Mark M. Voigt, Ph.D.

Professor and Vice Chairman
Pharmacological and Physiological Science


Research

The research in this lab is centered on the molecular and genetic basis of sensory signaling by the peripheral nervous system. We are using the developing zebrafish as our model system, which allows us to conduct studies in living, developing animals. By utilizing expression of transgenes in intact organisms, the appropriate tissue and cellular contexts are maintained in our studes. Sensory input from both the external and internal environments is essential for normal organismal function. The peripheral sensory neurons responsible for sensation in the head are present in ganglia known as the cranial sensory ganglia (CSG), which are associated with the cranial nerves. These neurons collect sensory information from peripheral tissues and relay this input to the central nervous system, where it can be integrated and processed so that the appropriate response is generated. The CSG are responsible for not only conveying general somatosensory input from particular regions of the head, but also special sensory information such as chemosensation, gustation and viscerosensory signals. Together, the CSG are responsible for relaying not only information relevant to pain and touch from the face and mouth, but also sensory input used to control movements of the jaw and pharynx during mastication and swallowing, gustation, the sensing of oxygenation and blood pressure in the carotid arteries and aortic arch, and mechanosensation in the visceral organs as well.

For the past number of years, our research efforts were focused on ATP, one of the neurotransmitters used by the CSG. Those studies centered on studies of a class of ATP-gated ion channels designated P2X receptors. More recently, the emphasis in the lab has shifted to investigating the molecular and genetic basis of sensory transmission by the peripheral sensory nervous system. Our group is focused on three basic questions concerning these neurons: first, how do the individual neurons establish their specific connections to the appropriate peripheral and central targets; second, what are the genes that determine the modality an individual neuron will transduce; and third, how is the sensory information they carry to the brain encoded ? To address these questions, the lab employs a combination of modern technologies that include molecular genetics, optical imaging and forward genetic screens.

We have identified the family of P2X receptor genes in the zebrafish, and have identified four members which are expressed selectively in sensory neurons in the developing fish. We have used these genes to produce constructs in which genetically-encoded fluorescent reporters, disruptor proteins, or transcriptional activators are expressed in cell-specific fashions. We have recently engineered a transgenic fish line in which all the neurons of the CSG (with the exception of the acoustic and lateral line ganglia) are labeled with eGFP. We are currently conducting a forward genetic screen using this line in order to identify genes that are involved in the formation and function of the peripheral sensory nervous system.

Figure 1 Fish Figure 1. A 200x confocal image of the head of a 77 hour post fertilization transgenic larva expressing eGFP under the control of the p2rx3.2 gene promoter . Note that both the cell bodies and processes of the cranial sensory ganglia are labeled by the reporter gene.
Figure 2 Fish Figure 2. A 400x confocal image of the sensory nerves from the cranial ganglia entering the hindbrain. Also seen are hindbrain interneurons expressing the transgene.
Figure 3 Fish Figure 3. A 100x image of a transgenic fish stained with an antibody against the adhesion molecule DM-GRASP (red). In this image, the cranial ganglia and their nerves, together with the Rohon-Beard neurons of the spinal cord, are labeled green, while the endoderm in the branchial arches, the motor neurons and nerves, commissural neurons in the hindbrain and various peripheral nerve bundles are labeled red.

Publications

Pope, H.M and Voigt, M.M. (2014) Peripheral glia have a pivotal role in the initial response to axon degeneration of peripheral sensory neurons in zebrafish. PLoS One 9(7):e103283. PMID: 25058656

Cox, J.A., LaMora, A., Johnson, S.L. and Voigt, M.M. (2014) Novel role for carbamoyl phosphate synthetase 2 in cranial circuit formation. Int’l J. Dev. Neurosci. 33:41-48.PMID:24280100

Chen, W.H, Tseng, W.F., Lin, G.H., Schreiner, A., Chen, H.R., Voigt, M.M., Yuh, C.H., Wu, J.L., Huang, S.S. and Huang, J.S. (2013) The ortholog of LYVE-1 Is Required for Thoracic Duct Development in Zebrafish. Cellbio 2:228-247.

Cox, J.A., LaMora, A., Johnson, S.L. and Voigt, M.M. Diverse mechanisms for assembly of branchiomeric nerves. Developmental Biology 2011 357(2):305-317. PMID: 21777575

Cox, J.A., McAdow, A.R., Dinitz, A.E., McCallion, A.S., Johnson, S.L. and Voigt, M.M. A zebrafish SKIV2L2-enhancer trap line provides a useful tool for the study of peripheral sensory circuit development. Gene Expression Patterns. 2011 Jul 1 [Epub ahead of print] PMID:21742057

Kucenas, S., Cox, J.A., Soto, F., LaMora, A. and Voigt, M.M. (2009) Ectodermal P2X receptor function plays a pivotal role in craniofacial development of the zebrafish. Purinergic Signaling 5:395-407.

LaMora, A. and Voigt, M.M. (2009) Cranial sensory ganglia neurons require intrinsic N-cadherin function for guidance of afferent fibers to their final targets. Neuroscience 159:1175-1184.

