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190 Publications

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    07/01/12 | Dorsorostral snout muscles in the rat subserve coordinated movement for whisking and sniffing.
    Haidarliu S, Golomb D, Kleinfeld D, Ahissar E
    Anatomical Record. 2012 Jul;295(7):1181-91. doi: 10.1002/ar.22501

    Histochemical examination of the dorsorostral quadrant of the rat snout revealed superficial and deep muscles that are involved in whisking, sniffing, and airflow control. The part of M. nasolabialis profundus that acts as an intrinsic (follicular) muscle to facilitate protraction and translation of the vibrissae is described. An intraturbinate and selected rostral-most nasal muscles that can influence major routs of inspiratory airflow and rhinarial touch through their control of nostril configuration, atrioturbinate and rhinarium position, were revealed.

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    Baker Lab
    01/01/12 | Doublesex functions early and late in gustatory sense organ development.
    Mellert DJ, Robinett CC, Baker BS
    PLoS One. 2012;7:e51489. doi: 10.1371/journal.pone.0051489

    Somatic sexual dimorphisms outside of the nervous system in Drosophila melanogaster are largely controlled by the male- and female-specific Doublesex transcription factors (DSX(M) and DSX(F), respectively). The DSX proteins must act at the right times and places in development to regulate the diverse array of genes that sculpt male and female characteristics across a variety of tissues. To explore how cellular and developmental contexts integrate with doublesex (dsx) gene function, we focused on the sexually dimorphic number of gustatory sense organs (GSOs) in the foreleg. We show that DSX(M) and DSX(F) promote and repress GSO formation, respectively, and that their relative contribution to this dimorphism varies along the proximodistal axis of the foreleg. Our results suggest that the DSX proteins impact specification of the gustatory sensory organ precursors (SOPs). DSX(F) then acts later in the foreleg to regulate gustatory receptor neuron axon guidance. These results suggest that the foreleg provides a unique opportunity for examining the context-dependent functions of DSX.

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    10/18/12 | Drosophila CPEB Orb2A mediates memory independent of Its RNA-binding domain.
    Krüttner S, Stepien B, Noordermeer JN, Mommaas MA, Mechtler K, Dickson BJ, Keleman K
    Neuron. 2012 Oct 18;76(2):383-95. doi: 10.1016/j.neuron.2012.08.028

    Long-term memory and synaptic plasticity are thought to require the synthesis of new proteins at activated synapses. The CPEB family of RNA binding proteins, including Drosophila Orb2, has been implicated in this process. The precise mechanism by which these molecules regulate memory formation is however poorly understood. We used gene targeting and site-specific transgenesis to specifically modify the endogenous orb2 gene in order to investigate its role in long-term memory formation. We show that the Orb2A and Orb2B isoforms, while both essential, have distinct functions in memory formation. These two isoforms have common glutamine-rich and RNA-binding domains, yet Orb2A uniquely requires the former and Orb2B the latter. We further show that Orb2A induces Orb2 complexes in a manner dependent upon both its glutamine-rich region and neuronal activity. We propose that Orb2B acts as a conventional CPEB to regulate transport and/or translation of specific mRNAs, whereas Orb2A acts in an unconventional manner to form stable Orb2 complexes that are essential for memory to persist.

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    02/17/12 | Drosophila melanogaster as a model to study drug addiction.
    Kaun KR, Devineni AV, Heberlein U
    Human Genetics. 2012 Feb 17;131(6):959-75. doi: 10.1007/s00439-012-1146-6

    Animal studies have been instrumental in providing knowledge about the molecular and neural mechanisms underlying drug addiction. Recently, the fruit fly Drosophila melanogaster has become a valuable system to model not only the acute stimulating and sedating effects of drugs but also their more complex rewarding properties. In this review, we describe the advantages of using the fly to study drug-related behavior, provide a brief overview of the behavioral assays used, and review the molecular mechanisms and neural circuits underlying drug-induced behavior in flies. Many of these mechanisms have been validated in mammals, suggesting that the fly is a useful model to understand the mechanisms underlying addiction.

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    05/14/12 | DRP1-dependent mitochondrial fission initiates follicle cell differentiation during Drosophila oogenesis.
    Mitra K, Rikhy R, Lilly M, Lippincott-Schwartz J
    The Journal of cell biology. 2012 May 14;197(4):487-97. doi: 10.1083/jcb.201110058

    Exit from the cell cycle is essential for cells to initiate a terminal differentiation program during development, but what controls this transition is incompletely understood. In this paper, we demonstrate a regulatory link between mitochondrial fission activity and cell cycle exit in follicle cell layer development during Drosophila melanogaster oogenesis. Posterior-localized clonal cells in the follicle cell layer of developing ovarioles with down-regulated expression of the major mitochondrial fission protein DRP1 had mitochondrial elements extensively fused instead of being dispersed. These cells did not exit the cell cycle. Instead, they excessively proliferated, failed to activate Notch for differentiation, and exhibited downstream developmental defects. Reintroduction of mitochondrial fission activity or inhibition of the mitochondrial fusion protein Marf-1 in posterior-localized DRP1-null clones reversed the block in Notch-dependent differentiation. When DRP1-driven mitochondrial fission activity was unopposed by fusion activity in Marf-1-depleted clones, premature cell differentiation of follicle cells occurred in mitotic stages. Thus, DRP1-dependent mitochondrial fission activity is a novel regulator of the onset of follicle cell differentiation during Drosophila oogenesis.

