Yevgenya Grinblat

Position title: Professor, Biology Ph.D. (1993) Harvard University

Phone: (608) 265-3219

Address:
Research Interests: genetic control of cranial morphogenesis

Our research uses zebrafish as a model to interrogate 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. Mutations in human ZIC2 are linked to a congenital brain malformation, holoprosencephaly, and our studies to date have uncovered novel roles for zebrafish Zic2 in key cell lineages that comprise the head: the neural tube, the eye (including neural retina and ocular vasculature) and neural crest-derived craniofacial cartilages. Our findings indicate that Zic2 functions cell-autonomously in these lineages, consistent with data from other model systems where Zic2 is emerging as an important control of pluripotency and cell fate specification. How Zic2 functions in these processes is still poorly understood and we are using our unique collection of zebrafish tools and cutting-edge methods, e.g. CUT&RUN and in vivo proximity labeling, to address this gap in our knowledge.

The retina and rostral brain arise from the same embryonic primordium. The frequent association between holoprosencephaly (a cerebral malformation) and coloboma (a large gap in the retina) reflects this shared origin and suggests key genetic controls of retinal and brain development are also shared. Confocal image on the left shows the head of a zebrafish embryo, with brain nuclei in blue and portions of the eyes in purple (from Sedykh et al., 2017). Image on the right shows the eye of a zebrafish embryo that lacks functional Zic2 and has developed with retinal coloboma (imaging by I. Sedykh).

Selected Publications

Santistevan, N. J., et al. (2022) A forward genetic screen identifies a novel role for cacna2d3 in vertebrate habituation learning and startle threshold. PLoS ONE 17(7): e0270903. PMID: 35834485
Yoon, B., et al. (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
Pini, J., et al.(2020). ALX1-related Frontonasal Dysplasia Results From Defective Neural Crest Cell Development and Migration. EMBO Molecular Medicine, 12:e12013. PMID: 32914578
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
Sedykh, I., et al. (2018) Zebrafish Rfx4 controls dorsal and ventral midline formation in the neural tube. Dev Dyn, 247(4), 650-659. PMCID: PMC5854527.
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
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.

Complete list can be found here