5260B Biochemical Sciences Building
440 Henry Mall
Madison, WI 53706
Phone: (608) 262-9452
• B.S. 1982, Purdue University
• Ph.D. 1989, University of Wisconsin
• Postdoctoral 1990-1992, University of Wisconsin (M. Wickens)
• Postdoctoral 1992-1996, University of California, Berkeley (J. Gerhart)
• American Cancer Society Fellow, 1995
• March of Dimes Basil O'Connor Scholar, 1997
• Pew Scholar, 1998
• Beckman Young Investigator Award, 1998
Post-transcriptional control of vertebrate development. In all animals, temporally and spatially regulated post-transcriptional events direct development during the first hours following fertilization. These post-transcriptional events regulate the expression and/or the activity of maternally derived determinant proteins that control embryonic cell-fate decisions. Our studies of Xenopus laevis embryos have revealed that the expression and activity of specific maternal determinants are regulated by mechanisms that control the translation of maternal mRNAs (McGivern et al 2008, Zhang and Sheets 2009a, and Zhang et al, 2009b) and mechanisms that control the phosphorylation of determinant proteins (McGivern et al 2009).
Regulated mRNA translation is an important mechanism for regulating early cell-fate decisions in vertebrate embryos. Embryonic cells destined to specific fates accumulate distinct determinant proteins encoded by maternal mRNAs. These determinant proteins often function in cell-signaling pathways that direct the activation of select genes in only certain embryonic cells. For embryonic development to proceed normally, the expression of maternal determinants must be tightly controlled both temporally and spatially.
The Xenopus xCR1 protein is a receptor of the nodal signaling pathway, and vertebrate development requires the precise activation of this pathway at a specific time and place during embryogenesis. This requirement is met by restricting the accumulation of xCR1 protein to the animal cells within the developing embryo through the regulated translation of the maternal xCR1 mRNA (Zhang and Sheets, 2009). The maternal xCR1 mRNA is translated in animal cells while the xCR1 mRNA in vegetal cells is translationally repressed. The functional unit of mRNA translation is the mRNP that consists of the relevant mRNA regulatory sequences associated with specific RNA binding proteins. We have defined the mRNP that mediates repression in vegetal cells as consisting of the xCR1 mRNA's 3' UTR associated with the Pumilio and CUG-BP1 proteins (Zhang and Sheets, 2009). We are currently focused on understanding the mechanisms by which the xCR1 mRNP represses translation in one cell type but not the other. These mechanisms are key to understanding not only the spatially regulated translation of the xCR1 mRNA, but how such translational events control the earliest cell fate decisions made during vertebrate development.
Perform a customized PubMed literature search for Dr. Sheets.
• Zhang Y, Park S, Blaser S, Sheets MD. Determinants of RNA binding and
translational repression by the Bicaudal-C regulatory protein. J Biol Chem. 2014
Mar 14;289(11):7497-504. doi: 10.1074/jbc.M113.526426. Epub 2014 Jan 29. PubMed
PMID: 24478311; PubMed Central PMCID: PMC3953263.
• Zhang Y, Cooke A, Park S, Dewey CN, Wickens M, Sheets MD. Bicaudal-C spatially
controls translation of vertebrate maternal mRNAs. RNA. 2013 Nov;19(11):1575-82.
doi: 10.1261/rna.041665.113. Epub 2013 Sep 23. PubMed PMID: 24062572; PubMed
Central PMCID: PMC3851724.
• Reid CD, Zhang Y, Sheets MD, Kessler DS. Transcriptional integration of Wnt
and Nodal pathways in establishment of the Spemann organizer. Dev Biol. 2012 Aug
15;368(2):231-41. doi: 10.1016/j.ydbio.2012.05.018. Epub 2012 May 22. PubMed
PMID: 22627292; PubMed Central PMCID: PMC3572767.
• Friend K, Brook M, Bezirci FB, Sheets MD, Gray NK, Seli E. Embryonic
poly(A)-binding protein (ePAB) phosphorylation is required for Xenopus oocyte
maturation. Biochem J. 2012 Jul 1;445(1):93-100. doi: 10.1042/BJ20120304. PubMed
PMID: 22497250; PubMed Central PMCID: PMC3955212.
