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Abmayr Lab
Susan Abmayr, Ph.D.
Associate Investigator
sma@stowers.org
Abmayr Lab Research Website		 Postdoctoral position currently available.
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Organogenesis: Integration of cell-cell interactions and intracellular signaling cascades to generate differentiated tissues
     During the development of multicellular organisms, differentiating cells acquire specific properties and capabilities associated with their ultimate purpose in the body. In addition, different cell types must coordinate to organize themselves into functional structures. The fruit fly Drosophila melanogaster is an excellent model system to study organogenesis for many reasons, among them its rapid life cycle, the ability to utilize both classical genetics and transgenic approaches, and the variety of biochemical and cell biological methods that are available.

     Our research focuses primarily on the embryonic development of the larval body wall muscles, with a specific emphasis on the fusion of myoblasts into multinucleate muscle fibers. The multinucleate muscle fibers utilized by the larva are generated by fusion between two distinct populations of myoblasts. The first, termed founder myoblasts, are located in characteristic and reproducible positions in the embryo and contain information that specifies muscle identity, size, position, and attachment. These cells dictate the muscle pattern and seed the fusion process. The more populous fusion-competent myoblasts (FCMs) appear to be committed to myogenesis, but have no inherent fiber specificity. Recognition, migration, and adhesion between the founder cells and FCMs are critical prerequisites to myoblast fusion.

     We identified SNS, a cell adhesion molecule that is specifically expressed on the surface of the FCMs. SNS on the surface of the FCMs mediates interaction with similar cell adhesion molecules on the surface of the founder cells, and directs their subsequent fusion into muscle fibers. As observed for its vertebrate ortholog nephrin, SNS appears to sit at the top of one or more signal transduction cascades that impact the actin cytoskeleton. Among the cytoplasmic proteins that may function downstream of SNS, we have identified myoblast city (mbc). MBC was a founding member of the CDM superfamily which, along with MBC, includes C. elegans CED-5, human Dock180, is one component of a bipartite guanine nucleotide exchange factors for the small GTPase rac1. These CDM proteins function in a complex with the PH domain containing protein CED-12/ELMO to activate rac1 as an essential step in myoblast fusion. Of note, recent studies from other labs have indicated that this role for MBC has been conserved in vertebrate muscle. Current efforts are directed toward identifying novel components of this signaling pathway in Drosophila, and elucidating of their roles in myoblast fusion.

     A new area of research in our lab focuses on the Drosophila nephrocytes, cells that function throughout larval and adult life to remove molecules from the hemolymph, the open circulatory system of the insect. We noted molecular, morphological and functional similarities between these cells and the epithelial cells that surround the blood vessels in the vertebrate kidney. In particular, SNS is expressed on the surface of the nephrocyte, where it plays a critical role in plasma membrane interactions through which a slit-diaphragm-like structure is formed. Indeed, SNS is present at this nephrocyte diaphragm, which functions as a filter to control the size-dependent uptake of molecules into a series of labyrinthine channels for subsequent uptake by endocytosis. In a similar manner, the SNS ortholog nephrin is critical for formation of the kidney slit diaphragm, which mediates passage of molecules from the bloodstream into the urine. Moreover, like SNS in the insect nephrocyte diaphragm, nephrin is a structural component of the slit diaphragm. Current efforts are utilizing this insect model system to identify and better understand molecules downstream of SNS, with the hope that novel molecules will provide insight into kidney function.

Academic Appointment: Associate Professor, Department of Anatomy & Cell Biology, The University of Kansas School of Medicine

Selected publications

Zhuang S, Shao H, Guo F, Trimble R, Pearce E, Abmayr SM. Sns and Kirre, the Drosophila orthologs of Nephrin and Neph1, direct adhesion, fusion and formation of a slit diaphragm-like structure in insect nephrocytes. Development. 2009;136:2335-2344. Abstract

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;136:1159-1168. Abstract

Abmayr SM, Zhuang S, Geisbrecht ER. Myoblast fusion in Drosophila. Methods Mol Biol. 2008;475:75-97. Abstract

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;178:1371-1383. Abstract

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;314:137-149. Abstract

Balagopalan L, Chen MH, Geisbrecht ER, Abmayr SM. The CDM superfamily protein MBC directs myoblast f7usion through a mechanism that requires phosphatidylinositol 3,4,5-triphosphate binding but is independent of direct interaction with DCrk. Mol Cell Biol. 2006;26:9442-9455. Abstract

Guelman S, Suganuma T, Florens L, Weake V, Swanson SK, Washburn MP, Abmayr SM, Workman JL. The Essential Gene wda Encodes a WD40 Repeat Subunit of Drosophila SAGA Required for Histone H3 Acetylation. Mol Cell Biol. 2006;26:7178-7189. Abstract

Guelman S, Suganuma T, Florens L, Swanson SK, Kiesecker CL, Kusch T, Anderson S, Yates JR, 3rd, Washburn MP, Abmayr SM, Workman JL. Host cell factor and an uncharacterized SANT domain protein are stable components of ATAC, a novel dAda2A/dGcn5-containing histone acetyltransferase complex in Drosophila. Mol Cell Biol. 2006;26:871-882. Abstract

