ZFIN ID: ZDB-LAB-990226-1
Chandrasekhar Lab
PI/Director: Chandrasekhar, Anand
Contact Person: Chandrasekhar, Anand
Email: anandc@missouri.edu
URL: https://chandrasekhar.biology.missouri.edu/
Address: Division of Biological Sciences University of Missouri 344 Bond Life Sciences Center 1201 Rollins Street Columbia, MO 65211 USA
Country: United States
Phone: (573) 882-5192
Fax: (573) 884-9676
Line Designation: zou


GENOMIC FEATURES ORIGINATING FROM THIS LAB
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STATEMENT OF RESEARCH INTERESTS
Neuronal Migration in the Vertebrate Brain

The long-term goal of our research is to understand the mechanisms that mediate neuronal migration in mammals. In the vertebrate embryo, neurons frequently migrate long distances to reach their final positions, where they assemble into complex networks that control physiology and behavior. Many human neurological disorders result when neurons either migrate aberrantly or fail to migrate. Therefore, it is essential to understand the mechanisms mediating migration of specific neuronal types, so that the causes of and potential remedies for human brain disorders can eventually be identified. Our studies may also impact efforts to induce stem cell-derived neurons to migrate accurately into brain regions damaged by injury or disease.
Our lab employs the migration of facial branchiomotor neurons (FBMNs) in the zebrafish and mouse hindbrain as a model for neuronal migrations in mammals. The FBMNs are a subset of cranial motor neurons found in the vertebrate brainstem. In mammals, the FBMNs compose the motor component of cranial nerve VII, and innervate muscles of facial expression, and of the middle ear and upper neck.
Currently, our work is focused on elucidating the roles of components of the Wnt/Planar Cell Polarity pathway in regulating the directionality and extent of FBMN migration. These studies are performed in zebrafish and mice, using experimental approaches that each model system is uniquely suited for, such as time-lapse imaging and conditional gene knockout.
We showed previously that tangential migration of facial branchiomotor neurons (FBMNs) is completely eliminated in the zebrafish gastrulation mutant trilobite. The trilobite locus encodes Vangl2, a four-pass transmembrane protein that is a component of the non-canonical Wnt/Planar Cell Polarity (Wnt/PCP) pathway. Vangl2 is expressed in FBMNs and surrounding tissues during the period of FBMN migration. Three major lines of investigation in the lab are:

Structure-function analysis of zebrafish Vangl2 protein (Dr. Pan)
While the C-terminal cytoplasmic region of Vangl2 is necessary for mediating gastrulation-associated movements, the roles of the N-terminal cytoplasmic region and of the extracellular loops have not been examined. We are generating transgenic lines expressing variant forms of the Vangl2 protein to test their abilities to rescue the FBMN migration defect of trilobite mutants. These studies will define the regions of Vangl2 (and the molecular interactions they participate in) involved in neuronal migration.

Cellular site of Vangl2 function (Dr. Sittaramane)
We showed previously that vangl2 functions non-cell autonomously (i.e., outside motor neurons) for FBMN migration. We are performing targeted cell transplants to examine whether vangl2 functions in specific cell types such as mesoderm and floorplate to regulate FBMN migration.

Role of Wnt/PCP genes in FBMN migration in mice (Mr. Glasco)
Our zebrafish work and other studies have shown that non-canonical Wnt/PCP pathway components play essential roles in mediating FBMN migration. Furthermore, many of these molecules function non-cell autonomously to regulate FBMN migration, suggesting that novel signaling mechanisms may be involved. We are examining the extent to which these functions are evolutionarily conserved by testing whether these molecules also have essential functions during FBMN migration in mammals (i.e., mice).


Other Projects:
- Analysis of the role of integrin signaling in FBMN migration.
- Reverse genetic screen for genes regulating neuronal development in the zebrafish hindbrain.
- Analysis of roles of the Gbx transcription factors in motor neuron development.
- Establishment of an in vitro (cell culture) system using human cancer cells to study the roles of Wnt/PCP components in migration.
- Analysis of the effects of endocrine disruptors on zebrafish development.


