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In memoriam: Susan Abmayr (1956–2019) – “What do we do? Whatever it takes!”
Skeletal Muscle volume 9, Article number: 29 (2019)
We are saddened to announce that Susan Abmayr, noted pioneer in Drosophila myogenesis, passed away suddenly on Thursday, July 18, 2019. Susan was born on March 13, 1956 in Pittsburgh, PA. She obtained her bachelor’s degree in Biological Sciences and Economics from Carnegie Mellon University in 1978 and completed her graduate training in 1987 under the mentorship of Robert G. Roeder, Ph.D. at Rockefeller University studying basic mechanisms of transcription. During her time in the Roeder lab, Susan met her husband and longtime collaborator, Jerry Workman, Ph.D. She performed her postdoctoral work with Tom Maniatis, Ph.D. in the Department of Biochemistry and Molecular Biology at Harvard University. Susan started her independent research career in the Department of Biochemistry and Molecular Biology at Penn State University and was promoted to Associate Professor in 1998. In 2003, Susan moved to the Stowers Institute for Medical Research in Kansas City as an Associate Investigator. She received a secondary appointment at the University of Kansas School of Medicine in 2004.
Susan’s contributions to the fields of transcription and myogenesis resulted in over 70 publications. Her scientific career and introduction to Drosophila as a model organism began in Sarah C. R. Elgin’s laboratory at Harvard University where she worked as a technician before starting graduate school. It was in the Elgin lab where Susan became familiar with chromatin organization and gene expression and forged life-long connections with fellow Elgin lab members [1,2,3]. Once in graduate school, she continued to pursue research questions related to transcription in the Roeder lab, with an emphasis on understanding transcriptional initiation by TFIID binding to promoter sequences [4,5,6,7].
Supported by a Damon Runyon-Walter Winchell Cancer Research Fund Post-Doctoral fellowship in the Maniatis lab, Susan was at the forefront in establishing Drosophila as a myogenic model. Only very few labs, among them Michael Bate’s lab in Cambridge UK, were using Drosophila to study muscle development at that time . Susan sought to bring her expertise in transcription to the fly. In 1989, Harold Weintraub’s group reported the isolation of mouse MyoD, a master regulatory gene for myogenic determination . When injected into non-muscle cell types, such as melanoma, neuroblastoma, liver, and adipocytes, MyoD transformed them into muscle. Capitalizing on the relative simplicity and ease of fly genetics, Susan merged her background in transcription with fly biology to uncover a Drosophila homolog of MyoD. In collaboration with her colleague Alan Michelson, they used the helix-loop-helix (HLH) regions of mouse MyoD and rat Myogenin as hybridization probes to screen a Drosophila genomic library. The identification of this fly MyoD protein, dubbed ‘Nautilus’ after the weight machine at the gym , broke open the embryonic myogenesis field in Drosophila and subsequently paved the way for the discovery of vertebrate Myocyte-specific Enhancer Factor 2, or Mef2 by Susan and other labs [11,12,13,14,15,16]. The absence of Mef2 results in a lack of muscle tissue. Without differentiation of naïve embryonic cells into myoblasts in these mutant embryos, the development of muscles fails.
At a time when the central focus of Drosophila studies was either on patterning the embryonic epidermis or on the establishment of the nervous system [17, 18], the advantages of using this stage of development to understand myogenesis became readily apparent. Muscle cell fate specification, myoblast fusion, myotube guidance, and attachment all occur in the relatively short time frame of ~ 10 h [19,20,21,22,23]. Moreover, the genetic tools and numerous reagents to follow individual proteins both in fixed and live tissue have allowed for a detailed dissection of myogenic events that are not possible in cell culture or mammalian models. One great example of exploiting this model system has been the use of genetic screens to identify molecules essential for myoblast fusion, which has been much of the focus of Susan’s research career.
The myogenesis field was mammalian focused in the late 1980s and early 1990s. Drosophila as an experimental system to study myogenesis was considered somewhat on the fringe at this time, yet this gave Susan a unique niche when she started her independent laboratory at Penn State University. Susan’s early years could best be classified as the years of discovery. While trying to make mutations in nautilus, Susan’s lab identified two genes required for the fusion of myoblasts to generate multinucleated myofibers. The first was sticks and stones (sns) which encodes for a transmembrane protein that is part of the immunoglobulin (Ig) superfamily . Sns is present on the surface of the fusion competent myoblasts (FCMs) [24, 25]. There it interacts at the sites of fusion with the Ig domain family member Dumbfounded (Duf) which is present on founder cells (FCs), or seed myoblasts, that give rise to an eventual syncytial muscle cell [25, 26]. Embryos that lack Sns have an abundance of unfused myoblasts that fail to form the stereotypical, multinucleated myofibers present in wild-type embryos [24, 27, 28]. The second gene uncovered was myoblast city (mbc) . The Mbc protein is a cytoplasmic protein that functions with the GTPase Rac to regulate the actin cytoskeleton. A quote from Susan in a 1994 Penn State publication  noted the novelty of her approach, “Not many people have looked at developing muscle in a fly embryo. We’re some of the first people in the country to start identifying these kinds of genetic defects.”
