Professor of Molecular Biology

Contact

rburdine@princeton.edu
609-258-7515
Moffett Laboratory, 159
Burdine Lab

Education

Ph.D., Yale University
B.S., Western Kentucky University

Curriculum Vitae

Research Area

Cell Biology, Development & Cancer

Research Focus

Left-right patterning in the vertebrate embryo



Research
Selected Publications
Biography
Honors & Awards
In my laboratory we are using the zebrafish to study how the left-right (LR) axis and pattern is established. Vertebrates appear bilaterally symmetric, but have internal asymmetries along the LR axis. This axis is revealed by the asymmetric placement of organs along the midline. For example, the human heart is located on the left of the body cavity, while the liver is located on the right. While genes implicated in LR patterning have been identified, we do not know how the LR axis is established, how the axis is aligned with the existing dorsal-ventral and anterior-posterior axes, or how LR information is received and interpreted by developing organs. Proper LR axis formation is critical for organogenesis as correct organ placement allows for proper connectivity with the developing vasculature. In humans, defects in LR patterning often manifest as congenital heart disease. Our current studies focus on a pathway known to be involved in left-right patterning, and on identifying new genes involved in this process.

The role of Nodal signaling in left-right patterning

In all vertebrates, components of the Nodal signaling pathway are expressed asymmetrically in the left lateral plate mesoderm, a tissue that will give rise to many asymmetric visceral organs. These components include the nodal ligand, the feedback inhibitor lefty, and the downstream transcription factor pitx2. In zebrafish we have an additional asymmetric expression domain for these genes in the developing brain. We are using zebrafish one-eyed pinhead (oep) mutants to explore the role of Nodal signaling in LR patterning of the viscera and brain. Oep is a member of the EGF-CFC family of proteins, which act as co-factors that are absolutely required for Nodal signaling. In oep mutants, asymmetric organs in the viscera and brain are still asymmetrically placed, but their positioning is randomized compared to wild-type controls. For example, the pancreas is correctly positioned on the right in approximately half of oep embryos, and on the left in the other half. This suggests Nodal is not required to generate asymmetries, but is required to properly direct their asymmetric position such that a consistent pattern is achieved. Future work in the lab will focus on when and where the Nodal signaling pathway is required for proper LR patterning and how this pathway provides directional information to developing organs.

Understanding how organs obtain asymmetric positions

How an organ obtains its final asymmetric position is not understood. Organs such as the heart and pancreas form in the midline, and obtain asymmetric positions later in development. To examine the cell movements that occur during this process, we are taking advantage of the transparency of zebrafish embryos. We are using GFP transgenics to observe cell behaviors during organ morphogenesis in the living embryo. To complement this descriptive approach, we are studying new zebrafish mutants to identify additional genes that affect LR organ patterning. In Class I mutants, organs that are normally asymmetric remain in midline positions. The identification of the genes affected in these mutants will further our understanding of how organs are asymmetrically positioned. Class II mutants have a complete reversal of asymmetric organs in half of the mutant embryos, and wild-type LR patterning in the other half. Class III mutants have randomized organ positioning similar to what is observed in oep mutants. Some of the Class III mutations have additional defects in the kidney. Cloning and characterizing the genes affected in these mutants will provide insights into how the embryos establishes and patterns the LR axis, and how these genes may be used in other contexts, such as kidney formation.




