Primary Faculty

Herwig Baier

Genetic Architecture of Visual Perception and Behavior

Research Description

From gene to behavior

We are interested in the molecular and cellular mechanisms underlying animal behavior. The genes that prescribe the assembly and function of the nervous system form a complex network, acting in changing combinations, in different tissues and at different developmental stages. In order to gain insights into the genetic architecture of behavior, we are searching for the genes that play specific roles in a given behavioral process. The litmus test for an individual gene’s requirement is its loss-of-function phenotype. Forward genetic screens provide an unbiased strategy for the discovery of these genes.

Zebrafish (Danio rerio) provides three main advantages for a genetic approach to behavior:

• Optics: The zebrafish brain is transparent from embryonic well into larval stages, allowing in vivo imaging of fluorescently labeled neurons, as well as their neurites and synapses.

• Genetics: Forward-genetic screens can be carried out for the purpose of gene discovery. Moreover, we are employing transgenic probes that are designed to interfere with neuronal activity as a novel tool for circuit analysis.

• Psychophysics: Precise measurements of behavior and perception are possible in zebrafish. For example, it is straightforward to evoke behavioral responses by exposing fish larvae to computer-generated visual stimuli and to quantify the frequency and magnitude of these responses.

Behavioral assays

In zebrafish, visual motion of large-field gratings elicits two innate reflexes, the optomotor response (OMR) and the optokinetic response (OKR) [click to watch movies]. To build a catalog of genes important for the execution of OMR and OKR, we are screening for mutations that disrupt (or otherwise alter) either or both of these responses in mutagenized zebrafish. Hundreds of thousands of mutagenized animals can be generated for our experiments, and their visual and motor abilities can be assessed in high-throughput screens. We have already discovered 70 specific mutations that cause a broad spectrum of visual dysfunctions. Each mutation has tagged an important gene, which can be positionally cloned, and each identified gene serves as an entry point into a molecular process essential for normal vision.
Besides continuing our studies of OMR and OKR, we are now also investigating capture of prey (paramecia), as well as energy balance and mating behaviors. These are potentially suitable for a systematic analysis of neuronal circuitry. [Click to watch prey capture movie].

From circuit to behavior

In addition to our gene discovery approach, the lab has recently moved into the area of neuronal circuit analysis, using targeted manipulations of synaptic activity in genetically defined subpopulations of neurons.

Our collaborators in these and other projects include the labs of Holly Ingraham (UCSF), Didier Stainier (UCSF), Hao Li (UCSF), Jeff Chuang (Boston University), Rachel O. Wong (Washington University, now U Washington), Mu-ming Poo (UC Berkeley), Huizhong Tao (USC), Brian Link (Medical College of Wisconsin), Stephen J. Smith (Stanford), Ehud Isacoff (UC Berkeley), and Juan Korenbrot (UCSF).

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Current Projects

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Selected Publications

Gosse N.J., Nevin L.M., Baier H. Retinotopic order in the absence of axon competition. Nature 452: 892-895 (2008).

Xiao T., Baier H. Lamina-specific axonal projections in the zebrafish tectum require the type IV collagen Dragnet. Nature Neuroscience, 10: 1529-1537 (2007).

Del Bene F., Ettwiller L., Skowronska-Krawczyk D., Baier H., Matter J.M., Birney E., Wittbrodt J. In vivo validation of a computationally predicted conserved Ath5 target gene set. PLoS Genetics 3: 1661-71 (2007).

Szobota S, Gorostiza P, Del Bene F, Wyart C, Fortin DL, Kolstad KD, Tulyathan O, Volgraf M, Numano R, Aaron HL, Scott EK, Kramer RH, Flannery J, Baier H, Trauner D, Isacoff EY. (2007) Remote control of neuronal activity with a light-gated glutamate receptor.  Neuron. 54(4):535-45.

Scott IC, Masri B, D'Amico LA, Jin SW, Jungblut B, Wehman AM, Baier H, Audigier Y, Stainier DY. (2007)   The g protein-coupled receptor agtrl1b regulates early development of myocardial progenitors.  Dev Cell. 12(3):403-13

Davison JM, Akitake CM, Goll MG, Rhee JM, Gosse N, Baier H, Halpern ME, Leach SD, Parsons MJ. (2007) Transactivation from Gal4-VP16 transgenic insertions for tissue-specific cell labeling and ablation in zebrafish.  Dev Biol. 304(2):811-24

Campbell DS, Stringham SA, Timm A, Xiao T, Law MY, Baier H, Nonet ML, Chien CB. (2007) Slit1a inhibits retinal ganglion cell arborization and synaptogenesis via Robo2-dependent and -independent pathways.  Neuron. 55(2):231-45

Jin SW, Herzog W, Santoro MM, Mitchell TS, Frantsve J, Jungblut B, Beis D, Scott IC, D'Amico LA, Ober EA, Verkade H, Field HA, Chi NC, Wehman AM, Baier H, Stainier DY. (2007) A transgene-assisted genetic screen identifies essential regulators of vascular development in vertebrate embryos.  Dev Biol. 307(1):29-42

Scott EK, Mason L, Arrenberg AB, Ziv L, Gosse NJ, Xiao T, Chi NC, Asakawa K, Kawakami K, Baier H (2007) Targeting neural circuitry in zebrafish using GAL4 enhancer trapping. Nature Methods 4(4): 323-6 - Supplementary Data

Smear MC, Tao HW, Staub W, Orger MB, Gosse NJ, Liu Y, Takahashi KD, Poo MM, Baier H (2007) Vesicular glutamate transport at a central synapse limits the the acuity of visual perception in zebrafish. Neuron 53: 65-77.

