Prober Lab | California Institute of Technology

Developmental timecourse of larval zebrafish hypocretin neuron development.


Cindy N. Chiu*, Jason Rihel*, Daniel A. Lee, Chanpreet Singh, Eric A. Mosser, Shijia Chen, Viveca Sapin, Uyen Pham, Jae Engle, Brett J. Niles, Christin J. Montz, Sridhara Chakravarthy, Steven Zimmerman, Kourosh Salehi-Ashtiani, Marc Vidal, Alexander F. Schier and David A. Prober. (2016). A zebrafish genetic screen identifies neuromedin U as a regulator of sleep/wake states. Neuron 89, 842-856. doi: 10.1016/j.neuron.2016.01.007. * equal contribution


Audrey Chen*, Cindy N. Chiu*, Eric A. Mosser, Sohini Khan, Rory Spence and David A. Prober. (2016). QRFP and its receptors regulate locomotor activity and sleep in zebrafish. Journal of Neuroscience 36, 1823-1840. doi: 10.1523/jneurosci.2579-15.2016. * equal contribution

Shijia Chen*, Cindy N. Chiu*, Kimberley L. McArthur, Joseph R. Fetcho and David A. Prober. (2016). TRP channel mediated neuronal activation and ablation in freely behaving zebrafish. Nature Methods 13, 147-150. doi: 10.1038/nmeth.3691. * equal contribution

Chanpreet Singh*, Grigorios Oikonomou* and David A. Prober. (2015). Norepinephrine is required to promote wakefulness and for hypocretin-induced arousal in zebrafish. Elife 4. doi: 10.7554/eLife.07000.

* equal contribution



Jason Rihel*, David A. Prober*, Anthony Arvanites, Kelvin Lam, Steven Zimmerman, Sumin Jang, Stephen J. Haggarty, David Kokel, Lee L. Rubin, Randall T. Peterson and Alexander F. Schier. (2010). Zebrafish behavioral profiling links drugs to biological targets and rest/wake regulation. Science 327, 348-351. doi: 10.1126/science.1183090. * equal contribution


Eva A Naumann*, Adam R. Kampff *, David A Prober, Alexander F. Schier and Florian Engert. (2010). Monitoring neural activity with bioluminescence during natural behavior. Nature Neuroscience 13, 513-520. doi: 10.1038/nn.2518. * equal contribution

Jason Rihel, David A. Prober and Alexander F. Schier. (2010). Monitoring sleep and arousal in zebrafish. Methods in Cell Biology 100, 281-294. doi: 10.1016/B978-0-12-384892-5.00011-6.


David A. Prober, Steven Zimmerman, Benjamin R. Myers, Brian M. McDermott Jr, Seok-Hyung Kim, Sophie Caron, Jason Rihel, Lilianna Solnica-Krezel, David Julius, A.J. Hudspeth and Alexander F. Schier. (2008). Zebrafish TRPA1 channels are required for chemosensation but not for thermosensation or mechanosensory hair cell function. Journal of Neuroscience 28, 10102-10110. doi: 10.1523/jneurosci.2740-08.2008.

David A. Prober, Jason Rihel, Anthony A. Onah, Rou-Jia Sung and Alexander F. Schier (2006). Hypocretin/Orexin overexpression induces an insomnia-like phenotype in zebrafish. Journal of Neuroscience 25(51):134000-13410.


BBC World Service Interview

Larval zebrafish QRFP neurons labeled with EGFP and vip neurons labeled by in situ hybridization.
Lhx9 is sufficient to induce ectopic hypocretin neurons and is required to specify endogenous hypocretin neurons.
Neuromodulators and neuropeptides that regulate sleep are anatomically conserved in mammals and zebrafish.
TALENs are more effective than ZFNs in inducing indels in zebrafish.
Clustergram showing results of larval zebrafish small molecule screen for rest/wake phenotypes.
Larval zebrafish TRPA1a and TRPA1b are required for behavioral responses to mustard oil but not to noxious heat or cold.

David A. Prober and Bruce A. Edgar. (2002). Interactions between Ras1, dMyc, and dPI3K signaling in the developing Drosophila wing. Genes and Development 16, 2286-2299. [ Article ]

David A. Prober and Bruce A. Edgar. (2001). Growth regulation by oncogenes - new insights from model organisms. Current Opinion in Genetics and Development 11, 19-26. [ Article ]

David A. Prober and Bruce A. Edgar. (2000). Ras1 promotes cellular growth in the Drosophila wing. Cell 100, 435-446. [ Article ]

Laura A. Johnston, David A. Prober, Bruce A. Edgar, Robert N. Eisenman and Peter Gallant. (1999). Drosophila myc regulates cellular growth during development. Cell 98, 779-790. [ Article ]

Christine L. Hall, Laurie A. Lange, David A. Prober, Shiwen Zhang and Eva A. Turley. (1996). pp60(c-src) is required for cell locomotion regulated by the hyaluronan receptor RHAMM. Oncogene 13, 2213-2224.

