Rebecca Burdine
Systems and Circuits
Systems and Circuits

Associate Professor of Molecular Biology

Areas of Research: Left-right patterning in the vertebrate embryo
Research Lab
433A Moffett Laboratory

Research Focus

Left-Right Patterning in the Vertebrate Embryo

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.

Selected Publications

  • Burdine RD, Caspary T. (2013) Left-right asymmetry: lessons from Cancun. Development. 140: 4465-70. Pubmed
  • Tarkar A, Loges NT, Slagle CE,...Burdine RD,...Omran H. (2013) DYX1C1 is required for axonemal dynein assembly and ciliary motility. Nat Genet. 45: 995-1003. Pubmed
  • Park CY, Wong AK, Greene CS,...Burdine RD, Troyanskaya OG. (2012) Functional knowledge transfer for high-accuracy prediction of under-studied biological processes. PLoS Comput Biol. 9: e1002957. Pubmed
  • Lenhart KF, Holtzman NG, Williams JR, Burdine RD. (2013) Integration of nodal and BMP signals in the heart requires FoxH1 to create left-right differences in cell migration rates that direct cardiac asymmetry. PLoS Genet. 9: e1003109. Pubmed
  • Panizzi JR, Becker-Heck A, Castleman VH,...Burdine RD,...Drummond IA. (2012) CCDC103 mutations cause primary ciliary dyskinesia by disrupting assembly of ciliary dynein arms. Nat Genet. 44: 714-19. PubMed
  • Daily J, Nash K, Jinwal U,...Burdine RD,...Weeber EJ. (2011) Adeno-associated virus-mediated rescue of the cognitive defects in a mouse model for Angelman syndrome. PLoS One. 6: e27221 PubMed
  • Lenhart KB, Lin SY, Titus TA, Postlethwait JH, Burdine RD. (2011) Two additional midline barriers function with midline lefty1expresion to maintain asymmetric Nodal signaling during left-right axis specification in zebrafish. Development. 138: 4405-10. PubMed
  • McSheene JC, Burdine RD. (2011) Examining the establishment of cellular axes using intrinsic chirality. Proc Natl Acad Sci. 108: 12191-92.  PubMed
  • Slagle CE, Aoki T, Burdine RD. (2011) Nodal-dependent mesendoderm specification requires the combinatorial activities of FoxH1 and eomesodermin. PLoS Genet. 7: e1002072. PubMed
  • Fogelgren B, Lin SY, Zuo X,...Burdine RD, Lipschutz JH. (2011) The exocyst protein Sec10 interacts with polycystin-2 and knockdown causes PKD phenotypes. PLoS Genet. 7: e1001361 PubMed
  • Becker-Heck A, Zohn IE, Okabe N,...Burdine RD. (2011) The novel coiled-coil domain containing protein CCDC40 is essential for motile cilia function and left-right axis formation. Nat Genet. 43: 79-84. PubMed
  • Sullivan-Brown J, Bisher ME, Burdine RD. (2011) Embedding, serial sectioning and staining of zebrafish embryos using JB-4 resin. Nat Protoc. 6: 46-55. PubMed
  • Miri A, Daie K, Burdine RD, Aksay E, Tank DW. (2010) Regression-based identification of behavior-encoding neurons during large scale optical imaging of neural activity at cellular resolution. J Neurophysiol. 105: 964-80. PubMed
  • Xu B, Feng X, Burdine RD. (2010) Categorical data analysis in experimental biology. Dev Biol. 348: 3-11. PubMed
  • Jaffe KM, Thiberge SY, Bisher ME, Burdine RD. (2010) Imaging cilia in zebrafish. Methods Cell Biol. 97: 415-35. PubMed
  • Jaffe KM, Burdine RD. (2010) More than maintenance? A role for IFT genes in planar cell polarity. J Am Soc Nephrol. 21: 1240-41. PubMed
  • Serluca FC, Xu B, Okabe N,...Burdine RD. (2009) Mutations in zebrafish leucine-rich repeat-containing six-like affect cilia motility, result in pronephric cysts, but have variable effects on left-right patterning. Development. 136: 1621-31. PubMed
  • Okabe N, Xu B, Burdine RD. (2008) Fluid dynamics in Zebrafish Kupffer's vesicle. Dev Dyn. 237: 3602-3612. PubMed
  • Baker K, Holtzman NG, Burdine RD. (2008) Direct and indirect roles for nodal signaling in rwo axis conversions during asymmetric morphogenesis of the Zebrafish heart. Proc Natl Acad Sci. 105: 13924-29. PubMed
  • Weber S, Taylor JC, Winyard P,...Burdine RD. (2008) SIX2 and BMP4 mutations associate with anomalous kidney development. J Amer Soc Nephr. 19: 891-903. PubMed
  • Sullivan-Brown J, Schottenfeld J, Okabe N,...Burdine RD. (2008) Zebrafish mutations affecting cilia motility share similar cystic phenotypes and suggest a mechanism of cyst formation that differs from pkd2 morphants. Dev Biol. 314: 261-75. PubMed
  • Fan X, Hagos EG, Xu B, Sias C, Kawakami K, Burdine RD, Dougan ST. (2007) Nodal signals mediate interactions between the extra-embryonic and embryonic tissues in zebrafish. Dev Biol. 310: 363-78. PubMed
  • Schottenfeld J, Sullivan-Brown J, Burdine RD. (2007) Zebrafish curly up encodes a pkd2 ortholog that restricts left-side-specific expression southpaw. Development. 134, 1605-15. PubMed
  • Lin SY, Burdine RD. (2005) Brain asymmetry: switching from left to right. Curr Biol. 15: R343-45. PubMed
  • Dutta S, Dietrich JE, Aspock G, Burdine RD,...Varga ZM. (2005) pitx3 defines an equivalence domain for lens and anterior pituitary placode. Development. 132: 1579-90. PubMed
  • Hostetter CL, Sullivan-Brown JL, Burdine RD. (2003) Zebrafish pronephros: a model for understanding cystic kidney disease. Dev Dyn. 228: 514-22. PubMed
  • de la Cruz JM, Bamford RN, Burdine RD,...Muenke M. (2002) A loss-of-function mutation in the CFC domain of TDGF1 is associated with human forebrain defects. Hum Genet. 110: 422-28. PubMed
  • Concha ML, Burdine RD, Russell C, Schier AF, Wilson SW. (2000) A nodal signaling pathway regulates the laterality of neuroanatomical asymmetries in the zebrafish forebrain. Neuron. 28: 399-409. PubMed
  • Burdine RD, Schier AF. (2000) Conserved and divergent mechanisms in left-right axis formation. Genes Dev. 14: 763-76. PubMed
  • Bamford RN, Roessler E, Burdine RD,...Casey B. (2000) Loss-of-function mutations in the EGF-CFC gene CFC1 are associated with human left-right laterality defects. Nat Genet. 26: 365-69. PubMed
  • Yan YT, Gritsman K, Ding J, Burdine RD,...Shen MM. (1999) Conserved requirement for EGF-CFC genes in vertebrate left-right axis formation. Genes Dev. 13: 2527-37. PubMed

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