Mary C. Mullins, Ph.D.

faculty photo
Professor of Cell and Developmental Biology
Department: Cell and Developmental Biology
Graduate Group Affiliations

Contact information
421 Curie Boulevard
Philadelphia, PA 19104-6058
Office: 215-898-2644
Fax: 215-898-9871
B.S. (Biochemistry, Summa Cum Laude)
University of Wisconsin, Madison, 1984.
Ph.D. (Biochemistry)
University of California at Berkeley, 1989.
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Description of Research Expertise

Research Interests
BMP signal transduction; molecular mechanisms of cell specification and maternal control in vertebrates.

Key words: maternal-effect, midblastula transition, Bone Morphogenetic Protein (BMP), signal transduction, Smad5, molecular-genetics, genomics, zebrafish, development, cell specification, embryonic axis

Description of Research

We are studying the molecular mechanisms by which a BMP (Bone Morphogenetic Protein) signal transduction pathway establishes different aspects of the vertebrate body plan. Various zebrafish mutants of BMP pathway components, as well as antisense knockdown approaches are used to dissect the molecular mechanisms by which this pathway establishes different cell types. We are studying the formation, function, and temporal regulation of a BMP activity gradient, which is implicated in specification of diverse cell types along the dorsal-ventral axis. We have shown that this gradient is essential in neural crest specification and is linked to dorsal-ventral patterning of neural tissue. Moreover, a subset of our defined components also function in post-embryonic heart development. Misregulation of BMP signaling leads to a debilitating disease in humans called FOP. We are currently trying to establish a model for FOP in the zebrafish.

Elaboration of the vertebrate body plan relies not only on zygotic processes, but also on maternally-controlled processes. That is, processes that depend on products derived from the mother that are deposited into the oocyte and are critical for proper development of the embryo. To this end we performed a large-scale maternal-effect mutant screen, not previously performed in a vertebrate, to identify mutants of key genes specifically required in the mother for oocyte development, egg activation, fertilization, the midblastula transition, and establishment of the axes of the vertebrate embryo. We identified numerous mutants in these processes and are studying the molecular and cellular basis for the defects, including positional cloning of the mutated genes.

Rotation Projects
1. Studies of maternal regulation of embryonic development, including the midblastula transition and animal-vegetal polarity.
2. Positional cloning of maternal control genes in the zebrafish.
3. Molecular activities of type I BMP receptors.
4. Studies on the action of BMPs as heterodimers versus homodimers.
5. The post-embryonic role of BMP signaling in heart development.

Lab personnel:
Bill Vought, research technician
Hong Zhang, research specialist
David Cobb, joint fish facility manager
Mona Finch-Stephen, joint fish technician
Yaniv Elkouby, postdoctoral researcher
Daniel Bricker, postdoctoral researcher
Yvette Langdon, postdoctoral researcher
James Dutko, postdoctoral researcher
Francesca Tuazon, graduate student
Joe Zinski, graduate student
Amy Kugath, research specialist
Matias Escobar, graduate student
Ricardo Fuentes, postdoctoral researcher
Ben Tajer, graduate student
Allison Jamieson-Lucy, graduate student

Selected Publications

Elkouby, Y., Jamieson-Lucy, A., and Mullins, MC: Oocyte Polarization is Linked to the Chromosomal Bouquet, a Conserved Polarized Nuclear Configuration in Meiosis. PLoS Biology 14(1), January 2016.

Yvette G. Langdon, Ricardo Fuentes, Hong Zhang, Elliott W. Abrams, Florence L. Marlow, and Mary C. Mullins. : A Maternal Cathepsin B that Regulates Dorsoventral Patterning and Morphogenesis Development 143(6): 1016-28, March 2016.

Ge X, Grotjahn D, Welch E, Lyman-Gingerich J, Holguin C, Dimitrova E, Abrams EW, Gupta T, Marlow FL, Yabe T, Adler A, Mullins MC, Pelegri F. : Hecate/Grip2a Acts to Reorganize the Cytoskeleton in the Symmetry-Breaking Event of Embryonic Axis Induction. PLoS Gene 10(10), October 2014.

Kapp, L.D., Abrams, E.W., Marlow, F.L., and Mullins, M.C.,: The Integrator Complex Subunit 6 (Ints6) Confines the Dorsal Organizer in Vertebrate Embryogenesis. PLos Genet 9(10), October 2013.

Hashiguchi, M, and Mullins, M.C., : Anteroposterior and dorsoventral patterning are coordinated by an identical patterning clock. Development 140(9): 1970-80, May 2013.

Elliott W. Abrams, Hong Zhang, Florence L. Marlow, Lee Kapp, Sumei Lu, and Mary C. Mullins: Dynamic assembly of Brambleberry mediates nuclear envelope fusion during early development. Cell 150(3): 521-32, August 2012.

Dutko, James A. Mullins, Mary C.: SnapShot: BMP signaling in development. Cell 145(4): 636, 636.e1-2, May 13 2011.

Gupta, Tripti. Marlow, Florence L. Ferriola, Deborah. Mackiewicz, Katarzyna. Dapprich, Johannes. Monos, Dimitri. Mullins, Mary C.: Microtubule actin crosslinking factor 1 regulates the Balbiani body and animal-vegetal polarity of the zebrafish oocyte. PLoS Genetics 6(8): e1001073, 2010.

Little, S. C. and Mullins, M.C.: Bone morphogenetic protein heterodimers assemble heteromeric type I receptor complexes to pattern the dorsoventral axis. Nature Cell Biology 11(5): 637-43, May 2009 (Cover photo).

Marlow, Florence L. Mullins, Mary C.: Bucky ball functions in Balbiani body assembly and animal-vegetal polarity in the oocyte and follicle cell layer in zebrafish. Developmental Biology 321(1): 40-50, Sep 1 2008.

Tucker, Jennifer A. Mintzer, Keith A. Mullins, Mary C.: The BMP signaling gradient patterns dorsoventral tissues in a temporally progressive manner along the anteroposterior axis. Developmental Cell 14(1): 108-19, Jan 2008.

Bontems F, Stein A, Marlow F, Lyautey J,, Gupta T., Mullins M.C. and Dosch R.: The bucky ball gene controls germ plasm localization in the zebrafish oocyte. Current Biology 19(5): 414-22, March 10 2009.

Holloway BA, Gomez de la Torre Canny S, Ye Y, Slusarski DC, Freisinger, CM, Dosch R, Chou MM, Wagner DS, and Mullins MC: A novel role for MAPKAPK2 in morphogenesis during zebrafish development. PloS Genetics 5(3): e1000413, March 2009.

Qi Shen, Shawn C. Little, Meiqi Xu, Julia Haupt, Cindy Ast, Takenobu Katagiri, Stefan Mundlos, Petra Seemann, Frederick S. Kaplan, Mary C. Mullins, and Eileen M. Shore: Fibrodysplasia ossificans progressiva ACVR1 R206H mutation activates BMP-independent chondrogenesis and regulates zebrafish dorso-ventral patterning. Journal of Clinical Investigation 119(11): 3462-72, 2009.

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Last updated: 12/04/2017
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