Faculty Profile

As many as 10% of Americans suffer chronic sleep disturbances, but the genetic and cellular mechanisms that control sleep and wake states remain largely elusive. We wish to find genes and circuits that regulate this behavior. We are establishing zebrafish as a model system for sleep research. Zebrafish have the basic hallmarks of sleep-like behaviors. Sleeping fish require stronger stimuli than awake fish to initiate movement (increased arousal threshold), and sleep deprivation is followed by increased sleep (sleep rebound).

In addition, the zebrafish brain expresses peptides that have been implicated in human sleep disorders. We have developed assays to measure sleep and wakefulness in zebrafish and used the hypocretin/orexin system as a proof-of-principle that the genetic and molecular basis of sleep regulation is conserved between fish and mammals. Our long-term goals are to employ in vivo imaging to analyze the neural circuits regulating sleep and to use genetic and drug screens to isolate novel sleep regulators.

Postdoctoral fellows:
Dr. David Prober (Helen Hay Whitney Fellow 2003-2006; K99 Fellow 2007-2009)
Dr. Jason Rihel (Fellow of the Life Sciences Foundation 2005-2008)
Dr. David Schoppik (Helen Hay Whitney Fellow 2008-2011)
Dr. Florian Merkle (Jane Coffin Childs Memorial Fund Fellow 2008-2011)

Current funding:
NIH
"Genetic Mechanisms of Axis Formation in Vertebrates"

NIH
"Comparative genetics of gli function"

NIH
"Genetics of Sleep in Zebrafish"

McKnight Neuroscience of Brain Disorders Award
"Genetic analysis of sleep disorders in zebrafish"

Schier AF, Needleman D. Developmental biology: Rise of the source-sink model.
Nature. 2009 Sep 24;461(7263):480-1. [PMID: 19779439]

Huang P, Schier AF. Dampened Hedgehog signaling but normal Wnt signaling in zebrafish without cilia.
Development. 2009 Sep;136(18):3089-98. [PMID:19700616]

de Campos-Baptista MI, Holtzman NG, Yelon D, Schier AF. Nodal signaling promotes the speed and directional movement of cardiomyocytes in zebrafish.
Dev Dyn. 2008 Dec;237(12):3624-33. [PMID: 18985714]

Caron SJ, Prober D, Choy M, Schier AF. In vivo birthdating by BAPTISM reveals that trigeminal sensory neuron diversity depends on early neurogenesis.
Development. 2008 Oct;135(19):3259-69. Epub 2008 Aug 28. [PMID: 18755773]

Prober DA, Zimmerman S, Myers BR, McDermott BM Jr, Kim SH, Caron S, Rihel J, Solnica-Krezel L, Julius D, Hudspeth AJ, Schier AF. Zebrafish TRPA1 channels are required for chemosensation but not for thermosensation or mechanosensory hair cell function.
J Neurosci. 2008 Oct 1;28(40):10102-10. [PMID: 18829968]

Douglass AD, Kraves S, Deisseroth K, Schier AF, Engert F. Escape behavior elicited by single, channelrhodopsin-2-evoked spikes in zebrafish somatosensory neurons.
Curr Biol. 2008 Aug 5;18(15):1133-7. [PMID: 18682213]

Woods IG, Schier AF. Targeted mutagenesis in zebrafish.
Nat Biotechnol. 2008 Jun;26(6):650-1. [PMID: 18536686]

Knaut H, Schier AF. Clearing the path for germ cells.
Cell. 2008 Feb 8;132(3):337-9. [PMID: 18267065]

Choi PS, Zakhary L, Choi WY, Caron S, Alvarez-Saavedra E, Miska EA, McManus M, Harfe B, Giraldez AJ, Horvitz HR, Schier AF, Dulac C. Members of the miRNA-200 family regulate olfactory neurogenesis.
Neuron. 2008 Jan 10;57(1):41-55. [PMID: 18184563]

Bennett JT, Stickney HL, Choi WY, Ciruna B, Talbot WS, Schier AF. Maternal nodal and zebrafish embryogenesis.
Nature. 2007 Nov 8;450(7167):E1-2; discussion E2-4. [PMID: 17994032]

Karkera JD, Lee JS, Roessler E, Banerjee-Basu S, Ouspenskaia MV, Mez J, Goldmuntz E, Bowers P, Towbin J, Belmont JW, Baxevanis AD, Schier AF, Muenke M. Loss-of-function mutations in growth differentiation factor-1 (GDF1) are associated with congenital heart defects in humans.
Am J Hum Genet. 2007 Nov;81(5):987-94. Epub 2007 Sep 28. [PMID: 17924340]

Choi WY, Giraldez AJ, Schier AF. Target protectors reveal dampening and balancing of Nodal agonist and antagonist by miR-430.
Science. 2007 Oct 12;318(5848):271-4. [PMID: 17761850]

Schier AF. The maternal-zygotic transition: death and birth of RNAs.
Science. 2007 Apr 20;316(5823):406-7. Review. [PMID: 17446392]

Bennett JT, Joubin K, Cheng S, Aanstad P, Herwig R, Clark M, Lehrach H, Schier AF. Nodal signaling activates differentiation genes during zebrafish gastrulation.
Dev Biol. 2007 Apr 15;304(2):525-40. Epub 2007 Jan 12. [PMID: 17306247]

Prober DA, Rihel J, Onah AA, Sung RJ, Schier AF. Hypocretin/orexin overexpression induces an insomnia-like phenotype in zebrafish.
J Neurosci. 2006 Dec 20;26(51):13400-10. [PMID: 17182791]

Mishima Y, Giraldez AJ, Takeda Y, Fujiwara T, Sakamoto H, Schier AF, Inoue K. Differential regulation of germline mRNAs in soma and germ cells by zebrafish miR-430.
Curr Biol. 2006 Nov 7;16(21):2135-42. [PMID: 17084698]

Obara T, Mangos S, Liu Y, Zhao J, Wiessner S, Kramer-Zucker AG, Olale F, Schier AF, Drummond IA. Polycystin-2 immunolocalization and function in zebrafish.
J Am Soc Nephrol. 2006 Oct;17(10):2706-18. Epub 2006 Aug 30. [PMID: 16943304]

Giraldez AJ, Mishima Y, Rihel J, Grocock RJ, Van Dongen S, Inoue K, Enright AJ, Schier AF. Zebrafish MiR-430 promotes deadenylation and clearance of maternal mRNAs.
Science. 2006 Apr 7;312(5770):75-9. [PMID: 16484454]

Ciruna B, Jenny A, Lee D, Mlodzik M, Schier AF. Planar cell polarity signalling couples cell division and morphogenesis during neurulation.
Nature. 2006 Jan 12;439(7073):220-4. [PMID: 16407953]

Reviews

Schier AF. The maternal-zygotic transition: death and birth of RNAs.
Science. 2007 Apr 20;316(5823):406-7. Review. [PMID: 17446392]

Schier AF, Giraldez AJ. MicroRNA function and mechanism: insights from zebra fish.
Cold Spring Harb Symp Quant Biol. 2006;71:195-203. Review. [PMID: 17381297]