Faculty Profile

Alexander F. Schier, PhD


Professor of Molecular and Cellular Biology, Harvard University Faculty of Arts and Sciences

Other Affiliation(s)

Center for Brain Science
Harvard Stem Cell Institute
Broad Institute

See publications


Research Interests

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 have established 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 (Prober et al. Journal of Neuroscience 2006). Most recently, we have used large-scale drug screening to dissect molecular pathways that regulate sleep and identified novel sleep regulators (Rihel et al. Science 2010). Our current goal is to employ in vivo imaging to analyze the neural circuits regulating sleep and to use genetic screens to isolate novel sleep regulators.

We are also using human stem cell technology to generate hypocretin neurons from narcoleptic subjects in order to determine the molecular basis of neural degeneration in these patients.

Website
Schier Lab

Selected Publications

Original Articles

Bianco IH, Ma LH, Schoppik D, Robson DN, Orger MB, Beck JC, Li JM, Schier AF, Engert F, Baker R. The tangential nucleus controls a gravito-inertial vestibulo-ocular reflex.
Curr Biol. 2012 Jul 24;22(14):1285-95. doi: 10.1016/j.cub.2012.05.026. Epub 2012 Jun 14. [PMID: 22704987]

Low SE, Woods IG, Lachance M, Ryan J, Schier AF, Saint-Amant L. Touch responsiveness in zebrafish requires voltage-gated calcium channel 2.1b.
J Neurophysiol. 2012 Jul;108(1):148-59. doi: 10.1152/jn.00839.2011. Epub 2012 Apr 4. [PMID: 22490555]

Vastenhouw NL, Schier AF. Bivalent histone modifications in early embryogenesis.
Curr Opin Cell Biol. 2012 Jun;24(3):374-86. doi: 10.1016/j.ceb.2012.03.009. Epub 2012 Apr 17. [PMID: 22513113]

Panizzi JR, Becker-Heck A, Castleman VH, Al-Mutairi DA, Liu Y, Loges NT, Pathak N, Austin-Tse C, Sheridan E, Schmidts M, Olbrich H, Werner C, Häffner K, Hellman N, Chodhari R, Gupta A, Kramer-Zucker A, Olale F, Burdine RD, Schier AF,  O'Callaghan C, Chung EM, Reinhardt R, Mitchison HM, King SM, Omran H, Drummond IA. CCDC103 mutations cause primary ciliary dyskinesia by disrupting assembly of ciliary dynein arms.
Nat Genet. 2012 May 13;44(6):714-9. doi: 10.1038/ng.2277. [PMID: 22581229]

Müller P, Rogers KW, Jordan BM, Lee JS, Robson D, Ramanathan S, Schier AF. Differential diffusivity of Nodal and Lefty underlies a reaction-diffusion patterning system.
Science. 2012 May 11;336(6082):721-4. doi: 10.1126/science.1221920. Epub 2012 Apr 12. [PMID: 22499809]

Ahrens MB, Li JM, Orger MB, Robson DN, Schier AF, Engert F, Portugues R. Brain-wide neuronal dynamics during motor adaptation in zebrafish.
Nature. 2012 May 9;485(7399):471-7. doi: 10.1038/nature11057. [PMID: 22622571]

Stooke-Vaughan GA, Huang P, Hammond KL, Schier AF, Whitfield TT. The role of hair cells, cilia and ciliary motility in otolith formation in the zebrafish otic vesicle.
Development. 2012 May;139(10):1777-87. doi: 10.1242/dev.079947. Epub 2012 Mar 29. [PMID: 22461562]

Xu C, Fan ZP, Müller P, Fogley R, DiBiase A, Trompouki E, Unternaehrer J, Xiong F, Torregroza I, Evans T, Megason SG, Daley GQ, Schier AF, Young RA, Zon LI. Nanog-like regulates endoderm formation through the Mxtx2-Nodal pathway.
Dev Cell. 2012 Mar 13;22(3):625-38. doi: 10.1016/j.devcel.2012.01.003. [PMID:
22421047]