Maerker M, Getwan M, Dowdle ME, McSheene JC, Gonzalez V, Pelliccia JL, et al. Bicc1 and Dicer regulate left-right patterning through post-transcriptional control of the Nodal inhibitor Dand5. Nat Commun. 2021 ;12(1):5482. PubMed
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Willgoss T, Cassater D, Connor S, Krishnan ML, Miller MT, Dias-Barbosa C, et al. Measuring What Matters to Individuals with Angelman Syndrome and Their Families: Development of a Patient-Centered Disease Concept Model. Child Psychiatry Hum Dev. 2021 ;52(4):654-668. PubMed
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Bird LM, Ochoa-Lubinoff C, Tan W-H, Heimer G, Melmed RD, Rakhit A, et al. The STARS Phase 2 Study: A Randomized Controlled Trial of Gaboxadol in Angelman Syndrome. Neurology. 2021 ;96(7):e1024-e1035. PubMed
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Patterson VL, Burdine RD. Swimming toward solutions: Using fish and frogs as models for understanding RASopathies. Birth Defects Res. 2020 ;112(10):749-765. PubMed
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Grimes DT, Patterson VL, Luna-Arvizu G, Schottenfeld-Roames J, Irons ZH, Burdine RD. Left-right asymmetric heart jogging increases the robustness of dextral heart looping in zebrafish. Dev Biol. 2020 ;459(2):79-86. PubMed
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Patel AL, Yeung E, McGuire SE, Wu AY, Toettcher JE, Burdine RD, et al. Optimizing photoswitchable MEK. Proc Natl Acad Sci U S A. 2019 ;116(51):25756-25763. PubMed
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Preston CC, Storm EC, Burdine RD, Bradley TA, Uttecht AD, Faustino RS. Nucleoporin insufficiency disrupts a pluripotent regulatory circuit in a pro-arrhythmogenic stem cell line. Sci Rep. 2019 ;9(1):12691. PubMed
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Harris A, Siggers P, Corrochano S, Warr N, Sagar D, Grimes DT, et al. ZNRF3 functions in mammalian sex determination by inhibiting canonical WNT signaling. Proc Natl Acad Sci U S A. 2018 ;115(21):5474-5479. PubMed
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Goyal Y, Jindal GA, Pelliccia JL, Yamaya K, Yeung E, Futran AS, et al. Divergent effects of intrinsically active MEK variants on developmental Ras signaling. Nat Genet. 2017 ;49(3):465-469. PubMed
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Jindal GA, Goyal Y, Humphreys JM, Yeung E, Tian K, Patterson VL, et al. How activating mutations affect MEK1 regulation and function. J Biol Chem. 2017 ;292(46):18814-18820. PubMed
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Pelliccia JL, Jindal GA, Burdine RD. Gdf3 is required for robust Nodal signaling during germ layer formation and left-right patterning. Elife. 2017 ;6. PubMed
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Stainier DYR, Raz E, Lawson ND, Ekker SC, Burdine RD, Eisen JS, et al. Guidelines for morpholino use in zebrafish. PLoS Genet. 2017 ;13(10):e1007000. PubMed
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Grimes DT, Burdine RD. Left-Right Patterning: Breaking Symmetry to Asymmetric Morphogenesis. Trends Genet. 2017 ;33(9):616-628. PubMed
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Jindal GA, Goyal Y, Yamaya K, Futran AS, Kountouridis I, Balgobin CA, et al. In vivo severity ranking of Ras pathway mutations associated with developmental disorders. Proc Natl Acad Sci U S A. 2017 ;114(3):510-515. PubMed
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Grant MG, Patterson VL, Grimes DT, Burdine RD. Modeling Syndromic Congenital Heart Defects in Zebrafish. Curr Top Dev Biol. 2017 ;124:1-40. PubMed
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Jaffe KM, Grimes DT, Schottenfeld-Roames J, Werner ME, Ku T-SJ, Kim SK, et al. c21orf59/kurly Controls Both Cilia Motility and Polarization. Cell Rep. 2016 ;14(8):1841-9. PubMed
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Grimes DT, Boswell CW, Morante NFC, Henkelman RM, Burdine RD, Ciruna B. Zebrafish models of idiopathic scoliosis link cerebrospinal fluid flow defects to spine curvature. Science. 2016 ;352(6291):1341-4. PubMed
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Burdine RD, Grimes DT. Antagonistic interactions in the zebrafish midline prior to the emergence of asymmetric gene expression are important for left-right patterning. Philos Trans R Soc Lond B Biol Sci. 2016 ;371(1710). PubMed
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Jindal GA, Goyal Y, Burdine RD, Rauen KA, Shvartsman SY. RASopathies: unraveling mechanisms with animal models. Dis Model Mech. 2015 ;8(8):769-82. PubMed
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Hjeij R, Onoufriadis A, Watson CM, Slagle CE, Klena NT, Dougherty GW, et al. CCDC151 mutations cause primary ciliary dyskinesia by disruption of the outer dynein arm docking complex formation. Am J Hum Genet. 2014 ;95(3):257-74. PubMed
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Kim CK, Miri A, Leung LC, Berndt A, Mourrain P, Tank DW, et al. Prolonged, brain-wide expression of nuclear-localized GCaMP3 for functional circuit mapping. Front Neural Circuits. 2014 ;8:138. PubMed
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Rebecca Burdine joined the faculty at Princeton in 2003. Her lab focuses on understanding the mechanisms that control left-right patterning and asymmetric organ morphogenesis.? The lab also explores other developmental process involving cilia, including kidney structure and skeletal formation.?? She was named the 44th Mallinckrodt Scholar for the Edward Mallinckrodt Jr. Foundation, and received a Scientist Development Career Award from the American Heart Association in 2003.? She is on the Editorial board for Cell Reports, and regularly serves on grant review panels for the NIH and NSF.? At Princeton, she teaches the undergraduate course Mol348 Cell and Developmental Biology with Professor Devenport, and team teaches the graduate course Mol506 Cell and Developmental Biology.
Dr. Burdine graduated summa cum laude from Western Kentucky University, majoring in Recombinant Gene Technology with a minor in Chemistry.? She received her Ph.D. from Yale University for her thesis work with Dr. Michael Stern that included identifying and characterizing C. elegans egl-17, one of the first FGFs identified in invertebrates.? She determined that EGL-17 provided a directional cue for migrating sex myoblasts, providing insight into the role of FGF signaling in cell migration.? Dr. Burdine carried out her postdoctoral research in the laboratory of Alexander F. Schier (Harvard) when he was at the Skirball Institute of Biomolecular Medicine at New York University.? Using zebrafish as a model system, she focused on Nodal signaling and the mechanisms underlying vertebrate left-right patterning.? Her work helped to ascertain that Nodal signaling is not required to generate organ asymmetry, but instead acts to consistently bias the asymmetric placement of these same organs.? How Nodal biases organ asymmetry is a major focus of her current research.
Dr. Burdine is also parent to a child with Angelman Syndrome.?? Dr. Burdine currently serves as Chief Scientific Officer for the Pitt-Hopkins Research Foundation, and is a founding member and current Chief Scientific Officer for the Foundation for Angelman Syndrome Therapeutics.? She also served on the Scientific Advisory Board for the Angelman Syndrome Foundation.

2015

Innovation Fund Award, Princeton University