125 iBio Research Building
- Research Areas
- Developmental genetics
We are working to understand how the correct shape and size of the vertebrate brain is programmed in the genome, and how this program is realized during embryonic development. Our experimental approach is centered on identifying genes that control and coordinate morphogenesis (shaping) and growth of the brain and eye primordia very early in embryogenesis. These studies are carried out in a model organism, the zebrafish Danio rerio. Zebrafish embryos are more accessible than mammalian embryos at the relevant stages, and can be manipulated with a variety of powerful experimental techniques. We have uncovered essential roles for zebrafish Zic genes, a conserved family of transcription factors, in controlling morphogenesis and growth of the brain and retinal primordia. In humans, zic genes are also critical for normal brain morphogenesis since mutations in zics 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 genes to function leads to holoprosencephaly and other birth defects in humans.
Zoology 151 – Introductory Biology
Zoology 555 – Laboratory in Developmental Biology
Graduate students currently supervised:
Molly Wagner Nyholm, Ph.D. candidate, Zoology
Molly’s research is aimed at understanding how the midbrain, including the optic tectum, is formed in the zebrafish embryos. The functions and transcriptional regulation of zic genes during midbrain formation are addressed in the context of the whole embryo, using antisense knock-down techniques and transgenesis.
Nick Sanek, Ph.D. candidate, Genetics Training Program
Nick is investigating the role of zic2 during formation of the forebrain, the anterior-most derivative of the neural tube. He is combining the techniques of reverse genetics (antisense knock-down assays) and forward genetics (identification of chromosomal lesions in zic gene loci) to understand the mechanism of zic function.
Students supervised who have recently earned graduate degrees:
Tina Samuels, CMB Training Program. Non-thesis Masters Degree, January 2005.
Other lab members:
Matt Gillhouse, Technician
- 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.
- Gillhouse, M. W. Nyholm, H. Hikasa, S.Y. Sokol, Y. Grinblat (2004) Two Frodo/Dapper homologs are expressed in the developing brain and mesoderm of zebrafish. Dev. Dynamics 230, 403-409.
- E. Wiellette, Y. Grinblat, M. Austen, E. Hirsinger, A. Amsterdam, C. Walker, N. Hopkins, M. Westerfield, H.L. Sive (2004). A combined haploid and insertional mutation screen in the zebrafish. Genesis 40:231-240
- Grinblat, Y. and Sive, H. (2001) zic gene expression marks anteroposterior pattern in the presumptive neurectoderm of the zebrafish gastrula. Dev. Dyn. 222(4):688-693.
- Wiellette, E., Grinblat, Y., Austen, M., Hopkins, N., and Sive, H. (2001) An insertional screen for identification of genes required for neural induction and patterning in the zebrafish. FASEB J. 15(5):A1071.
- Grinblat, Y., Gamse, J., Patel, M., and Sive, H. (1998) Determination of the zebrafish forebrain: induction and patterning. Development 125:4403-4416.
- Sagerström, C.G., Grinblat, Y., and Sive, H. (1996) Anteroposterior patterning in the zebrafish, Danio rerio: an explant assay reveals inductive and suppressive cell interactions. Development 122:1873-1883.
Grinblat, Lane, Sagerström and 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.
Zebrafish research community in Madison