Faculty and Staff Directory

Centre for Cellular & Molecular Biology, Hyderabad, India Ph.D

Research in evolutionary developmental biology is directed at analyzing vertebrate homeobox gene function. These genes play important roles in the specification of positional identity along the embryonic axis. A major research effort is to identify regulatory mechanisms controlling developmental expression of the patterning genes and to compare such regulatory components whose divergence in related organisms correlates with divergent morphologies. These questions can be separated into three parts: (i) what are the cis- acting regulatory sequences of patterning genes that govern their developmental expressions? (ii) what are the trans- acting factors that interact with these cis- regulatory elements to establish the precise spatial and temporal pattern of gene expression? and (iii) which of these cis- and trans- acting components show variations in their sequence, expression and regulatory activities among vertebrates? These questions are readily addressed using molecular, biochemical and embryological techniques. This basic approach has several advantages. First, by establishing a causal relationship between a cis-acting element and a trans-acting factor, we can enumerate molecular interactions that define patterns generated in the developing embryo. Second, after isolating regulatory sequences with known spatial and temporal patterns of expression, we can use these elements to alter expression of other developmental regulatory molecules, thereby altering the normal course of development. Third, by documenting divergence among these regulatory components, we can determine both developmental and evolutionary mechanisms underlying patterning in diverse organisms.

Shashikant C.S., S.A. Bolanowski, S. Anand, and S.M. Anderson. Comparisons of diverged vertebrate Hoxc8 early enhancer activities reveal modification of regulatory interactions at conserved cis-acting elements. . J.Exp.Zool. Mol.Dev.Evol, 308, 242-249, 2007.

Bhat KM, N. Maddodi, C. Shashikant, and V. Setaluri. Transcriptional regulation of human MAP2 gene in melanoma: role of neuronal bHLH factors and Notch1 signaling. Nucleic Acids Res; 34:3819-3832, 2006.

Shashikant C., S.A. Bolanowski, J. Danke, and C.T. Amemiya. Hoxc8 early enhancer of the Indonesian coelacanth, Latimeria menadoensis. J.Exp.Zool. Mol.Dev.Evol. 302, 557-563, 2004.

Wang, C.H.W., S. Anand, D.R. Powell, A.B. Pawashe, C.T. Amimiya, and C.S. Shashikant. Comparative cis-regulatory analysis identify new elements of the mouse Hoxc8 early enhancer. J.Exp.Zool. Mol.Dev.Evol. 302, 436-445, 2004.

Gibbons, D., C. Shashikant, and A.C. Hayday. A comparative analysis of RNA targeting strategies in the thymosin beta 4 gene. J.Mol.Biol. 342, 1069-1076, 2004.

Shin, D., S.Korada, R. Raballo, C. Shashikant, A. Simeone, J. Taylor, and F. Vaccarino. Loss of glutamaergic pyramidal neurons in frontal and temporal cortex due to attenuation of FGFR1 signaling is associated with spontaneous hyperactivity in mice. J.Neuroscience, 24, 2247-2258, 2004.

Force A, C. Shashikant, P. Stadler, and C.T. Amemiya. Comparative genomics, cis-regulatory elements and gene duplication. Methods Cell Biol. 77: 545-561, 2004.

Anand, S., W.C.H. Wang, D.R Powell, S.A. Bolanowski, J. Zhang, C. Ledje, A.B. Pawashe, C.T. Amemiya, and C.S. Shashikant. Divergence of Hoxc8 early enhancer parallels diverged axial morphologies between mammals and fishes. Proc. Natl. Acad. Sci. (USA) 100, 15666-15669, 2003.

Kim C.B., C.S. Shashikant, W.C.H. Wang, K. Sumiyama, C.T. Amemiya, and F.H. Ruddle. Phylogenetic analysis of the mammalian Hoxc8 non-coding region. J. Struct. Functional Genomics. 3, 195-199, 2003.

Shashikant C.S. and Ruddle F.H. Impact of transgenic technologies on functional genomics. Curr Issues Mol Biol. 5, 75-98, 2003.

Sumiyama, K., S.Q. Irvine, D.W. Stock, K.M. Weiss, K. Kawasaki, N. Shimizu, C.S. Shashikant, W. Miller, and F.H. Ruddle. Genomic structure and functional control of the Dlx3-7 bigene cluster. Proc.Natl.Acad.Sci.(USA)99:780-785, 2002

Chiu-C-H., C. T. Amemiya, J. L. Carr, J. K. Hwang, J. Bhargava, C. S. Shashikant, F. H. Ruddle, and G. P. Wagner. A recombinogenic targeting method to modify large-inserts for cis-regulatory analysis in transgenic mice: construction and expression of a 100 kb, zf Hoxa-11b-lacZ reporter gene. Development Genes Evol., 210, 105-109, 2000.

