Barr MM (2003) Physiol Genomics "Super models."

Barr MM

[Physiol Genomics, 2003]

Model organisms have been used over a century to understand basic, conserved biological processes. The study of these experimental systems began with genetics and development, moved into molecular and cellular biology, and most recently propelled into functional genomics and proteomics. The goal of this review is simple: to discuss the place of model organisms in "The Age of the Ome": the genome, the transcriptome, and the proteome. This review will address the following questions. What exactly is a model organism? What characteristics make an excellent model system? Using the yeast Saccharomyces cerevisiae and the nematode Caenorhabditis elegans as examples, this review will discuss these issues with the aim of demonstrating how model organisms remain indispensable scientific tools for understanding complex biological pathways and human

Maureen M. Barr (2006) WormBook "Male mating behavior."

Maureen M. Barr

[WormBook, 2006]

Caenorhabditis elegans male mating provides an excellent opportunity to determine how sensory perception regulates behavior and motor programs. The male-specific nervous system and muscles are superimposed over the general nervous system and musculature. Genetic screens and genomic approaches have identified male-specific and male-enriched genes as well as non-sex specific molecules specialized for mating sub-behaviors. In this chapter, we discuss the cellular, genetic, and molecular basis for male mating behavior.

Maureen M Barr (2001) International C. elegans Meeting "Lov neurotransmission"

Maureen M Barr

[International C. elegans Meeting, 2001]

The nervous system of the adult C. elegans male possesses 381 neurons to the hermaphrodite's 302. These additional sex-specific neurons are required for male mating behaviors, namely, response to hermaphrodite contact, backing, turning, location of vulva (Lov), spicule insertion, and sperm transfer. We are specifically studying Lov behavior at the cellular, genetic, and molecular levels. The HOA and HOB hook neurons are required for Lov behavior (1) and the putative sensory receptor lov-1 is expressed in HOB (2). How does signaling initiated by the LOV-1 receptor culminate in Lov behavior? We are interested in identifying the neurotransmitters and neuropeptides used by the HOA and HOB mechano- and chemosensory neurons, respectively (3). Anne Hart and Arif Nathoo have identified 21 putative n europeptide like protein ( nlp ) genes in C. elegans and made transcriptional GFP fusions (4) which we have screened for expression in the adult male tail. An nlp-8::gfp transcriptional fusion is expressed uniformly throughout the HOB neuron. Expression is also observed in other non-sex, non-stage specific cells. We have constructed a full length nlp-8::gfp translational fusion and observed expression only in HOB, suggesting nlp-8 may be a Lov neuropeptide. We are exploring the role of nlp-8 in Lov behavior using genetic and molecular approaches. Liu, K. S. and P. W. Sternberg. 1995. Neuron 14:79-89. Barr, M. M. and P. W. Sternberg. 1999. Nature 401: 386-389. Sulston, J. E. et al. 1980. Developmental Biology 78:542-576. Nathoo, A., R. Moeller, and A. Hart. 1999. International Worm Meeting abstract 621.

Barr MM (2016) PLoS Genet "Middle Age Has Its Advantages."

Barr MM

[PLoS Genet, 2016]

Barr MM et al. (1997) International C. elegans Meeting "HERMAPHRODITE SIGNALS FOR MALE MATING"

Liu KK, Sternberg PW, Barr MM

[International C. elegans Meeting, 1997]

Although the hermaphrodite is a behaviorally passive mating partner, her vulva and uterus provide cues to the male. The vulva may signal the male hook sensillum, causing the male to stop backing and to attempt spicule insertion. The uterus may signal male sperm release. We are interested in the cellular basis of both hermaphrodite cues and male responses. To elucidate the nature of vulva and uterine cues, intact or neuron-ablated males were paired with ablated or mutant hermaphrodites. We found that the secondary vulva cells are both necessary and sufficient for vulva location. The male hook and post-cloacal sensilla may be involved in sensing and discriminating secondary cell characteristics. Males can transfer sperm to hermaphrodites with a defective vulval-uterine connection, suggesting the uterine signal may be diffusible. SPV-ablated males can transfer sperm to uterine-ablated hermaphrodites, supporting a role for SPV as a negative regulator of sperm transfer and sensor of an inhibitory uterine signal. We are now carrying out more refined ablation studies and behavioral analysis to limit these hermaphrodite cues to a single cell or minimal group of cells. We hope to determine whether chemosensation, mechanosensation, or both are involved in male behavioral responses.

Barr MM (2014) Semin Cell Dev Biol "C. elegans male mating behavior. Introduction."