Pauli A, Valen E, Lin MF, Garber M, Vastenhouw NL, Levin JZ, Fan L, Sandelin  A, Rinn JL, Regev A, Schier AF. Systematic identification of long noncoding RNAs  expressed during zebrafish embryogenesis.
Genome Res. 2012 Mar;22(3):577-91. doi: 10.1101/gr.133009.111. Epub 2011 Nov 22. [PMID: 22110045]

Pan YA, Choy M, Prober DA, Schier AF. Robo2 determines subtype-specific axonal projections of trigeminal sensory neurons.
Development. 2012 Feb;139(3):591-600. doi: 10.1242/dev.076588. Epub 2011 Dec 21. [PMID: 22190641]

Pan YA, Caron SJ, Schier AF. BAPTI and BAPTISM birthdating of neurons in zebrafish.
Cold Spring Harb Protoc. 2012 Jan 1;2012(1):87-92. doi: 10.1101/pdb.prot067520. [PMID: 22194263]

Huang P, Xiong F, Megason SG, Schier AF. Attenuation of Notch and Hedgehog signaling is required for fate specification in the spinal cord.
PLoS Genet. 2012;8(6):e1002762. doi: 10.1371/journal.pgen.1002762. Epub 2012 Jun 7. [PMID: 22685423]

Rihel J, Prober DA, Arvanites A, Lam K, Zimmerman S, Jang S, Haggarty SJ, Kokel D, Rubin LL, Peterson RT, Schier AF. Zebrafish behavioral profiling links drugs to biological targets and rest/wake regulation.
Science. 2010 Jan 15;327(5963):348-51. [PMID: 20075256]

Harvey SA, Tümpel S, Dubrulle J, Schier AF, Smith JC. no tail integrates two modes of mesoderm induction.
Development. 2010 Apr;137(7):1127-35. [PMID: 20215349]

Naumann EA, Kampff AR, Prober DA, Schier AF, Engert F. Monitoring neural activity with bioluminescence during natural behavior.
Nat Neurosci. 2010 Apr;13(4):513-20. Epub 2010 Mar 21. [PMID: 20305645]

Vastenhouw NL, Zhang Y, Woods IG, Imam F, Regev A, Liu XS, Rinn J, Schier AF. Chromatin signature of embryonic pluripotency is established during genome activation.
Nature. 2010 Apr 8;464(7290):922-6. Epub 2010 Mar 24. [PMID: 20336069]

Rihel J, Prober DA, Schier AF. Monitoring sleep and arousal in zebrafish.
Methods Cell Biol. 2010;100:281-94. [PMID: 21111222]

Rihel J, Prober DA, Arvanites A, Lam K, Zimmerman S, Jang S, Haggarty SJ, Kokel D, Rubin LL, Peterson RT, Schier AF. Zebrafish behavioral profiling links drugs to biological targets and rest/wake regulation.
Science. 2010 Jan 15;327(5963):348-51. [PMID: 20075256]

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

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]

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]

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]

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]

Books, Chapters, and Reviews

Rihel J, Schier AF. Behavioral screening for neuroactive drugs in zebrafish.
Dev Neurobiol. 2012 Mar;72(3):373-85. doi: 10.1002/dneu.20910. Review. [PMID: 21567979]

Pan, A., Livet, J., Sanes, J., Lichtman, J., and Schier, A.F. (2011). Multicolor Brainbow imaging in zebrafish.
In Imaging in Developmental Biology: A Laboratory Manual. Cold Spring Harbor Protocols.

Müller P, Schier AF. Extracellular movement of signaling molecules.
Dev Cell. 2011 Jul 19;21(1):145-58. Review. [PMID: 21763615]

Pauli A, Rinn JL, Schier AF. Non-coding RNAs as regulators of embryogenesis.
Nat Rev Genet. 2011 Feb;12(2):136-49. Review. [PMID: 21245830]

Pan, A., Caron, S. and Schier, A.F. (2010). In vivo birthdating in larval zebrafish.
In Imaging in Developmental Biology: A Laboratory Manual (CSHL Press), in press.

Rihel, J., Prober, D., and Schier, A.F. (2010). Monitoring sleep and arousal in zebrafish.
In Methods in Cell Biology: The Zebrafish 3rd Edition,100, 281-94.

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

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]

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]

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