Abstracts - Society for Developmental Biology

48
rapidly increased in size; thus fusion of each papilla was evident. The circumvallate papillae showed severe defects; for
example, invagination of the trenches started asymmetrically, forming longer and shorter trenches. The foliate papillae
elevated initially, and resulted in stunted trenches. We conclude that Six1 and Six4 function synergistically to form
gustatory papillae during development of the tongue.
Program/Abstract # 146
WNT signaling controls parasympathetic ganglion formation during submandibular gland development
Knosp, Wendy, NIDCR LCDB, Bethesda, United States; Knox, Sarah, Martin, Gail, University of California, San
Francisco, U.S.A); Hoffman, Matthew (Bethesda, United States)
Submandibular gland (SMG) organogenesis involves the coordinated development of the epithelium and neural crestderived
parasympathetic ganglia (PSG), which condense and associate with the primary epithelial duct. FGFR signaling is
required for both epithelial and PSG development as these structures are absent in Fgf10-/- embryos. Signals from the PSG
maintainthe keratin 5+ (Krt5+) progenitor cells in the epithelium but it is not known whether the epithelium plays an
inductive role in PSG development. We hypothesized that secreted factor(s) from the epithelial duct promote PSG
condensation and association with the epithelium. Wnt-reporter mice show that WNT signaling occurs in PSG neurons
early in development. We performed microarray analysis of early SMG end buds and ducts, identifying increased Wnt
gene expression in the duct. Exogenous WNT proteins promote PSG proliferation and WNT inhibitors disrupt the
epithelial-PSG association. To determine if FGFR signaling affects WNT signaling in the PSG we treated SMGs with
FGF7 and FGF10, which reduced WNT signaling, PSG condensation and association with the duct, and the number of
Krt5+ progenitor cells. We also used a genetic model to increase endogenous FGFR signaling, deleting the signaling
antagonists Sprouty1 and Sprouty2 (Spry1/2DKO), which results in a similar but more severe phenotype. In conclusion, we
have identified a novel role for WNT signaling in promoting PSG proliferation and association with the epithelial duct
during SMG development, which establishes neuronal-epithelial communication required for progenitor cell maintenance
and SMG development.
Program/Abstract # 148
Reprogramming of thymic epithelial cells in response to hyperactivation of Wnt/Beta-Catenin signaling during
embryonic development
Gordon, Julie; Manley, Nancy, University of Georgia, Athens, United States
Wnt/beta-catenin signaling is involved in many developmental processes, and in particular plays a critical role in cell fate
determination. Hyperactivation of the pathway has been shown to cause cellular transdifferentiation from one mature
epithelial cell type to another. In the current work we describe a mouse mutant in which the Wnt/beta-catenin signaling
pathway is ectopically activated in thymic epithelial cells (TECs) from E11.5 of embryonic development. This resulted in a
dramatic alteration in thymus structure: the thymus was devoid of lymphocytes, failed to become vascularized and was
encased in a dense mesenchymal capsule. Furthermore, the epithelial cells no longer formed the characteristic 3D network,
ceased proliferation and showed an altered epithelial marker profile, with a loss of ‘TEC’ markers and gain of ‘epidermis’
markers. Experiments are in progress to determine the ability of this transformed mutant thymus to integrate into normal
adult skin following transplantation. The Foxn1 transcription factor is required for epithelial cell differentiation and
proliferation in the thymus and skin, and it is intriguing to propose that tissue-specific roles and control mechanisms exist
for Foxn1 in the two organs. Interestingly, we observed a transient downregulation of Foxn1 in the mutant thymus. We
propose that suppression of Wnt signaling in TECs is required for Foxn1 to assume its thymus-specific role, and that
ectopic activation of the pathway causes a “switch” to its skin role. We are interested to define the molecular mechanisms
that underlie the altered epithelial cell fate observed in these mutants, and specifically those that control the tissue-specific
roles of Foxn1 in the thymus versus skin.
Program/Abstract # 149
YY1 control of Vegf expression in the visceral endoderm is essential for yolk sac angiogenesis
Rhee, Siyeon; Trask, Mary C.; Malatos, Joeseph; Kim, Chaekyu; Guerrero, Mara-Isel; Mager, Jesse; and Tremblay,
Kimberly D., UMass Amherst, Amherst, United States
Yin Yang-1 (YY1), a multifunctional protein essential for embryonic development, is aptly named based on its function as
both a repressor and as an activator of gene transcription. Even though YY1 has been shown to control cell proliferation
and chromatin remodeling in cells, its function in particular cell types during embryogenesis is largely unexplored. A
conditional knock-out (cKO) strategy using the FoxA3-Cre line was used to assess the role of YY1 in the embryonic
endoderm and visceral endoderm (VE). Although cKO embryos appear normal until E8.5, by E9.5 Yy1 cKO embryos are
delayed and display both a loss of VE cell-polarity as well as an apparent disruption of yolk-sac angiogenesis. The