Yevgenya Grinblat

Research Description:
Our research is broadly aimed at understanding gene networks that control cranial development in vertebrate embryos. We have tackled these complex networks from the vantage point of an important, but poorly understood node: a conserved zinc-finger transcription factor Zic2. We have uncovered novel roles for Zic2 in several lineages that comprise the head: the neural tube, the eye (including neural retina and ocular vasculature) and in neural crest-derived craniofacial cartilages. Zic genes encode highly conserved zinc-finger transcription factors, and mutations in human ZIC genes contribute to holoprosencephaly, a prevalent class of birth defects that affect the brain. This conservation assures us that analysis of Zic function in the experimentally accessible zebrafish embryo will advance our understanding of human ZIC function, and will ultimately help elucidate the manner in which failure of Zic function leads to holoprosencephaly, neural tube closure defects, and other congenital anomalies.

Representative Publications:

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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

Sanek, N.A. and Grinblat, Y. (2008). A novel role for zebrafish zic2a during forebrain development. Developmental Biology 317:325-335. PMCID: PMC2419112.

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.

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: PMC2409112.

TeSlaa, J.J., Nyholm, M. K., Keller, A., Grinblat, Y. (2013) Zebrafish Zic2a and Zic2b regulate neural crest and craniofacial development. Dev Biol. 380, 73-86. PMCID: PMC3886643.

Sedykh, I., TeSlaa, J.J., Tatarsky, R. L., Keller, A.N, Toops, K.A, Lakkaraju, A, Nyholm, M.K., Wolman, A., Grinblat, Y. (2016) Novel roles for the radial spokehead protein 9 in neural and neurosensory cilia. Sci. Rep. 6, 34437. PMCID PMC5143386.

Sedykh, I., Yoon, B., Roberson, L., Moskvin, O., Dewey, C. N., & Grinblat, Y. (2017). Zebrafish zic2 controls formation of periocular neural crest and choroid fissure morphogenesis. Dev Biol, 429(1), 92-104. PMCID: PMC5603172.

Sedykh, I., Keller, A.N, Yoon, B., Moskvin, O., Grinblat, Y. (2018) Zebrafish Rfx4 controls dorsal and ventral midline formation in the neural tube. Dev Dyn, 247(4), 650-659. PMCID: PMC5854527.

Grinblat, Y., & Lipinski, R. J. (2019). A forebrain undivided: Unleashing model organisms to solve the mysteries of holoprosencephaly. Dev Dyn, 248(8), 626-633. PMID: 30993762

Pini, J., Hu, Y.H., Kueper,J., Kawasaki, K., Yeung, P., Yoon, B., Carmichael, N., Toth Petroczy, A.K., Perroni, V., Maas, R. L., Grinblat, Y., and Liao, E.C. (2020). ALX1-related Frontonasal Dysplasia Results From Defective Neural Crest Cell Development and Migration. EMBO Molecular Medicine, 12:e12013. PMID: 32914578

Yoon, B., Yeung, P, Nicholas Santistevan, N.J., Lauren Bluhm, L., Kenta Kawasaki, K., Kueper, J, Dubielzig, R, Liao, E.C. , and Grinblat, Y. (2022). Zebrafish models of Alx-linked frontonasal dysplasia reveal a role for Alx1 and Alx3 in the anterior segment and vasculature of the developing eye. Biology Open PMID: 35142342

Santistevan, N. J., Nelson, J., Ortiz, E., Miller, A. H., Halabi, D.H., Sippl, Z., Granato, M., Grinblat, Y. A forward genetic screen identifies a novel role for cacna2d3 in vertebrate habituation learning and startle threshold (revised manuscript under review, PLOS ONE) https://biorxiv.org/cgi/content/short/2021.12.02.470952v1