Abstracts - Society for Developmental Biology

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degradation of Smad proteins. We show that overexpression of Smads lacking target residues for MAPK phosphorylation
completely rescues the dorsalized phenotype of Acsl4a depletion. Our results reveal a critical role for LC-PUFA
metabolism in BMP receptor-regulated Smad activity and, as a consequence, dorsoventral patterning. This is the first
report linking LC-PUFA metabolism and BMP signal regulation. BMP receptor-regulated Smads also play numerous key
roles in embryonic development and bone homeostasis and our findings may reveal ways that LC-PUFAs influence these
processes.
Program/Abstract # 324
Foxh1-Groucho transcriptional switching and spatiotemporal regulation of Nodal expression during early
embryonic development
Halstead, Angela M.; Wright, Chris, Vanderbilt University, Nashville, United States
Correct patterning during embryogenesis is greatly dependent upon proper regulation of the TGFβ-related gene Nodal,
which encodes a ligand essential for germ layer formation (mesendoderm induction) and establishment of left-right (L-R)
asymmetry in all vertebrates. The regulation of Nodal during these processes has been rigorously studied since its
discovery, but how Nodal and other members of a “Nodal gene cassette” (Nodal, inducer; Lefty, feedback antagonist; and
Pitx2, effector) are dynamically regulated at the transcriptional level remains unclear. It has recently been proposed that in
Xenopus laevis the forkhead box protein Foxh1 functions as a transcriptional switch, positively or negatively regulating
Nodal transcription via interactions with the signal transducer phospho-Smad2 (pSmad2), or the co-repressor Groucho 4
(Grg4), respectively. Much is known on how Foxh1/pSmad2 interactions affect Nodal transcription, but little is known
about the Foxh1/Grg4 interaction in repressing Nodal signaling, and whether or not this transcriptional switch mechanism
is conserved in higher vertebrates. We are deriving a mouse line in which this interaction is disrupted specifically by a
single amino acid alteration in the Grg4 binding domain of Foxh1. Defects resulting from the disruption will be examined
during gastrulation and L-R asymmetry specification to gain insight into how this interaction affects Nodal signaling and
the cell and tissue responses that are associated with differentiation or morphogenesis. I will also present ideas on how the
new mouse lines will allow investigation of occupancy and epigenetic effects at Nodal and other target gene loci.
Program/Abstract # 325
A sub-circuit of the sea urchin GRN integrates spatial information to pattern the embryonic skeleton
McIntyre, Daniel C.; McClay, David, Duke University, Durham, United States
The Gene Regulatory Network (GRN) driving the first 30 hours of development in the sea urchin effectively explains how
most tissues in the embryo are specified. Yet the current GRN is not sufficient to explain the complex morphology of the
developing embryo. In particular, pattering of the embryonic skeleton is not explained, even though the GRN describing
how the mesenchyme cells which produce it are specified is extremely well understood. It is known that signals including
VEGF and FGF, coming from a restricted set of ectodermal cells communicate this patterning information to the
mesenchyme cells. However, these signals are final messengers, the end result of a process which identifies the site of
skeleton formation from a thin band of ectodermal cells neighboring the endoderm- the border ectoderm (BE). To do this,
the cells in the BE must utilize a GRN capable of integrating several spatial inputs in order to locate and refine the
expression patterns of those signals. In this report we demonstrate the existence of a unique sub-circuit of the ectoderm
GRN which is activated by endodermal Wnt signaling. This sub-circuit then uses positional information provided by
TGFB signaling along the secondary embryonic axis to define the expression of a series of transcription factors that
together limit signaling molecule expression in the ectoderm. Ongoing research using mathematical modeling will show
how the negative regulatory logic used by this network is capable of creating the sharp and limited expression of Vegf
observed in the embryo. This research shows how a complex3-dimensional structure is patterned during embryogenesis
and may provide aparadigm for understanding other, more complex, developmental problems.
Program/Abstract # 326
Gata3 regulates branching morphogenesis and differentiation of the developing prostate.
Nguyen, Alana, McGill University, Montreal, Canada; Beland, Melanie (University of Quebec at Montreal, Montreal,
Canada); Bouchard, Maxime (McGill University, Montreal, Canada)
Organ development involves the precise spatial-temporal expression of regulatory transcriptional programs, which are
necessary for cell fate specification and tissue morphogenesis. Early in prostate development, we showed that deletion of
Gata3 in theurogenital sinus epithelium leads to budding defects associated with a reduction in basal-specific p63
transcription factor expression. To bypass the embryonic lethality of Gata3 deletion, we used Nkx3-1Cre to mediate
excision of the floxed Gata3 locus, showing that Gata3 is necessary for branching morphogenesis. The defect in branching
is coupled with an increase in cell division accompanied by atypical prostatic hyperplasia. We showed that these