Edwin L. Ferguson

Research Summary
The lab approaches questions of pattern formation and cell fate specification in the fruit fly Drosophila melanogaster. Our current interests are the mechanisms underlying the patterning of the embryonic dorsal-ventral (D/V) axis and the asymmetric self-renewal divisions of adult stem cells. The main focus of lab has been on the role of the Bone Morphogenetic Protein (BMP) family member Decapentaplegic (Dpp) in patterning the D/V axis. Over the years, my laboratory discovered the conservation of dorsal-ventral patterning mechanisms between arthropods and chordates, identified the function of the Spemann organizer in Xenopus, showed that a non-linear feedback circuit resulted in a bistable pattern of BMP signaling during Drosophila D/V patterning, identified a genetic network that confers robustness to the D/V patterning system in Drosophila, and was involved in a collaboration to demonstrate that spatial-temporal changes in the BMP gradient drove morphological changes during Dipteran evolution. We have also investigated the processes responsible for the maintenance of the germ line stem cells (GSCs) in the adult ovary. The GSCs are present in a niche composed of non-dividing somatic cells, and these cells secrete BMP ligands necessary for GSC maintenance. The GSC has high levels of BMP signaling, while its sister cell, the Cystoblast, has low levels of BMP signaling and begins the process of differentiation. We have identified multiple redundant mechanisms that aid in creating this dichotomy in BMP signaling between sister cells. In particular, we have shown that interactions between the GSC and the surrounding niche cells create an intrinsic polarity in the GSC that both controls the plane of GSC division and elevates responsiveness to Dpp within the GSC. Recently, we have shown that GSCs can be maintained in the niche with very low levels of BMP signaling, which has implications for stem cell maintenance during aging.
Keywords
Pattern Formation, Embryogenesis, Intercellular Signaling, Stem Cell Biology, Development and Evolution, Drosophila
Education
  • Massachusetts Institute of Technology, B.S. Electrical Engineering 06/1976
  • B.S. Biology 06/1976
  • Woods Hole Oceanographic Institute &, Ph.D. Genetics 05/1985
  • Massachusetts Institute of Technology,
  • University of California, Berkeley, Postdoc Genetics 06/1992
Awards & Honors
  • 1987 - 1990 Helen Hay Whitney Postodctoral Fellowship
  • 1993 - 1997 Pew Scholar in the Biomedical Sciences
  • 2000 - 2001 Cancer Research Foundation Fletcher Scholar
  • 2008 - 2011 Senior Scholar Award in Aging, Ellison Medical Foundation
  • 2009 - Llewellyn John and Harriet Manchester Quantrell Award for Excellence in Undergraduate Teaching
  • 2011 - Biological Sciences Division Distinguished Educator and Mentor Award
Publications
  1. Kwan CW, Gavin-Smyth J, Ferguson EL, Schmidt-Ott U. Functional evolution of a morphogenetic gradient. Elife. 2016 12 22; 5. View in: PubMed

  2. Gavin-Smyth J, Ferguson EL. zen and the art of phenotypic maintenance: canalization of embryonic dorsal-ventral patterning in Drosophila. Fly (Austin). 2014; 8(3):170-5. View in: PubMed

  3. Gavin-Smyth J, Wang YC, Butler I, Ferguson EL. A genetic network conferring canalization to a bistable patterning system in Drosophila. Curr Biol. 2013 Nov 18; 23(22):2296-2302. View in: PubMed

  4. Lu W, Casanueva MO, Mahowald AP, Kato M, Lauterbach D, Ferguson EL. Niche-associated activation of rac promotes the asymmetric division of Drosophila female germline stem cells. PLoS Biol. 2012; 10(7):e1001357. View in: PubMed

  5. Goldstein JA, Kelly SM, LoPresti PP, Heydemann A, Earley JU, Ferguson EL, Wolf MJ, McNally EM. SMAD signaling drives heart and muscle dysfunction in a Drosophila model of muscular dystrophy. Hum Mol Genet. 2011 Mar 01; 20(5):894-904. View in: PubMed

  6. Yu H, Seah A, Herman MA, Ferguson EL, Horvitz HR, Sternberg PW. Wnt and EGF pathways act together to induce C. elegans male hook development. Dev Biol. 2009 Mar 15; 327(2):419-32. View in: PubMed

  7. Page BD, Diede SJ, Tenlen JR, Ferguson EL. EEL-1, a Hect E3 ubiquitin ligase, controls asymmetry and persistence of the SKN-1 transcription factor in the early C. elegans embryo. Development. 2007 Jun; 134(12):2303-14. View in: PubMed

  8. Wang YC, Ferguson EL. Spatial bistability of Dpp-receptor interactions during Drosophila dorsal-ventral patterning. Nature. 2005 Mar 10; 434(7030):229-34. View in: PubMed

  9. Casanueva MO, Ferguson EL. Germline stem cell number in the Drosophila ovary is regulated by redundant mechanisms that control Dpp signaling. Development. 2004 May; 131(9):1881-90. View in: PubMed