Wehman A, Staub W, Baier H (2006) The anaphase-promoting complex is required in both dividing and quiescent cells during zebrafish development. Developmental Biology doi:10.1016/j.jdbio.2006.10.043.

Mumm J, Williams P, Godhinho L, Koerber A, Pittman A, Roeser T, Chien C, Baier H, Wong R (2006) In Vivo Imaging Reveals Dendritic Targeting of Laminated Afferents by Zebrafish Retinal Ganglion Cells. Neuron 52:609-21.

Muto A, Orger M, Wehman A, Smear M, Kay J, Page-McCaw P, Gahtan E, Xiao T, Nevin L, Gosse N, Staub W, Finger-Baier K, Baier H (2005) Forward genetic analysis of visual behavior in zebrafish. PLoS Genetics 1:575-88.

Gahtan E, Tanger P, Baier H (2005) Visual prey capture in larval zebrafish is controlled by identified reticulospinal neurons downstream of the tectum. Journal of Neuroscience 25:9294-303.

Beis D, Bartman T, Jin SW, Scott IC, D'Amico LA, Ober EA, Verkade H, Frantsve J, Field HA, Wehman A, Baier H, Tallafuss A, Bally-Cuif L, Chen JN, Stainier DY, Jungblut B (2005) Genetic and cellular analyses of zebrafish atrioventricular cushion and valve development. Development 132:4193-204.

Orger MB, Baier H (2005) Channeling of red and green cone inputs to the zebrafish optomotor response. Visual Neuroscience 22:275-81.

Xiao T, Roeser T, Staub W, Baier H (2005) A GFP-based genetic screen reveals mutations that disrupt the architecture of the zebrafish retinotectal projection. Development 132:2955-67.

Kay JN, Link BA, Baier H (2005) Staggered cell-intrinsic timing of ath5 expression underlies the wave of ganglion cell neurogenesis in the zebrafish retina. Development 132:2573-85.

Wehman AM, Staub W, Meyers JR, Raymond PA, Baier H (2005) Genetic dissection of the zebrafish retinal stem-cell compartment. Developmental Biology 281:53-65.

Hua JY, Smear MC, Baier H, Smith SJ (2005) Regulation of axon growth in vivo by activity-based competition. Nature 434:1022-6.

Baraban SC, Taylor MR, Castro PA, Baier H (2005) Pentylenetetrazole induced changes in zebrafish behavior, neural activity and c-fos expression. Neuroscience 131:759-68.

Orger MB, Gahtan E, Muto A, Page-McCaw P, Smear MC, Baier H (2004) Behavioral screening assays in zebrafish. Methods in Cell Biology: Zebrafish Genetics & Genomics 77:53-68.

Page-McCaw PS, Chung SC, Muto A, Roeser T, Staub W, Finger-Baier KC, Korenbrot JI, Baier H (2004) Retinal network adaptation to bright light requires tyrosinase. Nature Neuroscience 7:1329-36.

Kay JN, Baier H (2004) Out-foxing fate; molecular switches create neuronal diversity in the retina. Neuron 43:759-60.

Gahtan E, Baier H (2004) Of lasers, mutants, and see-through brains: functional neuroanatomy in zebrafish. Journal of Neurobiology 59:147-61.

Kay JN, Roeser T, Mumm JS, Godinho L, Mrejeru A, Wong RO, Baier H (2004) Transient requirement for ganglion cells during assembly of retinal synaptic layers. Development 131:1331-42.

Goldsmith P, Baier H, Harris WA (2003) Two zebrafish mutants, ebony and ivory, uncover benefits of neighborhood on photoreceptor survival. Journal of Neurobiology 57:235-45.

Loosli F, Staub W, Finger-Baier KC, Ober EA, Verkade H, Wittbrodt J, Baier H (2003) Loss of eyes in zebrafish caused by mutation of chokh/rx3. EMBO Reports 4:894-9.

Roeser T, Baier H (2003) Visuomotor behaviors in larval zebrafish after GFP-guided laser ablation of the optic tectum. Journal of Neuroscience 23:3726-34.

Kay JN, Finger-Baier KC, Roeser T, Staub W, Baier H (2001) Retinal ganglion cell genesis requires lakritz, a zebrafish atonal homolog. Neuron 30:725-36.

Orger MB, Smear MC, Anstis SM, Baier H (2000) Perception of Fourier and non-Fourier motion by larval zebrafish. Nature Neuroscience 3:1128-33.

Baier H (2000) Zebrafish on the move: towards a behavior-genetic analysis of vertebrate vision. Current Opinion in Neurobiology 10:451-5.

Baier H, Copenhagen D (2000) Combining physiology and genetics in the zebrafish retina. Journal of Physiology 524:1.

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Contact Information

Email: herwig.baier@ucsf.edu
Phone: 415-502-4301
Mailing Address:
UCSF, Rock Hall
Box 2722
1550 4th ST, 19B 348F
San Francisco, CA 94143-2722

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