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    Cardona Lab
    01/01/12 | Efficient automatic 3D-reconstruction of branching neurons from EM data.
    Funke J, Andres B, Hamprecht F, Cardona A, Cook M
    Computer Vision and Pattern Recognition (CVPR), 2012 IEEE Conference on. 2012:

    We present an approach for the automatic reconstruction of neurons from 3D stacks of electron microscopy sections. The core of our system is a set of possible assignments, each of which proposes with some cost a link between neuron regions in consecutive sections. These can model the continuation, branching, and end of neurons. The costs are trainable on positive assignment samples. An optimal and consistent set of assignments is found for the whole volume at once by solving an integer linear program. This set of assignments determines both the segmentation into neuron regions and the correspondence between such regions in neighboring slices. For each picked assignment, a confidence value helps to prioritize decisions to be reviewed by a human expert. We evaluate the performance of our method on an annotated volume of neural tissue and compare to the current state of the art [26]. Our method is superior in accuracy and can be trained using a small number of samples. The observed inference times are linear with about 2 milliseconds per neuron and section.

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    Cardona LabSaalfeld LabFetter Lab
    07/01/12 | Elastic volume reconstruction from series of ultra-thin microscopy sections.
    Saalfeld S, Fetter RD, Cardona A, Tomancak P
    Nature Methods. 2012 Jul;9(7):717-20. doi: 10.1038/nmeth.2072

    Anatomy of large biological specimens is often reconstructed from serially sectioned volumes imaged by high-resolution microscopy. We developed a method to reassemble a continuous volume from such large section series that explicitly minimizes artificial deformation by applying a global elastic constraint. We demonstrate our method on a series of transmission electron microscopy sections covering the entire 558-cell Caenorhabditis elegans embryo and a segment of the Drosophila melanogaster larval ventral nerve cord.

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    Card Lab
    04/01/12 | Escape behaviors in insects.
    Card GM
    Current Opinion in Neurobiology. 2012 Apr;22:180-6. doi: 10.1016/j.conb.2011.12.009

    Escape behaviors are, by necessity, fast and robust, making them excellent systems with which to study the neural basis of behavior. This is especially true in insects, which have comparatively tractable nervous systems and members who are amenable to manipulation with genetic tools. Recent technical developments in high-speed video reveal that, despite their short duration, insect escape behaviors are more complex than previously appreciated. For example, before initiating an escape jump, a fly performs sophisticated posture and stimulus-dependent preparatory leg movements that enable it to jump away from a looming threat. This newfound flexibility raises the question of how the nervous system generates a behavior that is both rapid and flexible. Recordings from the cricket nervous system suggest that synchrony between the activity of specific interneuron pairs may provide a rapid cue for the cricket to detect the direction of an approaching predator and thus which direction it should run. Technical advances make possible wireless recording from neurons while locusts escape from a looming threat, enabling, for the first time, a direct correlation between the activity of multiple neurons and the time-course of an insect escape behavior.

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    07/12/12 | Estimation theoretic measure of resolution for stochastic localization microscopy.
    Fitzgerald JE, Lu J, Schnitzer MJ
    Physical review letters. 2012 Jul 27;109(4):048102. doi: 10.1103/PhysRevLett.109.048102

    One approach to super-resolution fluorescence microscopy, termed stochastic localization microscopy, relies on the nanometer scale spatial localization of individual fluorescent emitters that stochastically label specific features of the specimen. The precision of emitter localization is an important determinant of the resulting image resolution but is insufficient to specify how well the derived images capture the structure of the specimen. We address this deficiency by considering the inference of specimen structure based on the estimated emitter locations. By using estimation theory, we develop a measure of spatial resolution that jointly depends on the density of the emitter labels, the precision of emitter localization, and prior information regarding the spatial frequency content of the labeled object. The Nyquist criterion does not set the scaling of this measure with emitter number. Given prior information and a fixed emitter labeling density, our resolution measure asymptotes to a finite value as the precision of emitter localization improves. By considering the present experimental capabilities, this asymptotic behavior implies that further resolution improvements require increases in labeling density above typical current values. Our treatment also yields algorithms to enhance reliable image features. Overall, our formalism facilitates the rigorous statistical interpretation of the data produced by stochastic localization imaging techniques.

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    01/01/12 | Evolution of multiple additive loci caused divergence between Drosophila yakuba and D. santomea in wing rowing during male courtship.
    Cande J, Andolfatto P, Prud'homme B, Stern DL, Gompel N
    PLoS One. 2012;7(8):e43888. doi: 10.1371/journal.pone.0043888

    In Drosophila, male flies perform innate, stereotyped courtship behavior. This innate behavior evolves rapidly between fly species, and is likely to have contributed to reproductive isolation and species divergence. We currently understand little about the neurobiological and genetic mechanisms that contributed to the evolution of courtship behavior. Here we describe a novel behavioral difference between the two closely related species D. yakuba and D. santomea: the frequency of wing rowing during courtship. During courtship, D. santomea males repeatedly rotate their wing blades to face forward and then back (rowing), while D. yakuba males rarely row their wings. We found little intraspecific variation in the frequency of wing rowing for both species. We exploited multiplexed shotgun genotyping (MSG) to genotype two backcross populations with a single lane of Illumina sequencing. We performed quantitative trait locus (QTL) mapping using the ancestry information estimated by MSG and found that the species difference in wing rowing mapped to four or five genetically separable regions. We found no evidence that these loci display epistasis. The identified loci all act in the same direction and can account for most of the species difference.

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