Robert M. Grainger
- AB, Stanford University
- PhD, University of California, Berkeley
- Postdoc, Yale University
- Professor, Biology
Molecular embryology--gene regulation in cells committed to specific developmental lineages
My laboratory is investigating how the axial properties of vertebrate embryos are first established and then how particular tissues are determined within defined regions of the embryo. Research projects concerning axis formation focus on how the anterior/posterior neural axis is established, and research regarding tissue determination centers on development of the eye. We are studying these developmental processes at two levels: first, trying to understand the tissue interactions that control these events, and then, to establish whether the action of particular regulatory genes is important in these early developmental decisions.
An analysis of axis formation was initiated because of our observations indicating that establishment of anterior/posterior axial properties in the nervous system (delineation of the brain from the spinal cord) is completed surprisingly late, some time after the initial stimulus activating formation of neural tissue. Experiments are underway to define the tissue interactions in the embryo that eventually lead to the orderly arrangement of neural tissues along the anterior/posterior axis.
Experiments on eye determination have concerned mainly the formation of the lens, which is formed in close association with the retina. The developing retina has long been thought to cause lens formation in overlying ectoderm by transmitting a signal to it. This is one of the classic examples of embryonic induction which has been studied intensively because the relative simplicity of the interaction between retina and lens allows it to be examined more carefully than the interactions leading to determination of many other tissues. Our recent work has helped to define more clearly the important tissue interactions required for lens formation and has led to a significantly revised view of how this process occurs. In addition to characterizing the tissue interactions leading to lens formation, studies are underway to determine the chemical signals involved in these interactions.
As a complement to these studies of tissue interactions we have examined gene activities that are likely to be responsible for some of these early axis- forming and tissue- determining events. Until the last few years very few genes had been identified that might be important in regulating establishment of such developmental properties in the embryonic head. We have now identified several genes likely to have such functions; they encode transcription factors that are expressed specifically in the anterior forebrain and eye tissues. Studies are presently underway to examine exactly how these genes may control important events of determination.
- Nakayama T, Fisher M, Nakajima K, Odeleye A, Zimmerman K, Fish M, Yaoita Y, Chojnowski J, Lauderdale J, Netland P, Grainger R. Xenopus pax6 mutants affect eye development and other organ systems, and have phenotypic similarities to human aniridia patients. Developmental biology. 2015. PMID: 25724657
- Fish M, Nakayama T, Fisher M, Hirsch N, Cox A, Reeder R, Carruthers S, Hall A, Stemple D, Grainger R. Xenopus mutant reveals necessity of rax for specifying the eye field which otherwise forms tissue with telencephalic and diencephalic character. Developmental biology. 2014. PMID: 25224223
- Nakayama T, Blitz I, Fish M, Odeleye A, Manohar S, Cho K, Grainger R. Cas9-based genome editing in Xenopus tropicalis. Methods in enzymology. 2014;546 355-75. PMID: 25398349 | PMCID: PMC4284096
- Xenopus tropicalis as a Model Organism for Genetics and Genomics: Past, Present, and Future. Methods in molecular biology (Clifton, N.J.). 2012;917 3-15. PMID: 22956079 | PMCID: PMC3918953
- Jin H, Fisher M, Grainger R. Defining progressive stages in the commitment process leading to embryonic lens formation. Genesis (New York, N.Y. : 2000). 2012;50(10): 728-40. PMID: 22566346 | PMCID: PMC3870160
- Wei S, Xu G, Bridges L, Williams P, Nakayama T, Shah A, Grainger R, White J, DeSimone D. Roles of ADAM13-regulated Wnt activity in early Xenopus eye development. Developmental biology. 2012;363(1): 147-54. PMID: 22227340 | PMCID: PMC3288294
- Fish M, Nakayama T, Grainger R. Simple, fast, tissue-specific bacterial artificial chromosome transgenesis in Xenopus. Genesis (New York, N.Y. : 2000). 2011;50(3): 307-15. PMID: 22084035 | PMCID: NIHMS343469
- Hellsten U, Harland R, Gilchrist M, Hendrix D, Jurka J, Kapitonov V, Ovcharenko I, Putnam N, Shu S, Taher L, Blitz I, Blumberg B, Dichmann D, Dubchak I, Amaya E, Detter J, Fletcher R, Gerhard D, Goodstein D, Graves T, Grigoriev I, Grimwood J, Kawashima T, Lindquist E, Lucas S, Mead P, Mitros T, Ogino H, Ohta Y, Poliakov A, Pollet N, Robert J, Salamov A, Sater A, Schmutz J, Terry A, Vize P, Warren W, Wells D, Wills A, Wilson R, Zimmerman L, Zorn A, Grainger R, Grammer T, Khokha M, Richardson P, Rokhsar D. The genome of the Western clawed frog Xenopus tropicalis. Science (New York, N.Y.). 2010;328(5978): 633-6. PMID: 20431018 | PMCID: PMC2994648
- Ogino H, Fisher M, Grainger R. Convergence of a head-field selector Otx2 and Notch signaling: a mechanism for lens specification. Development (Cambridge, England). 2007;135(2): 249-58. PMID: 18057103 | PMCID: PMC3918164
- Ogino H, McConnell W, Grainger R. High-throughput transgenesis in Xenopus using I-SceI meganuclease. Nature protocols. 2007;1(4): 1703-10. PMID: 17487153
- Ogino H, McConnell W, Grainger R. Highly efficient transgenesis in Xenopus tropicalis using I-SceI meganuclease. Mechanisms of development. 2006;123(2): 103-13. PMID: 16413175