Genetics and Cell Biology, Organismal
Biology and Anatomy, Committee
on Development, Regeneration, and Stem Cell Biology, Committee on Genetics, Genomics & Systems Biology, Committee on Cancer Biology
SB, Computer Science/Biology, M.I.T., 1976
PhD, M.I.T. and Woods Hole Oceanographic Inst., 1985
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 original focus of the lab was
on the role of the Bone Morphogenetic Protein family member Decapentaplegic
(Dpp) in patterning the D/V axis. In the past, we demonstrated that
the system that patterns the embryonic D/V axis is conserved between
arthropods and chordates, identified the mechanism by which the
Spemann organizer patterns the Xenopus body axis, and characterized
essential and modulatory components of the Dpp signal transduction
Recently, we showed that, although
Dpp is broadly transcribed dorsally, receptor-bound Dpp is only
observed in a sharp stripe comprising the dorsal-most cells. We
demonstrated that formation of this pattern of Dpp – receptor
interactions involves two distinct processes. First, Dpp undergoes
long-range extracellular movement facilitated by the Dpp-binding
protein Sog. Second, an intracellular positive feedback circuit
promotes Dpp - receptor interactions as a function of previous signaling
strength. The two processes cooperate to produce the observed spatial
bistability of Dpp-receptor interactions.
We have also begun to investigate
processes underlying maintenance of the germ line stem cells (GSCs)
in the adult ovary. Like most adult stem cells, the GSCs are present
in an environmental niche, which provides signals necessary for
their maintenance. Dpp is a niche signal required for GSC maintenance.
We hypothesize that interactions between the GSC and the surrounding
niche cells create an intrinsic polarity in the GSC. This polarity
both controls the plane of GSC division and elevates responsiveness
to Dpp within the GSC. These two characteristics ensure a robust
pattern of asymmetric, self-renewal divisions.
Page, B. D., Diede, S. J., Tenlen
J. R. and Ferguson, E. L. (2007). "EEL-1, a Hect E3 ubiquitin
ligase, controls asymmetry and persistence of the SKN-1 transcription
factor in the early C. elegans embryo. " Development 134: 2303-2314.
Wang, Y.-C. and Ferguson, E.L. (2005).
"Spatial bistability of Dpp-receptor interactions during Drosophila
dorsal-ventral patterning." Nature, 434: 229-234. (PubMed)
Casanueva, M. O. and Ferguson, E.
L. (2004). "Germline stem cell number in the Drosophila ovary
is regulated by redundant mechanisms that control Dpp signaling."
Development 131: 1881-90. (PubMed)
Podos, S. D., Hanson, K. K., Wang,
Y. C. and Ferguson, E. L. (2001). "The DSmurf ubiquitin-protein
ligase restricts BMP signaling spatially and temporally during Drosophila
embryogenesis." Developmental Cell 1: 567-78. (PubMed)
Decotto, E. and Ferguson, E. L. (2001).
"A positive role for Short gastrulation in modulating BMP signaling
during dorsoventral patterning in the Drosophila embryo." Development
128: 3831-41. (PubMed)
Neul, J. L., and Ferguson, E. L.
(1998). Spatially-restricted activation of the SAX receptor by SCW
modulates DPP/TKV signaling in Drosophila dorsal-ventral patterning.
Cell 95: 483-494. (PubMed)
Holley, S. A., Neul, J. L., Attisano,
L., Wrana, J. L., Sasai, Y., O'Connor, M. B., De Robertis, E. M.
and Ferguson, E. L. (1996). "The Xenopus dorsalizing factor
noggin ventralizes Drosophila embryos by preventing DPP from activating
its receptor." Cell 86: 607-17. (PubMed)
Holley, S. A., Jackson, P. D., Sasai,
Y., Lu, B., De Robertis, E. M., Hoffmann, F. M. and Ferguson, E.
L. (1995). "A conserved system for dorsal-ventral patterning
in insects and vertebrates involving sog and chordin." Nature
376: 249-53. (PubMed)