Associate Professor, Zoology
Ph.D. (1993) Harvard University
(608) 265-3219 Phone
(608) 265-3250 Lab
Patterning and morphogenesis of the neural tube in zebrafish
Visit the Grinblat Lab
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.
Figure(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B: Zic2a-overexpressing sibling embryo with ventral retinal defects (J. TeSlaa, unpublished).
- Goswami S, Tarapore RS, Teslaa JJ, Grinblat Y, Setaluri V, Spiegelman VS. (2010) MicroRNA-340- mediated degradation of microphthalmia-associated transcription factor mRNA is inhibited by the coding region determinant-binding protein. J Biol. Chem. 285: 20532-40. PMCID: PMC2898355
- Sanek, N.A., Taylor, A. A., Nyholm, M. K. and Grinblat, Y.. (2009) Zebrafish zic2a patterns the forebrain through modulation of Hedgehog-activated gene expression. Development 136:3791-3800 PMCID: PMC2766342
- Nyholm, M. K., Abdelilah-Seyfried, S., and Grinblat, Y.. (2009). A novel genetic mechanism regulates dorsolateral hinge point formation during zebrafish cranial neurulation. J Cell Science 122: 2137-2148 PMCID: PMC2723160
- Noubissi, F., Sanek, N.A., Kawakami, K., Minamoto, T., Moser, A., Grinblat, Y., Spiegelman, V.S. (2009) Wnt signaling stimulates transcriptional outcome of the Hedgehog pathway by stabilizing GLI1 mRNA. Cancer Res. 69, 8572-8578. PMCID: PMC2783483
- Sanek, N.A. and Grinblat, Y. (2008). A novel role for zebrafish zic2a during forebrain development. Developmental Biology 317:325-335 PMCID: PMC2409112
- Elsen, G.E., Choi, L., Millen, K., Grinblat, Y., Prince, V.E. (2008). Zic1 and Zic4 regulate zebrafish roof plate specification and hindbrain ventricle morphogenesis. Developmental Biology, 314:376-392 PMCID: PMC2268115
- Nyholm M., Wu, S-F., Dorsky R. I., Grinblat Y. (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
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