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Earlier publications

Justin Liu, Florian T. Merkle, Avni V. Gandhi, James A. Gagnon, Ian G. Woods, Cindy N. Chiu, Tomomi Shimogori, Alexander F. Schier and David A. Prober. (2015). Evolutionarily conserved regulation of hypocretin neuron specification by Lhx9. Development 142, 1113-1124. doi: 10.1242/dev.117424.

Cindy N. Chiu and David A. Prober. (2013). Regulation of zebrafish sleep and arousal states: current and prospective approaches. Frontiers in Neural Circuits 7:58. doi: 10.3389/fncir.2013.00058.

Shijia Chen*, Grigorios Oikonomou*, Cindy N. Chiu, Brett J. Niles, Justin Liu, Daniel A. Lee, Igor Antoshechkin and David A. Prober. (2013). A large-scale in vivo analysis reveals that TALENs are significantly more mutagenic than ZFNs generated using context-dependent assembly. Nucleic Acids Research 41, 2769-2778. doi: 10.1093/nar/gks1356. * equal contribution

Avni V. Gandhi, Eric A. Mosser, Grigorios Oikonomou and David A. Prober. (2015). Melatonin is required for the circadian regulation of sleep. Neuron 85, 1193-1199. doi: 10.1016/j.neuron.2015.02.016.

Prober lab publications in Pubmed

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Cell Press podcast

Larval zebrafish with pineal gland labeled with CFP-NTR and aanat2 in situ hybridization (left) and immunohistochemistry for serotonin (5-HT) in the pineal gland of aanat2+/- and aanat2-/- larvae during the day and night.
Hypocretin neurons (red) project to noradrenergic neurons (green) in the locus coeruleus (A) and medulla oblongata (B)

Paula Suarez-Bregua, Eva Torres-Nunez, Ankur Saxena, Pedro Guerreiro, Ingo Braasch, David A. Prober, Paloma Moran, Jose Miguel Cerda-Reverter, Shao Jun Du, Fatima Adrio, Deborah M. Power, Adelino V.M. Canario, John H. Postlethwait, Marianne E. Bronner, Cristian Canestro and Josep Rotllant. (2016). Pth4, an ancient parathyroid hormone lost in eutherian mammals, reveals a new brain-to-bone signaling pathway. FASEB Journal 31, 569-583. doi: 10.1096/fj.201600815R. [ Article ]

Harry M.T. Choi, Colby R. Calvert, Naeem Husain, David Huss, Julius C. Barsi, Benjamin E. Deverman, Ryan C. Hunter, Mihoko Kato, S. Melanie Lee, Anna C.T. Abelin, Adam Z. Rosenthal, Omar S. Akbari, Yuwei Li, Bruce A. Hay, Paul W. Sternberg, Paul H. Patterson, Eric H. Davidson, Sarkis K. Mazmanian, David A. Prober, Mat van de Rijn, Jared R. Leadbetter, Dianne K. Newman, Carol Readhead, Marianne E. Bronner, Barbara Wold, Rusty Lansford, Tatjana Sauka-Spengler, Scott E. Fraser and Niles A. Pierce (2016). Mapping a multiplexed zoo of mRNA expression. Development 143, 3632-3637. doi: 10.1242/dev.14037.  [ Article ]

Yali Zhao, Chanpreet Singh, David A. Prober and Nancy L. Wayne (2016). Morphological and physiological interactions between GnRH3 and hypocretin/orexin neuronal systems in zebrafish (Danio rerio). Endocrinology 157, 4012-4020. doi: 10.1210/en.2016-1381. [ Article ]

Grigorios Oikonomou and David A. Prober. (2017). Attacking sleep from a new angle: contributions from zebrafish. Current Opinion in Neurobiology 44, 80-88. doi: 10.1016/j.conb.2017.03.009. [ Article ]

Audrey Chen, Chanpreet Singh, Grigorios Oikonomou and David A. Prober. (2017). Genetic analysis of histamine signaling in larval zebrafish sleep. eNeuro 4(1). doi: 10.1523/ENEURO.0286-16.2017. [ Article ]