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Research Interests
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 two brain subdivisions, the forebrain (including
the future cerebral cortex and thalamus) and midbrain (future optic
tectum), and on the roles of the zic gene family of zinc
finger transcription factors in their development. In humans, zic
genes are critical for normal brain development since mutations
in zics cause major birth defects, holoprosencephaly and
neural tube closure defects. In spite of their obvious importance,
the mechanism of their 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 brain abnormalities
in humans.
Teaching
Courses:
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've recently
earned graduate degrees:
Tina Samuels, CMB Training Program. Non-thesis Masters
Degree, January 2005.
Other Lab members
Matt Gillhouse, Technician
Selected
Publications
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.
Book chapters
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
Halloran
lab
Pelegri lab
Peterson
lab
Huttenlocher
lab
Useful zebrafish links
Zebrafish
sequencing project
Zebrafish
Information Network
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