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> Department of Cell Biology and Neuroscience
at Montana State University
Cell Biology and Neuroscience Faculty
Dr. Christa Merzdorf
Assistant Professor
Developmental Neurobiology
We study molecular mechanisms that underlie patterning of the vertebrate nervous
system during embryonic development. Read more
Lab website: Molecular BioSciences website
The foundation of nervous system development is laid during gastrula stages and
continues during neurula stages. During this process, part of the embryonic
ectoderm (the neurectoderm) is induced and subsequently patterned to form the
nervous system. Many regulatory genes are involved in this patterning process,
which ultimately allows region-specific differentiation of the neurectoderm into
the correct parts of the nervous system. Early players in neural patterning
include the genes of the zic family.
One major focus of our work is to understand the roles that the transcription
factor zic1 plays during early neural development, using Xenopus and chick embryos
as model systems. Developmental genes often play multiple parts throughout
development. Similarly, zic1 is involved not only in early patterning of the
neural plate, but also in other developmental processes that include induction
of the neural crest, formation of the midbrain/hindbrain boundary, in addition
to roles in cerebellum, eye, somite, and limb bud development. In order to
understand the activities of the zic1 gene at the molecular level, it is of great
interest to identify genes that are regulated by this transcription factor.
Thus, we have conducted a microarray screen in Xenopus, designed to identify genes
that are direct targets of zic1. One of these genes is the novel gene, Xfeb,
that may act as a protease and participates in patterning of the hindbrain.
Several other genes that we identified, participate in early neural crest formation.
Many additional genes from our screen await further study, including genes that
point to interesting, previously unknown, activities, in which zic genes may engage.
In other studies, we have shown that zic1 plays a role in the development of the
midbrain/hindbrain boundary (MHB). Formation of the boundary between the midbrain
(future optic tectum/processing of visual information) and the anterior hindbrain
(future cerebellum/coordinated movement, balance) is a critical step in CNS
development. The gene interactions that we study at the MHB include how the
transcription factor zic1 contributes to formation of the MHB and later to the
delay in neuronal differentiation that is characteristic for the MHB. In
addition to experiments in whole Xenopus embryos, we are using a tissue explant
system to recreate artificial MHBs in vitro that allow the study and manipulation
of gene expression in a more controlled environment.
We also focus on the early development of the neural crest and of somites.
Several genes that are important for early neural tube formation (including
zic genes, wnt genes, etc) are also important for neural crest formation and
somite development. Ultimately, we hope to understand the similarities and
differences in upstream and downstream regulatory mechanisms that allow these
genes to function in such diverse contexts. Our microarray screen is a valuable
resource for these studies.
Finally, developmental genes often occur as gene families. The zic gene family
comprises five members, which are highly homologous and are expressed in
overlapping, but also distinct areas during embryonic development. We are
studying these different family members to gain an understanding of their
shared and individual contributions to early neural development. These studies
may help us understand why our genome devotes five rather redundant genes to the
zic gene family.
Overall, the results from our studies will increase our understanding of the
molecular mechanisms that underlie early neural development. Our studies will
also answer questions about gene families and the multiple roles that developmental
genes can play in development.
Selected Publications
Li, S, Y. Shin, K. Cho, and C.S. Merzdorf (2006). The Xfeb gene is directly
upregulated by Zic1 in early neural development. Dev. Dyn. Jul 26; Epub ahead of print.
Sun Rhodes, L.S. and C.S. Merzdorf (2006). The zic1 gene is expressed in chick
somites but not in migratory neural crest. Gene Expr. Patterns 6:539-545.
Merzdorf, C.S. and H. Sive (2006). The zic1 gene is an activator of Wnt signaling.
Int. J. Dev. Biol 50:611-617.
Education
B.S. in Genetics, University of California/Davis
Ph.D. in Cell Biology, Harvard University
Postdoctoral studies in Developmental Biology; Whitehead Institute/Massachusetts
Insitute of Technology
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