Abstracts - Society for Developmental Biology

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between fetal and maternal circulation. We have shown that Tmed2 is expressed in both allantois and chorion and is
required for normal labyrinth layer formation. We hypothesized that TMED2 is essential in the chorion or allantois for
normal interaction between the allantois and chorion- a critical step in placental labyrinth layer development. To test this
hypothesis, we have generated an ex-vivo allantois and chorion recombination model. In our model, we recapitulated the
early events of labyrinth layer development: chorioallantoic attachment, fusion of the mesothelium and allantois, and
chorionic trophoblast differentiation. We used in situ hybridization and immunohistochemistry to confirm the
chorioallantoic attachment event and to monitor development of labyrinth layer in the chimeric explants. We will then use
combinations of wildtype and Tmed2 null chorion and allantois in these ex-vivo cultures to follow branching
morphogenesis in the chorion. Our work will provide insight into the contribution o fplacental-specific vesicular transport
by TMED2 to labyrinth layer morphogenesis. Ultimately we will identify novel mechanisms that may be implicated in the
prediction and treatment of placental diseases such as EPL and IUGR.
Program/Abstract # 219
Cis-regulatory analysis of Ets1 expression in neural crest reveals important inputs from Sox and Hox factors
Barembaum, Meyer; Bronner, Marianne, California Inst of Technol, Pasadena, United States
Neural crest cells emigrate from the dorsal neural tube and migrate to diverse sites within the embryo to contribute to the
bones of the face, peripheral nervous system, melanocytes and other cell types. To identify regulatory connections that lead
to neural crest formation, we have investigated the cis-regulatory elements involved in the expression of neural crest
specifier gene Ets1. Ets1 is particularly interesting because it is uniquely expressed in cranial but not trunk neural crest
cells. Our previous results revealed Ets1 to be a direct input for expression of the neural crest specifier gene, Sox10, in the
cranial neural crest. We find that Ets1 is first expressed in the dorsal neural tube at 5 somites (stage 8) prior to Sox10, and
continues to be expressed in migrating neural crest of the head. To identify putative enhancer elements, we isolated a
genomic region, conserved between birds and mammals, which drives gene expression in a manner that recapitulates much
of the Ets1 expression in the neural crest. Mutation of SoxE putative transcription factor binding sites results in reduction
of enhancer activity in the neural crest, thus revealing a critical input for SoxE family members such as Sox9 and Sox10. A
putative Hox site also is required for neural crest expression. In contrast, a putative cMyc/E-box sequence appears to act as
a repressor binding site. Finally, a putative TFAP2a binding site mutation results in different responses at different times,
acting as a repressor binding site early but as an activator later in neural crest development. ChIP analysis and knockdown
of putative inputs are in progress to confirm dir
Program/Abstract # 220
Origin of the mammalian neural crest: from mouse, to rabbit, to human
Garcia-Castro, Martin I., Yale University, New Haven, United States
Neural crest (NC) cells are vertebrate-specific, arise early in development, migrate throughout the body, and contribute to
a wide variety of derivatives. Aberrant neural crest development results in a large number of human health conditions,
including cleft lip/palate, Hirschprung and Waardenburg syndromes, and melanoma and neuroblastoma. Therefore, neural
crest development is of great interest to basic biologists and translational researchers alike. Current knowledge of the
origin of neural crest cells is abundant in frog, fish, and chick embryos. Previously we identified the specification of NC
occurring prior to gastrulation and an essential role for the early marker Pax7 in chick embryos. Despite the wide use of the
mouse as a model organism, minimal progress has been gained towards understanding the early specification and induction
of the mammalian neural crest. Here we will report a multi-mammalian approach to advance our understanding of early NC
development with particular interest to contribute to human NC biology. We have investigated the role of the transcription
factor Pax7 in early murine NC development, and we attempted to identify early NC specification. To overcome
limitations of the mouse system, and embracing the benefits of multiple comparative samples of mammalian NC
development, we have incorporated the rabbit as an alternative mammalian model organism. Here we present for the first
time, the expression profile of markers of the NC gene regulatory network in the rabbit and the specification of NC in a
mammalian embryo. Finally we undertook complementary studies in humans through embryonic stem cell differentiation
and early embryo expression, to establish induction and ontogeny of human NC cells.
Program/Abstract # 221
Hindlimb evolution and the bilateral loss of digits in the bipedal jerboa
Cooper, Kimberly L.; Uygur, Aysu; Tabin, Clifford, Harvard Medical School, Boston, United States
Selective pressure to run or bound over great distances has repeatedly reduced the number of digits in diverse species. In
many cases, such as the large hooved animals including deer and horses, these extreme adaptive changes are found in
animals that are phylogenetically far removed from model organisms and in taxa that are themselves not amenable to