  10. Podos SD, Hanson KK, Wang YC, Ferguson EL. The DSmurf ubiquitin-protein ligase restricts BMP signaling spatially and temporally during Drosophila embryogenesis. Dev Cell. 2001 Oct; 1(4):567-78. View in: PubMed

  11. Decotto E, Ferguson EL. A positive role for Short gastrulation in modulating BMP signaling during dorsoventral patterning in the Drosophila embryo. Development. 2001 Oct; 128(19):3831-41. View in: PubMed

  12. Podos SD, Ferguson EL. Morphogen gradients: new insights from DPP. Trends Genet. 1999 Oct; 15(10):396-402. View in: PubMed

  13. Neul JL, Ferguson EL. Spatially restricted activation of the SAX receptor by SCW modulates DPP/TKV signaling in Drosophila dorsal-ventral patterning. Cell. 1998 Nov 13; 95(4):483-94. View in: PubMed

  14. Xu X, Yin Z, Hudson JB, Ferguson EL, Frasch M. Smad proteins act in combination with synergistic and antagonistic regulators to target Dpp responses to the Drosophila mesoderm. Genes Dev. 1998 Aug 01; 12(15):2354-70. View in: PubMed

  15. Hudson JB, Podos SD, Keith K, Simpson SL, Ferguson EL. The Drosophila Medea gene is required downstream of dpp and encodes a functional homolog of human Smad4. Development. 1998 Apr; 125(8):1407-20. View in: PubMed

  16. Tax FE, Thomas JH, Ferguson EL, Horvitz HR. Identification and characterization of genes that interact with lin-12 in Caenorhabditis elegans. Genetics. 1997 Dec; 147(4):1675-95. View in: PubMed

  17. Holley SA, Ferguson EL. Fish are like flies are like frogs: conservation of dorsal-ventral patterning mechanisms. Bioessays. 1997 Apr; 19(4):281-4. View in: PubMed

  18. Ferguson EL. Conservation of dorsal-ventral patterning in arthropods and chordates. Curr Opin Genet Dev. 1996 Aug; 6(4):424-31. View in: PubMed

  19. Holley SA, Neul JL, Attisano L, Wrana JL, Sasai Y, O'Connor MB, De Robertis EM, Ferguson EL. The Xenopus dorsalizing factor noggin ventralizes Drosophila embryos by preventing DPP from activating its receptor. Cell. 1996 Aug 23; 86(4):607-17. View in: PubMed

  20. Holley SA, Jackson PD, Sasai Y, Lu B, De Robertis EM, Hoffmann FM, Ferguson EL. A conserved system for dorsal-ventral patterning in insects and vertebrates involving sog and chordin. Nature. 1995 Jul 20; 376(6537):249-53. View in: PubMed

  21. Huang M, Gu G, Ferguson EL, Chalfie M. A stomatin-like protein necessary for mechanosensation in C. elegans. Nature. 1995 Nov 16; 378(6554):292-5. View in: PubMed

  22. Ferguson EL, Horvitz HR. Identification and characterization of 22 genes that affect the vulval cell lineages of the nematode Caenorhabditis elegans. Genetics. 1985 May; 110(1):17-72. View in: PubMed

  23. Ferguson EL, Sternberg PW, Horvitz HR. A genetic pathway for the specification of the vulval cell lineages of Caenorhabditis elegans. Nature. 1987 Mar 19-25; 326(6110):259-67. View in: PubMed

  24. Ferguson EL, Horvitz HR. The multivulva phenotype of certain Caenorhabditis elegans mutants results from defects in two functionally redundant pathways. Genetics. 1989 Sep; 123(1):109-21. View in: PubMed

  25. Shimell MJ, Ferguson EL, Childs SR, O'Connor MB. The Drosophila dorsal-ventral patterning gene tolloid is related to human bone morphogenetic protein 1. Cell. 1991 Nov 01; 67(3):469-81. View in: PubMed

  26. Ferguson EL, Anderson KV. Dorsal-ventral pattern formation in the Drosophila embryo: the role of zygotically active genes. Curr Top Dev Biol. 1991; 25:17-43. View in: PubMed

  27. Ferguson EL, Anderson KV. Localized enhancement and repression of the activity of the TGF-beta family member, decapentaplegic, is necessary for dorsal-ventral pattern formation in the Drosophila embryo. Development. 1992 Mar; 114(3):583-97. View in: PubMed

  28. Ferguson EL, Anderson KV. Decapentaplegic acts as a morphogen to organize dorsal-ventral pattern in the Drosophila embryo. Cell. 1992 Oct 30; 71(3):451-61. View in: PubMed

  29. Anderson KV, Schneider DS, Morisato D, Jin Y, Ferguson EL. Extracellular morphogens in Drosophila embryonic dorsal-ventral patterning. Cold Spring Harb Symp Quant Biol. 1992; 57:409-17. View in: PubMed