Kucenas, S., Soto, F., Cox, J.A. and Voigt, M.M. (2006) Selective labeling of sensory neurons in the developing zebrafish using P2X3 receptor subunit transgenes. Neuroscience 138:641-652.

Cox, J.A., Kucenas, S., and Voigt, M.M. (2005) Molecular characterization and embryonic expression of a family of genes encoding N-methyl-D-aspartate ionotropic receptor subunits in zebrafish. Dev. Dyn. 234:756-766.

Pratt, E. B., Brink, T. S., Bergson, P., Voigt, M.M. and Cook, S.P. (2005) Use-dependent inhibition of P2X3 receptors by nanomolar agonist. J. Neurosci. 25:7359-7365.

Li, Z., Migita, K., Samways, D.S.-K., Voigt, M.M. and Egan, T.M. (2004) Gain and loss of channel function by alanine-substitutions in the transmembrane segments of the rat ATP-gated P2X2 receptor. J. Neurosci. 24:9378-9386.

Egan, T.M., Cox, J.A. and Voigt, M.M. (2004) Molecular structure of P2X receptors. in Current Topics in Medicinal Chemistry 4(8):821-829 (Jacobsen, K., ed) Academic Press, San Diego, CA.

Kucenas, S., Li, Z.Y., Cox, J.A., Egan., T.M. and Voigt, M.M. (2003) Molecular cloning and characterization of the zebrafish P2X receptor subunit gene family Neuroscience 121:935-945.

Egan, T.M. and Voigt, M.M. (2003) Relating the structure of ATP-gated ion channel receptors to their function. in Current Topics in Membranes, 53:183-202 (Schwiebert, E.M., ed.). Academic Press, San Diego, CA.

Diaz-Hernandez, M., Cox, J.A., Migita, K., Haines, W.R., Egan, T.M. and Voigt, M.M. (2002) Cloning and characterization of two novel zebrafish P2X receptor subunits. Biochem. Biophys. Res. Comm. 295:849-853.

Khakh, B.S., Burnstock, G., Kennedy C., King, B.F., North, R.A., Seguela, P., Voigt, M. and P.P.A. Humphrey (2001) International Union of Pharmacology. XXIV. Current status of the nomenclature and properties of P2X receptors and their subunits. Pharmacol. Rev. 53:107-118.

Haines WR, Voigt MM, Migita K, Torres GE, Egan TM (2001) On the contribution of the first transmembrane domain to whole-cell current through an ATP-gated ionotropic P2X receptor. Journal of Neuroscience 21:5885-5892.

Haines WR, Migita K, Cox JA, Egan TM, Voigt MM (2001) The first transmembrane domain of the P2X receptor subunit participates in the agonist-induced gating of the channel. Journal of Biological Chemistry 276: 32793-32798.

Migita K, Haines WR, Voigt MM, Egan TM (2001) Polar residues of the second transmembrane domain influence cation permeability of the ATP-gated P2x2 receptor. Journal of Biological Chemistry 276:30934-30941.

Khakh,B.S., Barnard, E. A., Burnstock, G., Kennedy, C., King, B.F.,North, R.A., Séguéla, P.,Voigt, M. and P. P. A. Humphrey (2000) P2X Receptors. in The IUPHAR Compendium of Receptor Characterization and Classification.

Egan, T.M., Cox, J.A. and Voigt, M. (2000) Molecular Cloning and functional characterization of the zebrafish ATP-gated receptor P2X3 subunit. FEBS Letters 475:287-290.

Cox, J.A., Barmina, O. and Voigt, M.M. (2001) Gene structure, chromosomal localization, cDNA cloning and expression of the mouse ATP-gated ionotropic receptor P2X5 subunit. Gene: 270:145-152.

Haines, W.R., Torres, G.T., Voigt, M.M. & Egan, T.M., (1999) Properties of the novel ATP-gated ionotropic receptor composed of P2X1 and P2X5 isoforms. Molecular Pharmacology 56:720-727.

Torres, G., Egan, T.M. and Voigt, M.M. (1999) Identification of a domain involved in ATP-gated ionotropic P2X receptor subunit assembly. J. Biol. Chem. 274:22359-22365.

Torres, G., Egan, T.M. and Voigt, M.M. (1999) Hetero-oligomeric assembly of P2X receptor subunits: specificities exist with regard to possible partners. J. Biol. Chem.274:6653-6659.

Torres, G., Haines, W.R, Egan, T.M. and Voigt, M.M. (1998) Co-expression of the P2X1 and P2X5 receptor subunits reveals a novel ATP-gated ion channel. Mol. Pharmacol. 54:989-993.

Torres, G., Egan, T.M. and Voigt, M.M. (1998) N-linked glycosylation is essential for the functional expression of the recombinant P2X2 receptor. Biochemistry 37:14845-14851.

Torres, G., Egan, T.M. and Voigt, M.M.. (1998) Topological analysis of the ATP-gated ionotropic P2X2 receptor subunit. FEBS Lett. 425:19-23.

Egan, T., Haines, W. and Voigt, M.M. (1998) Identification of a domain contributing to the ion-conducting pore of the ATP-gated P2X2 receptors identified by the substituted cysteine accessibility method. J. Neurosci. 18:2350-2359.