Bhargava, J., C. S. Shashikant, J. L. Carr, K. L. Bentley, and F. H. Ruddle. Direct cloning of genomic DNA by recombinogenic targeting method using a yeast-bacteria shuttle vector, pClasper. Genomics, 62, 285-288, 1999.

Bhargava, J., C. S. Shashikant, J. L. Carr, K. L. Bentley, C. T. Amemiya, and F. H. Ruddle. pPAC-ResQ: a yeast-bacterial shuttle vector for capturing inserts from P1 and PAC clones by recombinogenic targeted cloning. Genomics, 56, 337-339, 1999.

Hanson, R. D., J. L. Hess, B. D. Yu, P. Ernst, M. van Lohuizen, C. S. Shashikant, F. H. Ruddle, M. Seto, and S. L. Korsmeyer. Mammalian trithorax and polycomb-group homologues are antagonistic regulators of homeotic development. Proc. Natl. Acad. Sci. (USA). 96, 14372-14377, 1999.

Igarashi, P., C. S. Shashikant, R. B. Thomson, D. A. Whyte, S. Liu-Chen, F. H. Ruddle, and P. S. Aronson. Ksp-cadherin gene promoter. II. Kidney –specific activity in transgenic mice. Am. J. Physiol. (Renal Physiol.). 277, F599-F610, 1999.

Ruddle, F. H., J. L. Carr, C. B. Kim, C. Ledje, C. S. Shashikant, and G. P. Wagner. Evolution of Hox gene clusters. N.Y. Acad. Sci. 870, 238-248, 1999.

Shashikant, C. S., J. L. Carr, J. Bhargava, K. L. Bentley, and F. H. Ruddle. Recombinogenic targeting: A new approach to genomic analysis- a review. Gene, 223, 9-20, 1998.

Shashikant, C. S., C. B. Kim, M. A. Borbeley, W. C. H. Wang, and F. H. Ruddle. Comparative studies on mammalian Hoxc8 early enhancer sequences reveal a baleen whale-specific deletion of a cis-acting sequence. Proc. Natl. Acad. Sci. (USA), 95, 15446-15451, 1998.

Belting, H.-G., C. S. Shashikant, and F. H. Ruddle. Multiple phases of expression and regulation of mouse Hoxc8 during early embryogenesis. J. Exp. Zool., 282, 196-222, 1998.

Belting, H-G., C. S. Shashikant, and F. H. Ruddle. Modification of expression and cis-regulation of Hoxc8 in the evolution of diverged axial morphology. Proc. Natl. Acad. Sci. USA, 95, 2355-2360, 1998.

Carr, J. L., C. S. Shashikant, W.J. Bailey, and F. H. Ruddle, Molecular evolution of Hox gene regulation: cloning and transgenic analysis of the lamprey HoxQ8 gene J. Exp. Zool., 280, 73-85, 1998.

Weiss, K., D. Stock, Z. Zhao, A. Buchanan, F. H. Ruddle, and C. S. Shashikant. Some perspectives on genetic aspects of dental patterning. European J. Oral Sciences, 106, 56-63, 1998.

Shashikant, C. S. and F. H. Ruddle. Combinations of closely situated cis-acting elements determine tissue-specific patterns and anterior extent of early Hoxc8 expression. Proc. Natl. Acad. Sci. USA 93: 12364-12369, 1996.

Bradshaw, M. S., C. S. Shashikant, H.-G. Belting, J. A. Bollekens, and F. H. Ruddle. A long range regulatory element of Hoxc-8 identified using the pClasper vector. Proc. Natl. Acad. Sci. USA 93: 2426-2430, 1996.

Lu, S., C. S. Shashikant, and F. H. Ruddle. Separate Cis-acting elements determine the expression of mouse Dbx gene in multiple spatial domains of the central nervous system. Mech. Dev., 58, 193-202, 1996.

Becker, D., Z. Jiang, P. Knodler, A. Deinhard R. Eid, K. Kidd, C. S. Shashikant, F. Ruddle, and K. Schughart. Conserved regulatory element involved in the early onset of Hoxb-6 gene expression. Dev. Dynamics 205: 73-81, 1996.

Shashikant, C. S., C. J. Bieberich, H.-G. Belting, J. C. H. Wang, M. A. Borbely, and F. H. Ruddle. Regulation of Hoxc-8 during mouse embryonic development: Identification and characterization of critical elements involved in early neural tube expression. Development 121: 4339-4347, 1995.

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