Susan’s foresight to use the fly system to identify conserved factors required for myogenesis quickly drew others to the field which resulted in the initiation of multiple genetic screens in other labs to uncover novel fusion mutants [31,32,33,34]. It was around this time in 2003 when Susan and Jerry moved their labs to the Stowers Institute. A major focus of the lab continued to be the identification of new players required in muscle development using the state-of-the-art technologies that Susan was so willing to incorporate. Expansion into proteomic approaches identified Elmo/Ced-12 as an obligate binding partner of Mbc to modulate actin cytoskeletal activity at the site of fusion . More importantly, the discovery of these early genes transitioned the field into characterizing the cellular events that govern the myoblast fusion process. This transition also brought with it Susan’s development of timelapse imaging approaches that were being pioneered in the field . Current models derived from the work in Susan’s lab and others show that FCMs must migrate and adhere to existing FCs. Cell adhesion mediated by Sns in the FCM and Duf in the FC relay signaling information through the MBC-ELMO-Rac pathway to mediate actin dynamics. Actin foci formation is dependent on the Formin, Diaphanous and, most notably, the Arp2/3 complex, which nucleates and drives actin-based polymerization [37,38,39,40,41,42]. The transient F-actin foci that is formed and resolved at the site of each membrane fusion event is accompanied by protrusions that induce membrane destabilization, pore formation, and ultimately fusion of the opposing lipid bilayers [43, 44]. Notably, many of the genes discovered in the Drosophila system by Susan and other fly labs have been later proven to be required for the fusion of vertebrate muscles .
Beyond her research achievements, Susan was well respected for her contributions in the Drosophila and myogenesis communities. She acted as the Heartland representative on the Drosophila Board, served as a grant reviewer for the National Institutes of Health (NIH) and the National Science Foundation (NSF), and helped organize a Frontiers in Myogenesis meeting in 2006. Susan defined what it meant to be an educator at many levels. At the forefront of her priorities was the training of graduate students. She was a passionate lecturer and a firm believer in the power and rigor of genetic approaches. After moving the lab from Penn State to the Stowers Institute, she was actively involved in graduate student recruiting and admissions through the University of Kansas Medical School (KUMC) graduate program for over 14 years. Susan’s mentoring also extended beyond her students: for example, she was an invaluable colleague on study panels, offering advice and counselling to new panel members on how to navigate the proper grant review.
Susan’s first love of transcription never wavered as she maintained a long-standing collaboration in the chromatin field with her husband, Jerry Workman. Her expertise in Drosophila genetics added an innovative angle to Jerry’s work that culminated in over 35 co-authored papers, primarily understanding the tissue-specific roles of Spt-Ada-Gcn5-acetyltransferase (SAGA) complexes during development. Outside of the lab, Susan and Jerry enjoyed extensive traveling and visiting with family. She also loved gardening, audiobooks, and Billy Holliday music. A late passion was volunteering through Uplift, a Kansas City based organization devoted to serving the homeless.
Every mentor, even subconsciously, instills scientific traits in their trainees that become ingrained and get passed onto future generations of researchers. Two words that embodied Susan’s approach to science were ‘rigor’ and ‘persistence.’ Expectations required accuracy and precision. Repetition assured both. It was rare for a project to be put on the sidelines. Every piece of information would eventually make sense with more experimentation. She would frequently wait in the lab until late in the evening to see the latest scientific result and never wavered in her commitment to student success, whether that be assisting with additional studying to pass a Ph.D. qualifying exam or making numerous revisions on a Ph.D. thesis. She will be missed by friends, colleagues, and the numerous trainees she mentored.
Howard GC, Abmayr SM, Shinefeld LA, Sato VL, Elgin SC. Monoclonal antibodies against a specific nonhistone chromosomal protein of Drosophila associated with active genes. J Cell Biol. 1981;88:219–25.
Cartwright IL, Abmayr SM, Fleischmann G, Lowenhaupt K, Elgin SC, Keene MA, Howard GC. Chromatin structure and gene activity: the role of nonhistone chromosomal proteins. CRC Crit Rev Biochem. 1982;13:1–86.
Hill RJ, Mott MR, Burnett EJ, Abmayr SM, Lowenhaupt K, Elgin SC. Nucleosome repeat structure is present in native salivary chromosomes of Drosophila melanogaster. J Cell Biol. 1982;95:262–6.
