Congress Abstracts - Society for Developmental Biology

differentiation from common progenitor cells adjacent to the STM into gall bladder progenitor cells by maintaining Sox17 expression
and suppressing Pdx1 expression. Furthermore, the STM suppresses ectopic activation of the liver program in the posterior region of
the ventral foregut following hepatic induction. In particular, STM-derived FGF10, which starts to be expressed in the STM at E9.0,
contributes to the suppression of hepatic gene expression in the presumptive gall bladder and ventral pancreas regions through an
Fgf10/Fgfr2b/Sox9 signaling pathway. Thus, the STM plays pivotal roles in gall bladder development by both inductive and
suppressive effects.
Program/Abstract # 400
EpCAM Is an Endoderm-Specific Wnt Derepressor that Licenses Hepatic Development
Huiqiang Lu, Jun Ma, Yun Yang, Wenchao Shi, and Lingfei Luo* (Southwest University, China) Mechanisms underlying cell-typespecific
response to morphogens or signaling molecules during embryonic development are poorly understood. To learn how response
to the liver-inductive Wnt2bb signal is achieved, we identify an endoderm-enriched, single transmembrane protein, epithelial-celladhesion-molecule
(EpCAM), as an endoderm-specific Wnt derepressor in zebrafish. hi2151/epcam mutants exhibit defective liver
development similar to prt/wnt2bb mutants. EpCAM directly binds to Kremen1 and disrupts the Kremen1-Dickkopf2 (Dkk2)
interaction, which prevents Kremen1-Dkk2-mediated removal of Lipoprotein-receptor-related protein 6 (Lrp6) from the cell surface.
These data lead to a model in which EpCAM derepresses Lrp6 and cooperates with Wnt ligand to activate Wnt signaling through
stabilizing membrane Lrp6 and allowing Lrp6 clustering into active signalosomes. Thus, EpCAM cell autonomously licenses and
cooperatively activates Wnt2bb signaling in endodermal cells. Our results identify EpCAM as the key molecule and its functional
mechanism to confer endodermal cells the competence to respond to the liver-inductive Wnt2bb signal.
Program/Abstract # 401
Intestinal epithelial secretory cell differentiation is dependent on ascl 1a acting through Notch signaling.
Wallace, Kenneth; Roach, Gillian; Wallace, Rachel; Cameron, Amy; Ozel, Emrah; Hongay, Cintia; Baral, Reshica; Andreescu,
Silvana (Clarkson University, USA)
Intestinal epithelial cells initially choose between the enterocyte or secretory cell fate. After this initial decision, cells continue
differentiating into a variety of different subtypes. While the majority of cells within the intestinal epithelium are enterocytes,
secretory cells are interspersed in a characteristic pattern along the anterior to posterior axis. Previously, Notch signaling has been
demonstrated to participate in the decision between these two epithelial cell types. Here we identify ascl1a as the gene required to
initiate specification of the intestinal epithelial secretory fate with a loss of function mutation resulting in an epithelium consisting of
only enterocytes. Loss of ascl1a also coincides with loss of expression of the Notch ligand deltaD. To determine whether Notch
signaling is active in specifying epithelial cell fate throughout the entire period of ascl1a expression, we inhibited Notch signaling
using the gamma secretase inhibitor DAPT. Inhibition of Notch signaling during only two periods during the first half of
embryogenesis results in increases in ascl1a and deltaD expressing epithelial cells in addition to increased numbers of secretory cells
at 74 hpf. This indicates that Notch signaling is utilized for two discrete periods rather than continuously. While we observe early
increases in secretory cells, continuous Notch inhibition with DAPT to the end of embryogenesis does not significantly alter overall
numbers but instead changes the quantity of specific secretory cell subtypes. Lack of secretory cell increases at the end of
embryogenesis may result from a combination of differential roles/responses of Notch receptors to inhibition and incomplete reduction
of signaling.
Program/Abstract # 402
Molecular characterization and functional analysis associated with retinoic acid signaling pathway during gut regeneration in
the sea cucumber
Viera-Vera, Jorge; Stephanie, Ortíz-Troche; Díaz-Díaz, Lymarie; García-Arrarás, José E. (Universty of Puerto Rico, Puerto Rico)
The sea cucumber, Holothuria glaberrima, has proven to be an important non-classical research model for understanding the cellular
and molecular processes governing organ regeneration. This deuterostome regenerates most of its viscera after an induced
evisceration event, where the digestive tube is the first to do so through the formation of a blastema-like structure. To determine the
genetic network of intestinal regeneration, we focused on the characterization of genes related to the metabolism and function of
retinoic acid (RA), a known mediator of tissue regeneration in vertebrates. We also explored the effects of interfering with RA
signaling via citral and diethylaminobenzaldehyde (DEAB), two well-known inhibitors of retinaldehyde dehydrogenase (RALDH).
Analysis of various genetic libraries revealed the presence of genes associated to RA metabolism (short-chain dehydrogenase
reductase 7 and RALDH4) and to its function (retinoic acid receptor and retinoic acid X receptor). Additional sequence analyses
including: primary structure sequencing, phylogenetic analysis, protein domain prediction, and multiple sequence alignment further
confirmed their presence. Moreover, animals treated with RA synthesis inhibitors showed a smaller intestinal regenerate. These
animals also showed altered cellular dedifferentiation patterns and a 50% decrease in cell proliferation. These findings contribute
towards our understanding of RA function during adult regenerative organogenesis and provide a novel opportunity to determine the
cellular events linked to RA signaling in this re-emerging model system.
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