RESEARCH INTERESTS
The zebrafish is a powerful system for genetic studies of neural development because of its short generation time and ability to produce large numbers of progeny. Eggs are fertilized externally, the resultant embryos develop rapidly and are optically clear, allowing direct visualization of the newly forming nervous system and identification of mutant phenotypes. More recently, fluorescent reporters have been a valuable tool for monitoring cell behavior in live transgenic embryos. The zebrafish larva is also ideally suited for optical methods to modulate neuronal activity.
One of the questions my laboratory has been studying is how differences are established between the left and right sides of the developing brain. In fish, amphibians and reptiles, the dorsal most region of the diencephalon, the epithalamus, exhibits notable left-right asymmetry in structure and in gene expression. Such differences also affect neural connections onto the midbrain target and, presumably, influence behavior.
We have been performing screens to identify the genes that control asymmetry of the brain and we have developed methods to perturb laterality. Larval and adult fish with altered brains (left-right reversed or both sides with right identity) are being used in behavioral assays to determine the function of epithalamic asymmetry (Facchin et al., 2009). We are also working on in vivo methods to visualize neural connections in the brains of altered and normal individuals.
In other work, we have been generating new transgenic lines to monitor fluorescently labeled cells in the living brain, such as myelinating glia, or to perturb specific subregions by localized cell ablation. In addition, epigenetic regulation of gene expression (i.e., gene silencing) in the brain can be readily monitored using fluorescent transgenic reporters (Goll et al. 2009). With converging mutational and transgenic approaches, we hope to gain new insights into the developing nervous system and, ultimately, the neural control of behavioral responses.
REPRESENTATIVE PUBLICATIONS
Asymmetric nodal signaling in the zebrafish diencephalon positions the pineal organ.
Liang JO, Etheridge A, Hantsoo L, Rubinstein AL, Nowak SJ, Izpisúa Belmonte JC, Halpern ME. Development. 2000 Dec;127(23):5101-12.
Origin and specification of the neural tube floor plate: insights from the chick and zebrafish.
Le Douarin NM, Halpern ME. Curr Opin Neurobiol. 2000 Feb;10(1):23-30.
Genetic analysis of digestive physiology using fluorescent phospholipid reporters.
Farber SA, Pack M, Ho SY, Johnson ID, Wagner DS, Dosch R, Mullins MC, Hendrickson HS, Hendrickson EK, Halpern ME. Science. 2001 May 18;292(5520):1385-8.
Otx5 regulates genes that show circadian expression in the zebrafish pineal complex.
Gamse JT, Shen YC, Thisse C, Thisse B, Raymond PA, Halpern ME, Liang JO. Nat Genet. 2002 Jan;30(1):117-21. Epub 2001 Dec 20.
Characterization of myelination in the developing zebrafish.
Brösamle C, Halpern ME. Glia. 2002 Jul;39(1):47-57.
The parapineal mediates left-right asymmetry in the zebrafish diencephalon.
Gamse JT, Thisse C, Thisse B, Halpern ME. Development. 2003 Mar;130(6):1059-68.
Radiographic analysis of zebrafish skeletal defects.
Fisher S, Jagadeeswaran P, Halpern ME. Dev Biol. 2003 Dec 1;264(1):64-76.
Leaning to the left: laterality in the zebrafish forebrain.
Halpern ME, Liang JO, Gamse JT. Trends Neurosci. 2003 Jun;26(6):308-13. Review.
Directional asymmetry of the zebrafish epithalamus guides dorsoventral innervation of the midbrain target.
Gamse JT, Kuan YS, Macurak M, Brösamle C, Thisse B, Thisse C, Halpern ME. Development. 2005 Nov;132(21):4869-81. Epub 2005 Oct 5.
Neuropilin asymmetry mediates a left-right difference in habenular connectivity.
Kuan YS, Yu HH, Moens CB, Halpern ME. Development. 2007 Mar;134(5):857-65. Epub 2007 Jan 24.
Evolving into science advocates.
Halpern ME, Hobin JA. Dev Dyn. 2008 May;237(5):1215-7. No abstract available.
Gal4/UAS transgenic tools and their application to zebrafish.
Halpern ME, Rhee J, Goll MG, Akitake CM, Parsons M, Leach SD. Zebrafish. 2008 Summer;5(2):97-110. Review.
Nogo-Nogo receptor signalling in PNS axon outgrowth and pathfinding.
Brösamle C, Halpern ME. Mol Cell Neurosci. 2009 Apr;40(4):401-9. Epub 2008 Nov 8.
Determining the function of zebrafish epithalamic asymmetry.
Facchin L, Burgess HA, Siddiqi M, Granato M, Halpern ME. Philos Trans R Soc Lond B Biol Sci. 2009 Apr 12;364(1519):1021-32.
Transcriptional silencing and reactivation in transgenic zebrafish.
Goll MG, Anderson R, Stainier DY, Spradling AC, Halpern ME. Genetics. 2009 Jul;182(3):747-55. Epub 2009 May 11.
LAB MEMBERS
Sang Jung Ahn, P/D Assoc.
Courtney Akitake, Predoc Fellow
Molly Broache, Student Assistant
Tagide deCarvalho, P/D Assoc.
Lucilla Facchin, P/D Assoc.
Lea Fortuno, Technician
Mary Goll, P/D Assoc.
Dan Gorelick, P/D Fellow
Amy Herbert, Student Volunteer
Adam Kim, Rotation Student
Michelle Macurak, Technician
Vanessa Matos-Cruz, Predoc Fellow
Alex Yeh, Student Assistant