Abmayr SM, Feldman LD, Roeder RG. In vitro stimulation of specific RNA polymerase II-mediated transcription by the pseudorabies virus immediate early protein. Cell. 1985;43:821–9.
Abmayr SM, Workman JL, Roeder RG. The pseudorabies immediate early protein stimulates in vitro transcription by facilitating TFIID: promoter interactions. Genes Dev. 1988;2:542–53.
Workman JL, Abmayr SM, Cromlish WA, Roeder RG. Transcriptional regulation by the immediate early protein of pseudorabies virus during in vitro nucleosome assembly. Cell. 1988;55:211–9.
Cromlish WA, Abmayr SM, Workman JL, Horikoshi M, Roeder RG. Transcriptionally active immediate-early protein of pseudorabies virus binds to specific sites on class II gene promoters. J Virol. 1989;63:1869–76.
Bate M. The embryonic development of larval muscles in Drosophila. Development. 1990;110:791–804.
Weintraub H, Tapscott SJ, Davis RL, Thayer MJ, Adam MA, Lassar AB, Miller AD. Activation of muscle-specific genes in pigment, nerve, fat, liver, and fibroblast cell lines by forced expression of MyoD. Proc Natl Acad Sci U S A. 1989;86:5434–8.
Michelson AM, Abmayr SM, Bate M, Arias AM, Maniatis T. Expression of a MyoD family member prefigures muscle pattern in Drosophila embryos. Genes Dev. 1990;4:2086–97.
Paterson BM, Walldorf U, Eldridge J, Dübendorfer A, Frasch M, Gehring WJ. The Drosophila homologue of vertebrate myogenic-determination genes encodes a transiently expressed nuclear protein marking primary myogenic cells. Proc Natl Acad Sci U S A. 1991;88:3782–6.
Lilly B, Galewsky S, Firulli AB, Schulz RA, Olson EN. D-MEF2: a MADS box transcription factor expressed in differentiating mesoderm and muscle cell lineages during Drosophila embryogenesis. Proc Natl Acad Sci U S A. 1994;91:5662–6.
Nguyen HT, Bodmer R, Abmayr SM, McDermott JC, Spoerel NA. D-mef2: a Drosophila mesoderm-specific MADS box-containing gene with a biphasic expression profile during embryogenesis. Proc Natl Acad Sci U S A. 1994;91:7520–4.
Bour BA, O'Brien MA, Lockwood WL, Goldstein ES, Bodmer R, Taghert PH, Abmayr SM, Nguyen HT. Drosophila MEF2, a transcription factor that is essential for myogenesis. Genes Dev. 1995;9:730–41.
Lilly B, Zhao B, Ranganayakulu G, Paterson BM, Schulz RA, Olson EN. Requirement of MADS domain transcription factor D-MEF2 for muscle formation in Drosophila. Science. 1995;267:688–93.
Taylor MV, Beatty KE, Hunter HK, Baylies MK. Drosophila MEF2 is regulated by twist and is expressed in both the primordia and differentiated cells of the embryonic somatic, visceral and heart musculature. Mech Dev. 1995;50:29–41.
Campos-Ortega JA. Mechanisms of a cellular decision during embryonic development of Drosophila melanogaster: epidermogenesis or neurogenesis. Adv Genet. 1990;27:403–53.
Campos-Ortega JA. Cellular interactions in the developing nervous system of Drosophila. Cell. 1994;77:969–75.
Schejter ED, Baylies MK. Born to run: creating the muscle fiber. Curr Opin Cell Biol. 2010;22:566–74.
Schulman VK, Dobi KC, Baylies MK. Morphogenesis of the somatic musculature in Drosophila melanogaster. Wiley Interdiscip Rev Dev Biol. 2015;4:313–34.
Abmayr SM, Zhuang S, Geisbrecht ER. Myoblast fusion in Drosophila. Methods Mol Biol. 2008;475:75–97.
Haralalka S, Abmayr SM. Myoblast fusion in Drosophila. Exp Cell Res. 2010;316:3007–13.
Abmayr SM, Pavlath GK. Myoblast fusion: lessons from flies and mice. Development. 2012;139:641–56.
Bour BA, Chakravarti M, West JM, Abmayr SM. Drosophila SNS, a member of the immunoglobulin superfamily that is essential for myoblast fusion. Genes Dev. 2000;14:1498–511.
Galletta BJ, Chakravarti M, Banerjee R, Abmayr SM. SNS: adhesive properties, localization requirements and ectodomain dependence in S2 cells and embryonic myoblasts. Mech Dev. 2004;121:1455–68.
Ruiz-Gómez M, Coutts N, Price A, Taylor MV, Bate M. Drosophila dumbfounded: a myoblast attractant essential for fusion. Cell. 2000;102:189–98.
