Biomedical Research Education & Training
Faculty Member

Gamse, Joshua T., Ph. D.
Associate Professor of Cell and Developmental Biology

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Phone Number: (615) 936-5574

Email Address:

Gamse, Joshua's picture
Academic history
B.A., Rice University, Houston, TX
Ph. D., Massachusetts Institute of Technology, Cambridge, MA
Postdoctoral Fellowship, Carnegie Institution of Washington, Baltimore, MD

Office Address   Mailing Address

Room 4270, MRB III

VU Station B, Box 35-1634, Nashville, TN 37235-1634 FOR EXPRESS MAIL: Room 4270, MRB III 465 21st Ave. S, 37232

Research Keywords
Neurobiology, genetics, left-right brain asymmetry, zebrafish,Developmental biology,Genetics,Mutation,Neuroscience,Transcription factor

Research Specialty
The Gamse lab explores the development of left-right brain asymmetry.

Research Description
The left-right (L-R) axis is one of the three fundamental axes (along with the anteroposterior [A-P] and dorsoventral [D-V]) upon which the brain is patterned. Differences in neuroanatomy on the left and right sides of the brain are the substrates for asymmetrically localized functions including language and handedness in humans. Brain asymmetry in humans and other animals is a crucial and evolutionarily conserved feature that increases both the capacity and speed of multi-task performance. Additionally, reversal or reduction of asymmetric brain anatomy is linked to a number of disorders including schizophrenia and major depression.

In order for an asymmetric brain to form during development, neuronal precursors must be specified, proliferate, migrate to their destination and differentiate with appropriate characteristics. Our goal is to understand how these events are controlled along the L-R axis.

We use a vertebrate model system, zebrafish (Danio rerio), to advance our understanding of asymmetric formation of the vertebrate brain. This model organism offers two unique advantages: it is easy to assay and image L-R differences in the intact brain, and forward and reverse genetics as well as transgenesis are all readily available.

Because of its superficial location, robust molecular and anatomical L-R differences, and simple composition, the epithalamus has received the most attention in the study of asymmetric brain development. There are two major subdivisions to the epithalamus, the pineal complex and the habenular nuclei, or habenulae. The pineal complex includes the pineal organ and the parapineal organ, an accessory organ that is found unilaterally on the left side of the brain. The dorsal habenular nuclei are bilateral brain nuclei adjacent to the pineal complex. They are divided into medial and lateral subnuclei; the lateral subnucleus is larger on the left while the medial subnucleus is larger on the right.

Asymmetry of the parapineal organ and the habenular nuclei is coordinated. In brain-reversed larvae, the parapineal now innervates the right habenula. This results in the right habenula developing characteristics of the left habenula, and vice versa. Reversal of habenular asymmetry is linked to reduced exploration of an open field and reversal of some asymmetric visual behaviors (Barth et al., 2005; Facchin et al., 2009).

In addition to habenular and parapineal asymmetry being coordinated, we and others have shown that the parapineal organ is required for the development of L-R differences between the habenulae. When the parapineal organ is ablated or fails to form, both the left and right habenula develop with right-sided character (Concha et al., 2003; Gamse et al., 2003).

Although significant progress has been made to understand how an asymmetric epithalamus forms, many questions remain. How are parapineal neurons selected from a pool of pineal complex precursors, and directed to migrate to one side of the brain? How is neurogenesis in the habenular nuclei controlled, and how does the parapineal organ influence neurogenesis on the left side? How are the different characteristics of lateral versus medial habenular neurons formed?

In order to answer these questions, my laboratory is continuing to uncover the developmental events that lead to the formation of an asymmetric epithalamus. These include the specification, proliferation, migration, and differentiation events resulting in a left-sided parapineal organ and asymmetric habenular nuclei. We are using forward genetic screening and candidate approaches to identify the genes controlling epithalamic asymmetry, followed by in vivo analysis to understand how these genes influence neuronal development. Finally, we are starting to use behavioral assays to study the functional consequences of altering brain asymmetry. Ultimately, we would like to understand the fundamental principles that transform a symmetric nervous system into an asymmetric one.