LAB MEMBERS
Pan, Xiufang Post-Doc Sittaramane, Vinoth Post-Doc Baccam, Chiengkham Fish Facility Staff


ZEBRAFISH PUBLICATIONS OF LAB MEMBERS
Ferguson, R., Holloway, D.E., Chandrasekhar, A., Acharya, K.R., Subramanian, V. (2019) The catalytic activity and secretion of zebrafish RNases are essential for their in vivo function in motor neurons and vasculature. Scientific Reports. 9:1107
Wen, X.Y., Tarailo-Graovac, M., Brand-Arzamendi, K., Willems, A., Rakic, B., Huijben, K., Da Silva, A., Pan, X., El-Rass, S., Ng, R., Selby, K., Philip, A.M., Yun, J., Ye, X.C., Ross, C.J., Lehman, A.M., Zijlstra, F., Bakar, A.A., Drögemöller, B., Moreland, J., Wasserman, W.W., Vallance, H., van Scherpenzeel, M., Karbassi, F., Hoskings, M., Engelke, U., de Brouwer, A., Wevers, R.A., Pshezhetsky, A.V., van Karnebeek, C.D., Lefeber, D.J. (2018) Sialic acid catabolism by N-acetylneuraminate pyruvate lyase is essential for muscle function. JCI insight. 3(24):
Gurung, S., Asante, E., Hummel, D., Williams, A., Feldman-Schultz, O., Halloran, M.C., Sittaramane, V., Chandrasekhar, A. (2018) Distinct roles for the cell adhesion molecule Contactin2 in the development and function of neural circuits in zebrafish. Mechanisms of Development. 152:1-12
Allen, J.R., Bhattacharyya, K.D., Asante, E., Almadi, B., Schafer, K., Davis, J., Cox, J., Voigt, M., Viator, J.A., Chandrasekhar, A. (2017) Role of branchiomotor neurons in controlling food intake of zebrafish larvae. Journal of neurogenetics. 31(3):128-137
Chandrasekhar, A., Guo, S., Masai, I., Nicolson, T., Wu, C.F. (2017) Zebrafish: from genes and neurons to circuits, behavior and disease. Journal of neurogenetics. 31:59-60
Sittaramane, V., Padgett, J., Salter, P., Williams, A., Luke, S., McCall, R., Arambula, J.F., Graves, V.B., Blocker, M., Van Leuven, D., Bowe, K., Heimberger, J., Cade, H.C., Immaneni, S., Shaikh, A. (2015) Discovery of Quinoline-Derived Trifluoromethyl Alcohols, Determination of Their in vivo Toxicity and Anticancer Activity in a Zebrafish Embryo Model. ChemMedChem. 10(11):1802-7
Roszko, I., Sepich, D., Jessen, J.R., Chandrasekhar, A., Solnica-Krezel, L. (2015) A dynamic intracellular distribution of Vangl2 accompanies cell polarization during zebrafish gastrulation. Development (Cambridge, England). 142(14):2508-20
Heimberger, J., Cade, H.C., Padgett, J., Sittaramane, V., Shaikh, A. (2015) Total synthesis of Herbarin A and B, determination of their antioxidant properties and toxicity in zebrafish embryo model. Bioorganic & medicinal chemistry letters. 25(6):1192-5
Pan, X., Sittaramane, V., Gurung, S., and Chandrasekhar, A. (2014) Structural and temporal requirements of Wnt/PCP protein Vangl2 function for convergence and extension movements and facial branchiomotor neuron migration in zebrafish. Mechanisms of Development. 131:1-14
Sittaramane, V., Pan, X., Glasco, D.M., Huang, P., Gurung, S., Bock, A., Li, S., Wang, H., Kawakami, K., Matise, M.P., and Chandrasekhar, A. (2013) The PCP protein Vangl2 regulates migration of hindbrain motor neurons by acting in floor plate cells, and independently of cilia function. Developmental Biology. 382(2):400-412
