Huntington's disease research with Dictyostelium amoebae: Michael A. Myre, PhD, member of the Molecular Neurogenetics Unit at the Center for Human Genetic Research (CHGR).
Huntingtin regulation of prespore cell fate in Dictyostelium is cell-autonomous.
When starved, Dictyostelium amoebae produce, secrete and chemotax towards cAMP to form a bona fide multicellular organism within a period of 24 hours that consists of a ball of spores upheld on a slender stalk. (A) Depicted here is the cell type distribution and patterning that occurs during the slug stage of development (image modified from Mohanty and Firtel, Cell and Developmental Biology, 1999). Prestalk cells sort to front of slug whereas prespore cells comprise the posterior. Cell type distribution and proportioning is highly organized and fixed along an anterior-posterior axis with ~80% of the slug comprising the prespore domain. Many secreted morphogens serve as signals that regulate cell fate, motility and differentiation during this stage of development. (B) Wild-type and GFP-marked hd- cells GFP were mixed (e.g., 1:3 or less) with unmarked wild-type cells as indicated and cell fate was assessed. When GFP-labeled wild-type cells were mixed with the same genotype, cells were found distributed evenly throughout the slug (top panel); in contrast, GFP-labeled hd- cells failed to populate the prespore regions of the slug when mixed with unmarked wild-type cells (lower panel). (C) When GFP-labeled hd- cells were mixed with the same genotype as a control, no difference in cellular distribution was detected (top panel); in contrast, GFP-labeled wild-type cells failed to populate the prestalk regions of the slug when challenged with unmarked hd- cells (lower panel). Slugs are positioned with their indicated posterior prespore (psp) zones to the left and anterior prestalk (pst) zones to the right. Slug structures were developed on phosphate buffered agar and viewed by DIC and fluorescent microscopy. Results are representative of three independent experiments for all panels shown.
Contact Michael A. Myre
Michael A. Myre, PhD
Massachusetts General Hospital,
Center for Human Genetic Research
Simches Research Center, CPZN-5.612A
185 Cambridge St.
Boston, MA 02114