Faculty

Mary C. Mullins, Ph.D.

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

Contact information
1152 BRB II/III
421 Curie Boulevard
Philadelphia, PA 19104-6058
Office: 215-898-2644
Fax: 215-898-9871
Education:
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:
Amy Kugath, research specialist
Manami Kobayashi, postdoctoral researcher
Jose Pelliccia, postdoctoral researcher
Robyn Allen, postdoctoral researcher
Hannah Greenfeld, graduate student
Ben Tajer, graduate student
Allison Jamieson-Lucy, graduate student
William Jones, graduate student
Jira White, post-baccalaureate student

Selected Publications

Greenfeld H, Lin J, Mullins MC.: The BMP signaling gradient is interpreted through concentration thresholds in dorsal-ventral axial patterning. PLoS Biol 19: e3001059, Jan 2021.

Allen RS, Tajer B, Shore EM, Mullins MC.: Fibrodysplasia ossificans progressiva mutant ACVR1 signals by multiple modalities in the developing zebrafish. Elife 9: e53761, Sep 2020.

Tuazon FB, Wang X, Andrade JL, Umulis D, Mullins MC.: Proteolytic Restriction of Chordin Range Underlies BMP Gradient Formation. Cell Rep 32: 108039, Aug 2020.

Abrams EW, Fuentes R, Marlow FL, Kobayashi M, Zhang H, Lu S, Kapp L, Joseph SR, Kugath A, Gupta T, Lemon V, Runke G, Amodeo AA, Vastenhouw NL, Mullins MC.: Molecular genetics of maternally-controlled cell divisions. PLoS Genet 16: e1008652, Apr 2020.

Li L, Wang X, Mullins MC, Umulis DM.: Evaluation of BMP-mediated patterning in a 3D mathematical model of the zebrafish blastula embryo. J Math Biol 80: 505-520, Jan 2020.

Fuentes R, Tajer B, Kobayashi M, Pelliccia JL, Langdon Y, Abrams EW, Mullins MC.: The maternal coordinate system: Molecular-genetics of embryonic axis formation and patterning in the zebrafish. Curr Top Dev Biol 140: 341-389, 2020.

Speer KF, Sommer A, Tajer B, Mullins MC, Klein PS, Lemmon MA.: Non-acylated Wnts Can Promote Signaling. Cell Rep 26: 875-883, Jan 2019.

Jamieson-Lucy A, Mullins MC.: The vertebrate Balbiani body, germ plasm, and oocyte polarity. Curr Top Dev Biol 135: 1-34, 2019.

Jamieson-Lucy A, Mullins MC.: Isolation of Zebrafish Balbiani Bodies for Proteomic Analysis. Methods Mol Biol 1920: 295-302, 2019.

Wallace Chelsea K, Bright Lauren A, Marx James O, Andersen Robert P, Mullins Mary C, Carty Anthony J: Effectiveness of Rapid Cooling as a Method of Euthanasia for Young Zebrafish (). Journal of the American Association for Laboratory Animal Science : JAALAS 57(1): 58-63, Jan 2018.

Mucha Bettina E, Hashiguchi Megumi, Zinski Joseph, Shore Eileen M, Mullins Mary C: Variant BMP receptor mutations causing fibrodysplasia ossificans progressiva (FOP) in humans show BMP ligand-independent receptor activation in zebrafish. Bone 109: 225-231, Apr 2018.

Kim Seongcheol, Alsrhani Abdullah, Zafreen Lala, Khandekar Gauri, Marlow Florence L, Abrams Elliott W, Mullins Mary C, Jagadeeswaran Pudur: G protein-coupled receptor gpr34l mutation affects thrombocyte function in zebrafish. British journal of haematology 180(3): 412-419, 02 2018.

Fuentes Ricardo, Mullins Mary C, Fernández Juan: Formation and dynamics of cytoplasmic domains and their genetic regulation during the zebrafish oocyte-to-embryo transition. Mechanisms of development Aug 2018.

Fuentes R, Letelier J, Tajer B, Valdivia LE, Mullins MC.: Fishing forward and reverse: Advances in zebrafish phenomics. Mech Dev 154: 296-308, Dec 2018.

Zinski J, Tuazon F, Huang Y, Mullins M, Umulis D.: Imaging and Quantification of P-Smad1/5 in Zebrafish Blastula and Gastrula Embryos. Methods Mol Biol 1891: 135-154, 2019.

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Last updated: 01/22/2021
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