyte; orthodenticle1 (otd1) is localized to both the anterior and posterior poles.

A caudal mRNA gradient controls posterior development in the wasp Nasonia.

One of the earliest steps of embryonic development is the establishment of polarity along the anteroposterior axis. Extensive studies of Drosophila embryonic development have elucidated mechanisms for establishing polarity, while studies with other model systems have found that many of these molecular components are conserved through evolution. One exception is Bicoid, the master organizer of anterior development in Drosophila and higher dipterans, which is not conserved.

Regulation and function of tailless in the long germ wasp Nasonia vitripennis.

In the long germ insect Drosophila, the gene tailless acts to pattern the terminal regions of the embryo. Loss of function of this gene results in the deletion of the anterior and posterior terminal structures and the eighth abdominal segment. Drosophila tailless is activated by the maternal terminal system through Torso signaling at both poles of the embryo, with additional activation by Bicoid at the anterior.

Transcription and DNA adducts: what happens when the message gets cut off?

DNA damage located within a gene's transcription unit can cause RNA polymerase to stall at the modified site, resulting in a truncated transcript, or progress past, producing full-length RNA. However, it is not immediately apparent why some lesions pose strong barriers to elongation while others do not. Studies using site-specifically damaged DNA templates have demonstrated that a wide range of lesions can impede the progress of elongating transcription complexes.