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
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.
Tina Samuels, CMB Training Program. Non-thesis Masters Degree, January 2005.
Matt Gillhouse, Technician
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.