Glasco, D.M., Sittaramane, V., Bryant, W., Fritzsch, B., Sawant, A., Paudyal, A., Stewart, M., Andre, P., Cadete Vilhais-Neto, G., Yang, Y., Song, M.R., Murdoch, J.N., and Chandrasekhar, A. (2012) The mouse Wnt/PCP protein Vangl2 is necessary for migration of facial branchiomotor neurons, and functions independently of Dishevelled. Developmental Biology. 369(20):211-222
Burroughs-Garcia, J., Sittaramane, V., Chandrasekhar, A., and Waters, S.T. (2011) Evolutionarily conserved function of Gbx2 in anterior hindbrain development. Developmental dynamics : an official publication of the American Association of Anatomists. 240(4):828-838
Bouvrette, D.J., Sittaramane, V., Heidel, J.R., Chandrasekhar, A., and Bryda, E.C. (2010) Knockdown of bicaudal C in zebrafish (Danio rerio) causes cystic kidneys: a nonmammalian model of polycystic kidney disease. Comparative medicine. 60(2):96-106
Bingham, S.M., Sittaramane, V., Mapp, O., Patil, S., Prince, V.E., and Chandrasekhar, A. (2010) Multiple mechanisms mediate motor neuron migration in the zebrafish hindbrain. Developmental Neurobiology. 70(2):87-99
Sittaramane, V., Sawant, A., Wolman, M.A., Maves, L., Halloran, M.C., and Chandrasekhar, A. (2009) The cell adhesion molecule Tag1, transmembrane protein Stbm/Vangl2, and Lamininalpha1 exhibit genetic interactions during migration of facial branchiomotor neurons in zebrafish. Developmental Biology. 325(2):363-373
Sawant, A. (2009) Cellular behaviors regulating tangential migration of facial branchiomotor neurons in the zebrafish embryo. Master's Thesis. :68p
Korzh, S., Pan, X., Garcia-Lecea, M., Winata, C.L., Pan, X., Wohland, T., Korzh, V., and Gong, Z. (2008) Requirement of vasculogenesis and blood circulation in late stages of liver growth in zebrafish. BMC Developmental Biology. 8(1):84
Pan, X., Zhan, H., and Gong, Z. (2008) Ornamental Expression of Red Fluorescent Protein in Transgenic Founders of White Skirt Tetra (Gymnocorymbus ternetzi). Marine biotechnology (New York, N.Y.). 10(5):497-501
Maeda, Y., Suzuki, T., Pan, X., Chen, G., Pan, S., Bartman, T., and Whitsett, J.A. (2008) Cul2 is required for the activity of hypoxia-inducible factor and vasculogenesis. The Journal of biological chemistry. 283(23):16084-16092
Farooq, M., Sulochana, K.N., Pan, X., To, J., Sheng, D., Gong, Z., and Ge, R. (2008) Histone deacetylase 3 (hdac3) is specifically required for liver development in zebrafish. Developmental Biology. 317(1):336-353
Wolman, M.A., Sittaramane, V., Essner, J.J., Yost, H.J., Chandrasekhar, A., and Halloran, M.C. (2008) Transient axonal glycoprotein-1 (TAG-1) and laminin-alpha1 regulate dynamic growth cone behaviors and initial axon direction in vivo. Neural Development. 3:6
Sittaramane, V., and Chandrasekhar, A. (2008) Expression of unconventional myosin genes during neuronal development in zebrafish. Gene expression patterns : GEP. 8(3):161-170
Wu, Y.L., Pan, X., Mudumana, S.P., Wang, H., Kee, P.W., and Gong, Z. (2008) Development of a heat shock inducible gfp transgenic zebrafish line by using the zebrafish hsp27 promoter. Gene. 408(1-2):85-94
Dong, P.D., Munson, C.A., Norton, W., Crosnier, C., Pan, X., Gong, Z., Neumann, C.J., and Stainier, D.Y. (2007) Fgf10 regulates hepatopancreatic ductal system patterning and differentiation. Nature Genetics. 39(3):397-402
