Associate Professor & Associate Head for Academic Affairs
Biological Sciences Building West
Biological Sciences Building West
Joined the Department in 2003
- B.S., 1981, University of California, Davis, Environmental Toxicology.
- Ph.D., 1989, University of Wisconsin, Madison, Bacteriology.
- Postdoctoral research, Princeton University and University of California, Berkeley.
Sex Determination and Threshold Responses in Development
Alternative developmental fates are often determined by small differences in the concentrations of signaling molecules. In many cases, cells respond to these signals within narrowly defined temporal windows and are unresponsive to the same signal molecules at other times in development. A number of aspects of Drosophila sex determination make it an ideal experimental system to study how strict temporal controls and small quantitative differences in protein concentration can elicit different developmental fates.
Sex is determined in Drosophila by the number of X chromosomes, with one X specifying male development and two specifying female. The dose of X chromosomes controls sex determination through its effects on the establishment promoter, SxlPe, of the regulatory gene Sex-lethal. Female development occurs as a consequence of Sxl being turned on in diplo-X animals while male development occurs in haplo-X animals because Sxl is left inactive. Although Sxl protein is required at all times to direct female differentiation, X chromosome dose affects Sxl expres ion only during a 30-40 min period in the pre-cellular embryo. After this time, Pe shuts off and Sxlis transcribed from a maintenance promoter, Pm, that operates in both sexes.
Genetic experiments have identified five elements on the X chromosome whose relative dose (one vs. two) is used to determine sex. These include the genes sisterlessA and -B, -C, runt, as well as Sxl itself. The sisA sisB and runt genes encode transcriptional activators of the bZIP, bHLH, and runt/AML class. The dose of these “counted” elements is measured with respect to a number of maternal and zygotically expressed proteins, some of which function as activators and some as inhibitors. We are studying the molecular interactions between the positively acting and inhibitory protein factors and their SxlPe promoter target. Our approach combines biochemistry with classical and molecular genetic analyses to identify novel molecules, and to characterize the protein/protein and protein/DNA interactions that regulate SxlPe. Given the ability to identify the key regulatory molecules, to study their expression, and to manipulate their levels and activity, in vitro, and in vivo; studies on Drosophila sex determination should prove ideal for understanding how transcriptional regulators of different classes can cooperate to generate sharp threshold responses.
- Mahadeveraju, S, Jung, YH, Erickson, JW. Evidence That Runt Acts as a Counter-Repressor of Groucho During Drosophila melanogaster Primary Sex Determination. G3 (Bethesda). 2020;10 (7):2487-2496. doi: 10.1534/g3.120.401384. PubMed PMID:32457096 PubMed Central PMC7341146.
- Mateos, M, Silva, NO, Ramirez, P, Higareda-Alvear, VM, Aramayo, R, Erickson, JW et al.. Effect of heritable symbionts on maternally-derived embryo transcripts. Sci Rep. 2019;9 (1):8847. doi: 10.1038/s41598-019-45371-0. PubMed PMID:31222094 PubMed Central PMC6586653.
- Erickson, JW. Primary Sex Determination in Drosophila melanogaster Does Not Rely on the Male-Specific Lethal Complex. Genetics. 2016;202 (2):541-9. doi: 10.1534/genetics.115.182931. PubMed PMID:26614741 PubMed Central PMC4788234.
- Salz, HK, Erickson, JW. Sex determination in Drosophila: The view from the top. Fly (Austin). 2010;4 (1):60-70. doi: 10.4161/fly.4.1.11277. PubMed PMID:20160499 PubMed Central PMC2855772.
- González, AN, Lu, H, Erickson, JW. A shared enhancer controls a temporal switch between promoters during Drosophila primary sex determination. Proc Natl Acad Sci U S A. 2008;105 (47):18436-41. doi: 10.1073/pnas.0805993105. PubMed PMID:19011108 PubMed Central PMC2587594.
- Lu, H, Kozhina, E, Mahadevaraju, S, Yang, D, Avila, FW, Erickson, JW et al.. Maternal Groucho and bHLH repressors amplify the dose-sensitive X chromosome signal in Drosophila sex determination. Dev Biol. 2008;323 (2):248-60. doi: 10.1016/j.ydbio.2008.08.012. PubMed PMID:18773886 PubMed Central PMC2653429.
- Erickson, JW, Quintero, JJ. Indirect effects of ploidy suggest X chromosome dose, not the X:A ratio, signals sex in Drosophila. PLoS Biol. 2007;5 (12):e332. doi: 10.1371/journal.pbio.0050332. PubMed PMID:18162044 PubMed Central PMC2222971.
- Avila, FW, Erickson, JW. Drosophila JAK/STAT pathway reveals distinct initiation and reinforcement steps in early transcription of Sxl. Curr Biol. 2007;17 (7):643-8. doi: 10.1016/j.cub.2007.02.038. PubMed PMID:17363251 .
- Möller, A, Avila, FW, Erickson, JW, Jäckle, H. Drosophila BAP60 is an essential component of the Brahma complex, required for gene activation and repression. J Mol Biol. 2005;352 (2):329-37. doi: 10.1016/j.jmb.2005.07.009. PubMed PMID:16083904 .
- Yang, D, Lu, H, Hong, Y, Jinks, TM, Estes, PA, Erickson, JW et al.. Interpretation of X chromosome dose at Sex-lethal requires non-E-box sites for the basic helix-loop-helix proteins SISB and daughterless. Mol Cell Biol. 2001;21 (5):1581-92. doi: 10.1128/MCB.21.5.1581-1592.2001. PubMed PMID:11238895 PubMed Central PMC86704.