Yevgenya Grinblat

 

 

Genetic mechanisms of patterning and morphogenesis in the vertebrate brain

E-mail: ygrinblat@wisc.edu

Research Strengths: Development: plasticity and repair

We are working to understand how the staggering complexity of the vertebrate brain is formed during embryogenesis by identifying genetic interactions that govern the early steps of brain development. Our studies focus on the roles of the Zic gene family of zinc finger transcription factors during vertebrate brain development. In humans, ZICs are critical for normal brain development and mutations in Zics cause major birth defects: holoprosencephaly and neural tube closure defects. In spite of their obvious importance, the mechanism of Zic function is poorly understood. We use a model organism, the zebrafish Danio rerio, for our studies because zebrafish embryos are more accessible to experimentation than mammalian embryos and offer us a variety of powerful experimental techniques. Using both in vitro (molecular cloning) and in vivo methods, such as micro-dissection, transgenesis and mutagenesis, we are working to understand (1) how zic genes function and (2) how their precise patterns of expression are controlled during early brain formation. Ultimately, this work will help us understand the normal functions of Zic genes, and the manner in which their failure to function contributes to human developmental abnormalities.

Selected Publications:

• Nyholm, M. K., S. Abdelilah-Seyfried, Y. and Grinblat. A novel genetic mechanism regulates dorsolateral hinge point formation during zebrafish cranial neurulation. Under revision for Journal of Cell Science.
• Sanek, N.A. and Y. Grinblat. Zebrafish zic2a patterns optic stalk/retinal precursors through modulation of the Hedgehog signaling pathway. Submitted to Development.
• Sanek, N.A. and Y. Grinblat. 2008. A novel role for zebrafish zic2a during forebrain development. Developmental Biology 317:325-335. [PDF]
• Nyholm, M., S-F. Wu., R.I. Dorsky, Y. Grinblat. 2007. The zebrafish zic2a-5 gene pair acts downstream of canonical Wnt signaling to control cell proliferation in the developing tectum. Development 134:735-746.
• Gillhouse, M., W. Nyholm, H. Hikasa, S.Y. Sokol, and Y. Grinblat. 2004. Two Frodo/Dapper homologs are expressed in the developing brain and mesoderm of zebrafish. Dev. Dynamics 230:403-409. [PDF]
• Wiellette, E., Y. Grinblat, M. Austen, E. Hirsinger, A. Amsterdam, C. Walker, N. Hopkins, M. Westerfield, and H.L. Sive. 2004. A combined haploid and insertional mutation screen in the zebrafish. Genesis 40:231-240. [PDF]
• Grinblat, Y., Lane, Sagerström and H.L. Sive. 1999. Analysis of Zebrafish development using explant culture assays. In The Zebrafish: Methods in Cell Biology, vol. 59 (ed. H. W. Dietrich, M. Westerfield and L. Zon). pp. 127-159. San Diego: Academic Press.