Abstracts - Society for Developmental Biology

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abnormally dilated capillaries in the cKO yolk sac fail to be remodeled into large blood vessels, displaying a delay in
vessel maturation including a reduction in smooth muscle actin. Prior to the onset of these phenotypes at E9.5 we found a
significant increase in the percent of cleaved Caspase-3 positive cells in the yolk sac mesoderm of E9.0 cKO embryos
suggesting that loss of Yy1 in the VE promotes apoptosis and delays differentiation in the adjacent YY1-positive yolk-sac
mesoderm. Vascular endothelial growth factor (VEGF), a secreted growth factor known to be required for blood vessel
development and for protection from apoptosis, is downregulated in cKO embryos by E9.0. Because YY1 was recently
shown to directly bind to the Vegf promoter and activate Vegf expression, it seemed likely that the primary target of YY1
activity in the VE was Vegf. To test this hypothesis, cKO embryos were cultured from E8.5 through E9.5 with exogenous
VEGF and we found that VEGF rescued many of the defects noted in vivo. Taken together, these results suggest that the
role of YY1 in the VE is to promote angiogenesis and to moderate apoptosis in the adjacent mesoderm by activating Vegf
expression.
Program/Abstract # 150
Uncovering the function of TMED2 during trophoblast differentiation
Heba, Taghreed, Zakariyah, Abeer; Jerome-Majewska, Loydie A., McGill U, Montreal, Canada
Transmembrane emp24 domain trafficking protein 2, (TMED2) is a member of the p24 family of proteins involved in
vesicle transport between the ER and Golgi. During vesicular transport between the ER and Golgi p24 proteins function as
receptors for both cargos and coat proteins. Our group showed that Tmed2 is required for normal embryo and placental
development in mouse and that syncytiotrophoblast cells of the mouse labyrinth placenta failed to differentiate in
homozygous mutant embryos. In human placenta, we showed expression of TMED2 between 5.5 and 40 weeks of
gestation in all trophoblast cell types. We noted that early in gestation TMED2 was more highly expressed in
cytotrophoblast cells versus syncytiotrophoblast. Surprisingly, we found that TMED2 was more highly expressed in a
choriocarcinoma cell line, BeWo, which can be induced to differentiate and form syncytiotrophoblast when compared to
the JEG-3 cell line, which does not fuse to form syncytiotrophoblast. We hypothesized that TMED2 is required for fusion
of trophoblast cells during syncytiotrophoblast differentiation. To test this hypothesis we are examining the function of
TMED2 during trophoblast differentiation of BeWo and Jeg-3 cell lines. We will show our plans to ectopically express
TMED2 in Jeg-3 cells and to knockdown TMED2 expression in BeWo choriocarcinoma cells with shRNA. Our work
suggests that TMED2 is required for trafficking cargoes that are essential for placental development.
Program/Abstract # 151
Interference with glutamate signaling induces neural tube defects: Implications for antiepileptic drug action during
neural tube formation
Sequerra, Eduardo; Borodinsky, Laura, UC Davis, United States
Failure of neural tube closure leads to malformations known as neural tube defects (NTDs). Offspring of epileptic women
exhibit higher incidence of NTDs due to the use of antiepileptic drugs (AEDs) during pregnancy. The mechanisms through
which these drugs induce NTDs remain unclear. We hypothesize that neurotransmitter signaling is present at neural plate
stages and is important for neural tube formation. AEDs induce NTDs by impairing embryonic neurotransmitter signaling.
Immunostaining and calcium imaging experiments reveal that glutamate is expressed throughout the neural plate and its
cells are responsive to glutamate and NMDA. The AED valproic acid (VPA) inhibits these responses. We then
investigated whether NMDA receptor-mediated signaling influences neural tube formation by incubating early neural plate
stage embryos with the NMDA receptor antagonist, D-AP5 until neural tube closure was completed in control siblings. D-
AP5 increases the incidence of NTDs in a dose-dependent manner. In parallel, knocking down the NMDA receptor subunit
NR1 inhibits the responsiveness of neural plate cells to NMDA and induces open neural tube phenotype. Inhibiting NMDA
receptors increases the number of phospho-histoneH3-expressing neural plate cells, suggesting that glutamate signaling
regulates cell proliferation during neural tube formation. Interestingly, the induction of NTDs by VPA is accompanied by
increases in BrdU incorporation, in PCNA-labeled and total number of neural plate cells, indicating that VPA is interfering
with the normal cell cycle progression. These findings suggest that glutamate signaling regulates cell cycle exit during
neural tube formation and AEDs may interfere with this action.
Program/Abstract # 152
Developmental Retardation of Male Rat Brain, Testis Gonocytes According to Bisphenol A in vivo Exposure Time
Park, Cheol Ho; Park, Soo Jung; Kim, Sung Won; Kim, Ji Sun; Hwang, You Jin; Kim, Dae Young, Gachon University of
Medicine and Science, Incheon, Republic of Korea
Bisphenol A (BPA) is a endocrine disruptor chemicals (EDCs) and acts like estrogenic chemical. EDCs mainly occur
reproductive, nervous systemic disorders. Especially BPA, used in plastic like nursing bottle and resins which is utilized in