• Lund E, Sheets MD, Imboden SB, Dahlberg JE. Limiting Ago protein restricts
RNAi and microRNA biogenesis during early development in Xenopus laevis. Genes
Dev. 2011 Jun 1;25(11):1121-31. doi: 10.1101/gad.2038811. Epub 2011 May 16.
PubMed PMID: 21576259; PubMed Central PMCID: PMC3110951.
• Gorgoni B, Richardson WA, Burgess HM, Anderson RC, Wilkie GS, Gautier P,
Martins JP, Brook M, Sheets MD, Gray NK. Poly(A)-binding proteins are
functionally distinct and have essential roles during vertebrate development.
Proc Natl Acad Sci U S A. 2011 May 10;108(19):7844-9. doi:
10.1073/pnas.1017664108. Epub 2011 Apr 25. PubMed PMID: 21518916; PubMed Central
• Sheets MD, Fritz B, Hartley RS, Zhang Y. Polyribosome analysis for
investigating mRNA translation in Xenopus oocytes, eggs and embryos. Methods.
2010 May;51(1):152-6. doi: 10.1016/j.ymeth.2010.01.023. Epub 2010 Jan 22. PubMed
PMID: 20096782; PubMed Central PMCID: PMC2868116.
• Lund E, Liu M, Hartley RS, Sheets MD, Dahlberg JE. Deadenylation of maternal
mRNAs mediated by miR-427 in Xenopus laevis embryos. RNA. 2009
Dec;15(12):2351-63. doi: 10.1261/rna.1882009. Epub 2009 Oct 23. PubMed PMID:
19854872; PubMed Central PMCID: PMC2779678.
• McGivern JV, Swaney DL, Coon JJ, Sheets MD. Toward defining the
phosphoproteome of Xenopus laevis embryos. Dev Dyn. 2009 Jun;238(6):1433-43. doi:
10.1002/dvdy.21941. PubMed PMID: 19384857; PubMed Central PMCID: PMC2865133.
• Zhang Y, Forinash KD, McGivern J, Fritz B, Dorey K, Sheets MD. Spatially
restricted translation of the xCR1 mRNA in Xenopus embryos. Mol Cell Biol. 2009
Jul;29(13):3791-802. doi: 10.1128/MCB.01865-08. Epub 2009 Apr 13. PubMed PMID:
19364820; PubMed Central PMCID: PMC2698763.
• Zhang Y, Sheets MD. Analyses of zebrafish and Xenopus oocyte maturation
reveal conserved and diverged features of translational regulation of maternal
cyclin B1 mRNA. BMC Dev Biol. 2009 Jan 28;9:7. doi: 10.1186/1471-213X-9-7. PubMed
PMID: 19175933; PubMed Central PMCID: PMC2644680.
• Song J, McGivern JV, Nichols KW, Markley JL, Sheets MD. Structural basis for
RNA recognition by a type II poly(A)-binding protein. Proc Natl Acad Sci U S A.
2008 Oct 7;105(40):15317-22. doi: 10.1073/pnas.0801274105. Epub 2008 Sep 29.
PubMed PMID: 18824697; PubMed Central PMCID: PMC2563106.
• Mitchell T, Jones EA, Weeks DL, Sheets MD. Chordin affects pronephros
development in Xenopus embryos by anteriorizing presomitic mesoderm. Dev Dyn.
2007 Jan;236(1):251-61. PubMed PMID: 17106888; PubMed Central PMCID: PMC2094051.
• Lane MC, Sheets MD. Heading in a new direction: implications of the revised
fate map for understanding Xenopus laevis development. Dev Biol. 2006 Aug
1;296(1):12-28. Epub 2006 Apr 21. Review. PubMed PMID: 16750823.
• Constance Lane M, Davidson L, Sheets MD. BMP antagonism by Spemann's
organizer regulates rostral-caudal fate of mesoderm. Dev Biol. 2004 Nov
15;275(2):356-74. PubMed PMID: 15501224.