Abmayr SM, Kocherlakota KS. Muscle morphogenesis: the process of embryonic myoblast fusion. In: H Sink, ed. Muscle Development in Drosophila. Georgetown, Tex. New York, N.Y.: Landes Bioscience/Eurekah.com ;Springer Science+Business Media; 2006:p.1-12. Table of Contents

Abmayr SM, Balagopalan L, Galletta BJ, Hong S-J. Myogenesis and Muscle Development. In: L Gilbert, I K., and S Gill, eds. Comprehensive Molecular Insect Science. 1st ed. San Diego, CA: Pergamon; Elsevier LTD; ©2005;2:p. 1-45. Table of Contents

Kusch T, Florens L, Macdonald WH, Swanson SK, Glaser RL, Yates III JR, Abmayr SM, Washburn MP, Workman JL. Acetylation by Tip60 is required for selective histone variant exchange at DNA lesions. Science. 2004;306:2084-2087. Abstract

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;121:1455-1468. Abstract
 
Workman JL, Abmayr SM. Histone H3 variants and modifications on transcribed genes. Proc Natl Acad Sci U S A. 2004;101:1429-1430. Abstract

Abmayr SM, Workman JL. Transcription factors prominently in Lasker Award to Roeder. Cell. 2003;115:243-246. Abstract

Presgraves DC, Balagopalan L, Abmayr SM, Orr HA. Adaptive evolution drives divergence of a hybrid inviability gene between two species of Drosophila. Nature. 2003;423:715-719. Abstract.

Kusch T, Guelman S, Abmayr SM, Workman JL. Two Drosophila Ada2 homologues function in different multiprotein complexes. Mol Cell Biol. 2003;23:3305-3319. Abstract.

Abmayr SM, Balagopalan, L, Galletta BJ, Hong, S-J. Cell and molecular biology of myoblast fusion. Int'l Rev Cyt. 2003;225: 33-89. Abstract.

Balagopalan L, Keller CA, Abmayr SM.  Loss-of-function mutations reveal that the Drosophila nautilus gene is not essential for embryonic myogenesis or viability. Dev Biol. 2001;231:374-382. Abstract.

Bour BA, Chakravarti M, West J, Abmayr SM. Drosophila SNS, a member of the immunoglobulin superfamily that is essential for myoblast fusion. Genes Dev. 2000;14:1498-1511. Abstract.

Galletta BJ, Niu X-P, Erickson MRS, and Abmayr SM. Identification of a Drosophila homologue to Crk by interaction with MBC. Gene. 1999;228:243-252. Abstract.

Keller, CA, Grill MA and Abmayr SM.  A role for nautilus in the differentiation of muscle precursors. Dev Biol. 1998;202:157-171. Abstract.

Abmayr SM, Keller CA. Drosophila myogenesis, and insights into the role of nautilus. Curr Topics Dev Biol. 1998;38:35-80. Abstract.

Erickson MRS, Galletta BJ, Abmayr SM. Drosophila mbc encodes a conserved protein that is essential for myoblast fusion, dorsal closure and cytoskeletal organization. J Cell Biol. 1997;138:589-603. Abstract.

Lin M-H, Bour BA, Abmayr SM, Storti RV. Ectopic expression of MEF2 in the epidermis induces epidermal expression of muscle genes and abnormal muscle development in Drosophila. Dev Biol. 1997;182:240-255. Abstract.

Keller CA, Erickson MS, Abmayr SM.  Misexpression of nautilus induces myogenesis in cardioblasts and alters the pattern of somatic muscle fibers. Dev Biol. 1997;181:197-212. Abstract.

Rushton E, Drysdale R, Abmayr SM, Michelson AM, Bate M.  Mutations in a novel gene, myoblast city, provide evidence in support of the founder cell hypothesis for Drosophila muscle development. Development. 1995;121:1979-1988. Abstract.

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;9:730-741. Abstract.

Abmayr SM, Erickson MS, Bour BA. Embryonic development of the larval body wall musculature of Drosophila. Trends Genet. 1995;11:153-159. Abstract.

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 USA. 1994;91:7520-7524. Abstract.

Abmayr SM, Workman JL. Preparation of nuclear extracts from cultured cells. In: Ausubel FM, Brent R, Kingston RE, Moore DD, Siedman JG, Smith JA, Struhl K, eds. Short Protocols in Molecular Biology. New York, NY: Greene Publishing Associates/Wiley Interscience; 1992:12.3-12.5.

Abmayr SM, Michelson AM, Corbin V, Young MW, Maniatis T.  nautilus, a Drosophila member of the myogenic regulatory gene family. In: Blau H, Kelly A, eds. Gene Expression and Neuromuscular Development. New York, NY: Raven Press;1992. Keystone Symposium Proceedings Series. 1-16.

Corbin V, Michelson AM, Abmayr SM, Neel V, Alcamo E , Maniatis T, Young MW.  A role for the Drosophila neurogenic genes in mesoderm differentiation. Cell. 1991;67:311-323. Abstract.

Michelson AM, Abmayr SM, Bate CM, Martinez Arias M, Maniatis T. Expression of a MyoD family member prefigures muscle pattern in Drosophila embryos. Genes Dev. 1991;4:2086-2097. Abstract.

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