Barr MM

[Semin Cell Dev Biol, 2014]

Barr MM et al. (1996) West Coast Worm Meeting "VULVA LOCATION: HOW A MALE GETS TO WHERE HE'S GOING"

Sternberg PW, Hajdu-Cronin YM, Liu KK, Barr MM

[West Coast Worm Meeting, 1996]

C. elegans male mating behavior involves multiple steps, including response to the hermaphrodite, backing along her body, turning via a deep ventral bend at the end of her body, vulva location, spicule insertion, and sperm transfer. The male must integrate multiple signals and behave according to the movements of the disinterested, otherwise self-fertilizing hermaphrodite. Vulva location requires input from three sensilla: the hook, the post-cloacal sensilla (p.c.s.), and the spicules (1). The step of vulva location is complex: neuronal circuitry is partially redundant and this functional overlap allows for behavioral adaptation. Vulva location behavior is an excellent model system to dissect neuronal redundancy and behavioral plasticity. By screening for copulation defective (Cod) mutants, several vulva location mutants have been isolated. However, none exhibit severe behavioral or mating efficiency defects. As different sensory pathways appear to be affected in cod-13(sy420)III and cod-12(sy419)II, we are analyzing these mutants at genetic and cellular (via laser ablations) levels. sy420 most closely resembles hook-ablation (passes the vulva frequently) while sy419 mimics p.c.s.-ablation (locates but easily loses the vulva). sy420 maps to the interval defined by dpy-17 lon-1. Hook-ablated sy419 males behave distinctly from hook-ablated wild-type males. Hook-minus wild-type males pass the vulva and circle the hermaphrodite for several minutes before initiating a slow search that requires the p.c.s. and spicules (1). Hookless sy419 males exhibit a constitutive vulva location behavior involving spicule protraction at random positions along the hermaphrodite's body often coupled with premature sperm release. These behaviors in sy419 are vulva-dependent but uterus-independent, suggesting a possible defect in sensory feedback regulation. Combination ablations are being performed to determine which neurons are required for this aberrant behavior. Vulva location Cod mutants may affect partially redundant genes and a synergistic Cod phenotype may be produced by two mutations. Since hook ablation augments the behavioral defects of a sy419 male, sy419 may provide a sensitive background to obtain mutants with hook-like defects. (1) Neuron (1995) 4: 79-89.

Barr MM et al. (2000) Midwest Worm Meeting "Polycystic Kidney Disease (PKD) gene homologs and male mating behavior"

Barr MM, Sternberg PW

[Midwest Worm Meeting, 2000]

We have identified two genes, lov-1 and pkd-2, that are required for the male sensory behaviors of response and vulva location (1). lov-1 and pkd-2 encode PKD1 and PKD2 homologues, respectively. Autosomal Dominant Polycystic Kidney Disease affects 1 in 1,000 individuals and mutation in either the PKD1 or PKD2 gene accounts for 95% of all cases. Hence, we are using the lov-1 and pkd-2 pathway(s) to study the cell and molecular biology of PKD. lov-1::gfp and pkd-2::gfp are coexpressed and colocalized in the male sensory neurons of the rays, hook, and head. The male sensory neurons of lov-1 and pkd-2 mutants appear wild type. Combined, these observations suggest several possible functions for the polycystins in male mating behavior. lov-1 and pkd-2 may potentially function in sensory signal transduction, as molecular scaffolds, in the establishment and/or maintenance of neuronal cell polarity, or developmentally in the ultrastructural assembly of male-specific cilia. To test the hypothesis that lov-1 and pkd-2 act in concert, genetic interactions between lov-1 and pkd-2 are being examined. Additionally, other components that may be involved in the LOV-1/PKD-2 polycystin pathway are being characterized. For example, Tg737, the mouse Autosomal Recessive Polycystic Kidney Disease gene, encodes a protein that interacts with polycystin 1. Interestingly, the domain of interaction is conserved between LOV-1 and PKD1 (1). We have identified a Tg737 homolog in the C. elegans genome database and are analyzing its role in sensory behaviors. (1) Barr MM, Sternberg PW. Nature. 1999 Sep 23;401(6751):386-9.

Barr MM (2005) J Am Soc Nephrol "Caenorhabditis elegans as a model to study renal development and disease: sexy cilia."

Barr MM

[J Am Soc Nephrol, 2005]

The nematode Caenorhabditis elegans has no kidney per se, yet "the worm" has proved to be an excellent model to study renal-related issues, including tubulogenesis of the excretory canal, membrane transport and ion channel function, and human genetic diseases including autosomal dominant polycystic kidney disease (ADPKD). The goal of this review is to explain how C. elegans has provided insight into cilia development, cilia function, and human cystic kidney diseases.

Barr MM et al. (2018) Genetics "Sexual Dimorphism and Sex Differences inCaenorhabditis elegansNeuronal Development and Behavior."

Barr MM, Portman DS, Garcia LR

[Genetics, 2018]

As fundamental features of nearly all animal species, sexual dimorphisms and sex differences have particular relevance for the development and function of the nervous system. The unique advantages of the nematode<i>Caenorhabditis elegans</i>have allowed the neurobiology of sex to be studied at unprecedented scale, linking ultrastructure, molecular genetics, cell biology, development, neural circuit function, and behavior. Sex differences in the<i>C</i><i>. elegans</i>nervous system encompass prominent anatomical dimorphisms as well as differences in physiology and connectivity. The influence of sex on behavior is just as diverse, with biological sex programming innate sex-specific behaviors and modifying many other aspects of neural circuit function. The study of these differences has provided important insights into mechanisms of neurogenesis, cell fate specification, and differentiation; synaptogenesis and connectivity; principles of circuit function, plasticity, and behavior; social communication; and many other areas of modern neurobiology.