Clanton, JA, Shestopalov, I, Chen, JK, Gamse, JT. Lineage labeling of zebrafish cells with laser uncagable fluorescein dextran. J Vis Exp(50), 2011 PMCID:3142468

Doll, CA, Burkart, JT, Hope, KD, Halpern, ME, Gamse, JT. Subnuclear development of the zebrafish habenular nuclei requires ER translocon function. Dev Biol, 360(1), 44-57, 2011

Taylor, RW, Qi, JY, Talaga, AK, Ma, TP, Pan, L, Bartholomew, CR, Klionsky, DJ, Moens, CB, Gamse, JT. Asymmetric inhibition of Ulk2 causes left-right differences in habenular neuropil formation. J Neurosci, 31(27), 9869-78, 2011 PMCID:3142468

de Borsetti, NH, Dean, BJ, Bain, EJ, Clanton, JA, Taylor, RW, Gamse, JT. Light and melatonin schedule neuronal differentiation in the habenular nuclei. Dev Biol, 358(1), 251-61, 2011

Taylor, RW, Hsieh, YW, Gamse, JT, Chuang, CF. Making a difference together: reciprocal interactions in C. elegans and zebrafish asymmetric neural development. Development, 137(5), 681-91, 2010 PMCID:2827681

Zhang, C, Song, Y, Thompson, DA, Madonna, MA, Millhauser, GL, Toro, S, Varga, Z, Westerfield, M, Gamse, J, Chen, W, Cone, RD. Pineal-specific agouti protein regulates teleost background adaptation. Proc Natl Acad Sci U S A, 107(47), 20164-71, 2010 PMCID:2996689

Alvarez-Delfin, K, Morris, AC, Snelson, CD, Gamse, JT, Gupta, T, Marlow, FL, Mullins, MC, Burgess, HA, Granato, M, Fadool, JM. Tbx2b is required for ultraviolet photoreceptor cell specification during zebrafish retinal development. Proc Natl Acad Sci U S A, 106(6), 2023-8, 2009 PMCID:2632714

Snelson, CD, Burkart, JT, Gamse, JT. Formation of the asymmetric pineal complex in zebrafish requires two independently acting transcription factors. Dev Dyn, 2008

Snelson, CD, Gamse, JT. Building an asymmetric brain: Development of the zebrafish epithalamus. Semin Cell Dev Biol, 2008 PMCID:2729063

Snelson, CD, Santhakumar, K, Halpern, ME, Gamse, JT. Tbx2b is required for the development of the parapineal organ. Development, 135(9), 1693-702, 2008

Kuan, YS, Gamse, JT, Schreiber, AM, Halpern, ME. Selective asymmetry in a conserved forebrain to midbrain projection. J Exp Zoolog B Mol Dev Evol, 308(5), 669-78, 2007

Pineda, RH, Svoboda, KR, Wright, MA, Taylor, AD, Novak, AE, Gamse, JT, Eisen, JS, Ribera, AB. Knockdown of Nav1.6a Na+ channels affects zebrafish motoneuron development. Development, 133(19), 3827-36, 2006

Tropepe, V, Li, S, Dickinson, A, Gamse, JT, Sive, HL. Identification of a BMP inhibitor-responsive promoter module required for expression of the early neural gene zic1. Dev Biol, 289(2), 517-29, 2006

Gamse, JT, Kuan, YS, Macurak, M, Brosamle, C, Thisse, B, Thisse, C, Halpern, ME. Directional asymmetry of the zebrafish epithalamus guides dorsoventral innervation of the midbrain target. Development, 132(21), 4869-81, 2005

Gamse, J T, Thisse, C, Thisse, B, Halpern, M E. The parapineal mediates left-right asymmetry in the zebrafish diencephalon. Development, 130(6), 1059-68, 2003

Halpern, M E, Liang, J O, Gamse, J T. Leaning to the left: laterality in the zebrafish forebrain. Trends Neurosci, 26(6), 308-13, 2003

Gamse, J T, Shen, Y-C, Thisse, C, Thisse, B , Raymond, P A, Halpern, M E, Liang, J O. Otx5 regulates genes that show circadian expression in the zebrafish pineal complex. Nat Genet, 30(1), 117-21, 2002

Gamse, J T, Sive, H. Early anteroposterior division of the presumptive neurectoderm in Xenopus. Mech Dev, 104(1-2), 21-36, 2001

Gamse, J, Sive, H. Vertebrate anteroposterior patterning: the Xenopus neurectoderm as a paradigm. Bioessays, 22(11), 976-86, 2000

Grinblat, Y, Gamse, J, Patel, M, Sive, H. Determination of the zebrafish forebrain: induction and patterning. Development, 125(22), 4403-16, 1998

Kuo, J S, Patel, M, Gamse, J, Merzdorf, C, Liu, X, Apekin, V, Sive, H. Opl: a zinc finger protein that regulates neural determination and patterning in Xenopus. Development, 125(15), 2867-82, 1998

Postdoctoral Position Available

Postdoctoral Position Details

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