Kocherlakota KS, Wu JM, McDermott J, Abmayr SM. Analysis of the cell adhesion molecule sticks-and-stones reveals multiple redundant functional domains, protein-interaction motifs and phosphorylated tyrosines that direct myoblast fusion in Drosophila melanogaster. Genetics. 2008;178:1371–83.
Shelton C, Kocherlakota KS, Zhuang S, Abmayr SM. The immunoglobulin superfamily member Hbs functions redundantly with Sns in interactions between founder and fusion-competent myoblasts. Development. 2009;136:1159–68.
Erickson MR, Galletta BJ, Abmayr SM. Drosophila myoblast city encodes a conserved protein that is essential for myoblast fusion, dorsal closure, and cytoskeletal organization. J Cell Biol. 1997;138:589–603.
Marino G. Making a Muscle. 1994. (news.pus.edu).
Paululat A, Burchard S, Renkawitz-Pohl R. Fusion from myoblasts to myotubes is dependent on the rolling stone gene (rost) of Drosophila. Development. 1995;121:2611–20.
Schäfer G, Weber S, Holz A, Bogdan S, Schumacher S, Müller A, Renkawitz-Pohl R, Onel SF. The Wiskott-Aldrich syndrome protein (WASP) is essential for myoblast fusion in Drosophila. Dev Biol. 2007;304:664–74.
Chen EH, Olson EN. Antisocial, an intracellular adaptor protein, is required for myoblast fusion in Drosophila. Dev Cell. 2001;1:705–15.
Chen EH, Pryce BA, Tzeng JA, Gonzalez GA, Olson EN. Control of myoblast fusion by a guanine nucleotide exchange factor, loner, and its effector ARF6. Cell. 2003;114:751–62.
Geisbrecht ER, Haralalka S, Swanson SK, Florens L, Washburn MP, Abmayr SM. Drosophila ELMO/CED-12 interacts with myoblast city to direct myoblast fusion and ommatidial organization. Dev Biol. 2008;314:137–49.
Haralalka S, Shelton C, Cartwright HN, Guo F, Trimble R, Kumar RP, Abmayr SM. Live imaging provides new insights on dynamic F-actin filopodia and differential endocytosis during myoblast fusion in Drosophila. PLoS One. 2014;9:e114126.
Kim S, Shilagardi K, Zhang S, Hong SN, Sens KL, Bo J, Gonzalez GA, Chen EH. A critical function for the actin cytoskeleton in targeted exocytosis of prefusion vesicles during myoblast fusion. Dev Cell. 2007;12:571–86.
Richardson BE, Beckett K, Nowak SJ, Baylies MK. SCAR/WAVE and Arp2/3 are crucial for cytoskeletal remodeling at the site of myoblast fusion. Development. 2007;134:4357–67.
Haralalka S, Shelton C, Cartwright HN, Katzfey E, Janzen E, Abmayr SM. Asymmetric Mbc, active Rac1 and F-actin foci in the fusion-competent myoblasts during myoblast fusion in Drosophila. Development. 2011;138:1551–62.
Hornbruch-Freitag C, Griemert B, Buttgereit D, Renkawitz-Pohl R. Drosophila Swiprosin-1/EFHD2 accumulates at the prefusion complex stage during Drosophila myoblast fusion. J Cell Sci. 2011;124:3266–78.
Kaipa BR, Shao H, Schäfer G, Trinkewitz T, Groth V, Liu J, Beck L, Bogdan S, Abmayr SM, Önel SF. Dock mediates Scar- and WASp-dependent actin polymerization through interaction with cell adhesion molecules in founder cells and fusion-competent myoblasts. J Cell Sci. 2013;126:360–72.
Bothe I, Deng S, Baylies M. PI (4,5) P2 regulates myoblast fusion through Arp2/3 regulator localization at the fusion site. Development. 2014;141:2289–301.
Sens KL, Zhang S, Jin P, Duan R, Zhang G, Luo F, Parachini L, Chen EH. An invasive podosome-like structure promotes fusion pore formation during myoblast fusion. J Cell Biol. 2010;191:1013–27.
Segal D, Dhanyasi N, Schejter ED, Shilo BZ. Adhesion and fusion of muscle cells are promoted by Filopodia. Dev Cell. 2016;38:291–304.
Vasyutina E, Martarelli B, Brakebusch C, Wende H, Birchmeier C. The small G-proteins Rac1 and Cdc42 are essential for myoblast fusion in the mouse. Proc Natl Acad Sci U S A. 2009;106:8935–40.
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Geisbrecht, E.R., Baylies, M.K. In memoriam: Susan Abmayr (1956–2019) – “What do we do? Whatever it takes!”. Skeletal Muscle 9, 29 (2019) doi:10.1186/s13395-019-0215-0