University of Wisconsin–Madison

Yevgenya Grinblat

Associate Professor, Zoology Ph.D. (1993) Harvard University

(608) 265-3219

Patterning and morphogenesis of the neural tube in zebrafish

Yevgenya Grinblat

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The central question of my research program is how the nervous system primordium acquires its correct shape and size during vertebrate development. Our studies focus on the Zic family of zinc-finger transcription factors and on their roles in the developing forebrain, neural retina and midbrain (future optic tectum). In humans, mutations in Zic genes are a significant cause of holoprosencephaly, a devastating birth defect that affects the cerebral cortex and other tissues. To understand how Zic genes participate in shaping the vertebrate brain and retina, we use a model organism, the zebrafish Danio rerio. Zebrafish embryos are accessible at all stages of development and are amenable to a variety of powerful experimental methods, including forward and reverse genetics, micromanipulation and high-resolution live imaging. Using these methods, we have demonstrated novel roles for Zic genes in regulating cell shape changes and cell cycle progression in the brain primordium, and in patterning and morphogenesis of the neural retina. Using Zic genes as an entry point, we are working to elucidate the gene networks and cellular interactions that drive these important morphogenetic processes.

grinblat - 1Figure(right): Retinal morphogenesis is disrupted after Zic2a expression is experimentally depleted or expanded, resulting in ventral retinal defects and coloboma. A: control embryo with normal retinal morphology 48 hours after fertilization; B: Zic2a-overexpressing sibling embryo with ventral retinal defects (J. TeSlaa, unpublished).

Selected Publications

  • Sedykh, I., et al. (2017). “Zebrafish zic2 controls formation of periocular neural crest and choroid fissure morphogenesis.” Dev Biol: in press
  • Sedykh, I., et al. (2016). “Novel roles for the radial spoke head protein 9 in neural and neurosensory cilia.” Sci Rep 6: 34437.
  • Teslaa, J. J., et al. (2013). “Zebrafish Zic2a and Zic2b regulate neural crest and craniofacial development.” Dev Biol 380(1): 73-86.
  • Sanek, N. A., et al. (2009). “Zebrafish zic2a patterns the forebrain through modulation of Hedgehog-activated gene expression.” Development 136(22): 3791-3800.
  • Nyholm, M. K., et al. (2009). “A novel genetic mechanism regulates dorsolateral hinge-point formation during zebrafish cranial neurulation.” J Cell Sci 122(Pt 12): 2137-2148.
  • Sanek, N. A. and Y. Grinblat (2008). “A novel role for zebrafish zic2a during forebrain development.” Dev Biol 317(1): 325-335.
  • Elsen, G. E., et al. (2008). “Zic1 and Zic4 regulate zebrafish roof plate specification and hindbrain ventricle morphogenesis.” Dev Biol 314(2): 376-392.
  • Nyholm, M. K., et al. (2007). “The zebrafish zic2a-zic5 gene pair acts downstream of canonical Wnt signaling to control cell proliferation in the developing tectum.” Development 134(4): 735-746.
  • Wiellette, E., et al. (2004). “Combined haploid and insertional mutation screen in the zebrafish.” Genesis 40(4): 231-240.
  • Gillhouse, M., et al. (2004). “Two Frodo/Dapper homologs are expressed in the developing brain and mesoderm of zebrafish.” Dev Dyn 230(3): 403-409.
  • Grinblat, Y. and H. Sive (2001). “zic Gene expression marks anteroposterior pattern in the presumptive neurectoderm of the zebrafish gastrula.” Dev Dyn 222(4): 688-693.
  • Grinblat, Y., et al. (1999). “Analysis of zebrafish development using explant culture assays.” Methods Cell Biol 59: 127-156.
  • Grinblat, Y., et al. (1998). “Determination of the zebrafish forebrain: induction and patterning.” Development 125(22): 4403-4416.
  • Sagerstrom, C. G., et al. (1996). “Anteroposterior patterning in the zebrafish, Danio rerio: an explant assay reveals inductive and suppressive cell interactions.” Development 122(6): 1873-1883.
  • Grinblat, Y., et al. (1994). “Functions of the cytoplasmic domain of the beta PS integrin subunit during Drosophila development.” Development 120(1): 91-102.
  • Zusman, S., et al. (1993). “Analyses of PS integrin functions during Drosophila development.” Development 118(3): 737-750.
  • Grinblat, Y., et al. (1989). “Isolation and characterization of the Drosophila translational elongation factor 2 gene.” Nucleic Acids Res 17(18): 7303-7314.

Complete list can be found here