Bingham, S.M., Toussaint, G., and Chandrasekhar, A. (2005) Neuronal development and migration in zebrafish hindbrain explants. Journal of Neuroscience Methods. 149(1):42-49
Mukhi, S., Pan, X., Cobb, G.P., and Patino, R. (2005) Toxicity of hexahydro-1,3,5-trinitro-1,3,5-triazine to larval zebrafish (Danio rerio). Chemosphere. 61(2):178-185
Vanderlaan, G., Tyurina, O.V., Karlstrom, R.O., and Chandrasekhar, A. (2005) Gli function is essential for motor neuron induction in zebrafish. Developmental Biology. 282(2):550-570
Pan, X., Wan, H., Chia, W., Tong, Y., and Gong, Z. (2005) Demonstration of site-directed recombination in transgenic zebrafish using the Cre/loxP system. Transgenic Research. 14(2):217-223
Teraoka, H., Russell, C., Regan, J., Chandrasekhar, A., Concha, M.L., Yokoyama, R., Higashi, K., Take-Uchi, M., Dong, W., Hiraga, T., Holder, N., and Wilson, S.W. (2004) Hedgehog and Fgf signaling pathways regulate the development of tphR-expressing serotonergic raphe neurons in zebrafish embryos. Journal of neurobiology. 60(3):275-288
Chandrasekhar, A. (2004) Turning heads: development of vertebrate branchiomotor neurons. Developmental dynamics : an official publication of the American Association of Anatomists. 229(1):143-161
Bingham, S., Chaudhari, S., Vanderlaan, G., Itoh, M., Chitnis, A., and Chandrasekhar, A. (2003) Neurogenic phenotype of mind bomb mutants leads to severe patterning defects in the zebrafish hindbrain. Developmental dynamics : an official publication of the American Association of Anatomists. 228(3):451-463
Jessen, J.R., Topczewski, J., Bingham, S., Sepich, D.S., Marlow, F., Chandrasekhar, A., and Solnica-Krezel, L. (2002) Zebrafish trilobite identifies new roles for Strabismus in gastrulation and neuronal movements. Nature cell biology. 4(8):610-615
Bingham, S., Higashijima, S.-I., Okamoto, H., and Chandrasekhar, A. (2002) The zebrafish trilobite gene is essential for tangential migration of branchiomotor neurons. Developmental Biology. 242(2):149-160
Bingham, S., Nasevicius, A., Ekker, S.C., and Chandrasekhar, A. (2001) Sonic hedgehog and tiggy-winkle hedgehog cooperatively induce zebrafish branchiomotor neurons. Genesis (New York, N.Y. : 2000). 30(3):170-174
Chandrasekhar, A., Schauerte, H.E., Haffter, P., and Kuwada, J.Y. (1999) The zebrafish detour gene is essential for cranial but not spinal motor neuron induction. Development (Cambridge, England). 126(12):2727-2737
Yee, C.S., Chandrasekhar, A., Halloran, M.C., Shoji, W., Warren, J.T., and Kuwada, J.Y. (1999) Molecular cloning, expression, and activity of zebrafish semaphorin Z1a. Brain research bulletin. 48(6):581-593
Warren, J.T., Jr., Chandrasekhar, A., Kanki, J.P., Rangarajan, R., Furley, A.J., and Kuwada, J.Y. (1999) Molecular cloning and developmental expression of a zebrafish axonal glycoprotein similar to TAG-1. Mechanisms of Development. 80(2):197-201
Chandrasekhar, A., Warren, Jr., J.T., Takahashi, K., Schauerte, H.E., van Eeden, F.J.M., Haffter, Pl, and Kuwada, J.Y. (1998) Role of sonic hedgehog in branchiomotor neuron induction in zebrafish. Mechanisms of Development. 76:101-115
Chandrasekhar, A., Moens, C.B., Warren, J.T., Kimmel, C.B., and Kuwada, J.Y. (1997) Development of branchiomotor neurons in zebrafish. Development (Cambridge, England). 124(13):2633-2644