SCIENTIFIC REPORT 2004 - Sylvester Comprehensive Cancer Center

T U M O R C E L L B I O L O G Y P R O G R A M
DAZ family), and DeadSouth (in vasa family), are
localized to germ plasm and are related to germ
cell components in Drosophila and humans. All
three of these RNAs encode RNA-binding proteins.
The laboratory is interested in identifying
the downstream targets of these germ cell components
and their function in development. Most
recently they have shown that interfering with
Xdazl function eliminates or depletes primordial
germ cells (PGCs) because these fail to migrate
out of the endoderm. Another mRNA, VegT, encodes
a T-box transcription factor. Dr. King and
her colleagues have shown that maternal VegT is
required for germ layer (endoderm, mesoderm,
ectoderm) formation during gastrulation and specifically
for endoderm identity. Experimental approaches
used in these studies include the creation
of dominant negatives, antisense oligos, over-expression,
ectopic expression, frog transgenics,
transgenics, reverse transcription-polymerase
chain reaction (RT-PCR), immunocytochemistry,
and in situ hybridization. A new gene, Xcat4, appears
to control the cell cycle in early development, as
over-expression of part of this protein completely
blocks G1/S transition.
Dr. King and her colleagues also have found
that VegT and the germ plasm mRNAs localize by
at least two different mechanisms and at different
times during oogenesis. They have determined
the RNA signal required for proper localization
of Xcat-2 and VegT and are currently working on
isolating the proteins that bind these localization
signals. Their long-term goal is to characterize all
seven genes as to their role in development as well
as to characterize the transport systems involved
in their localization.
SELECTED PUBLICATIONS
2002
Kloc, M, Dougherty, MT, Bilinski, S, Chan, AP,
Brey, E, King, ML, Patrick, CW Jr., and Etkin,
LD. Three-dimensional ultrastructural analysis of
RNA distribution within germinal granules of
Xenopus. Developmental Biology 241:79-93,
2002.
Bubunenko, M, Kress, TL, Vempati, UD,
Mowry, KL, and King, ML. A consensus RNA
signal that directs germ layer determinants to the
vegetal cortex of Xenopus oocytes. Developmental
Biology 248:82-92, 2002.
2003
Zhou, Y, Zhang, J, and King, ML. Xenopus
ARH couples lipoprotein receptors with the AP-2
complex in oocytes and embryos and is required
for vitellogenesis. Journal of Biological Chemistry
278:44584-92, 2003.
Bruce, AE, Howley, C, Zhou, Y, Vickers, SL, Silver,
LM, King, ML, and Ho, RK. The maternally
expressed zebrafish T-box gene eomesodermin
regulates organizer formation. Development
130:5503-17, 2003.
HIGHLIGHTS/DISCOVERIES
• Demonstrated for the first time that a germ
plasm component is required for PGC specification
in a vertebrate. PGC migration out of
the endoderm is a critical step in PGC differentiation
and Xdazl is clearly involved. Dr. King
and her colleagues want to learn more about
this pathway and its requirements. They have
shown that in Xenopus, germ plasm RNAs are
under translational control and that most of
them encode RNA binding proteins.
• Observed that a single maternally expressed
gene, VegT, appears to control the patterning of
the Xenopus blastula. The laboratory’s studies on
maternal VegT, a T-box transcription factor,
have shown that it is essential for three important
steps in development. VegT is required for
endoderm specification, the production, activation,
or delivery of the mesoderm inducer, and
for maintaining the boundary between endoderm
and mesoderm. Their results strongly suggest
that the major mesoderm-inducing signal is
a post-transcriptional event in Xenopus.
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UM/Sylvester Comprehensive Cancer Center Scientific Report 2004