Abstracts - Society for Developmental Biology

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experimental analysis. The jerboas, in contrast, are a group of bipedal desert-adapted rodents that provide an extraordinary
opportunity to address the developmental and genetic basis of limb evolution. Not only do their hindlimbs display the
bilateral loss of digits 1 and 5, they are closely related to mice with whom they can be developmentally compared.
Moreover they are small mammals that are plentiful in the wild and amenable to rearing in a laboratory setting. We find
that the shape of the early hindlimb bud of the three-toed jerboa differs from that of the forelimb and from the mouse
hindlimb bud. This narrowing of the footplate correlates with an increased expression of bmp4, an important regulator of
cell death and proliferation. At early condensation stages, the proximal aspects of five digital rays are initially specified,
but the first and fifth are truncated resulting in only three fully formed digits. Additionally, an increase in programmed cell
death in the non-digit tissue surrounding the small truncated condensations suggests excessive sculpting contributes to digit
loss. We are extending these studies to identify the genetic changes underlying evolutionary digit loss in the jerboa and are
investigating possible mechanistic convergence in the symmetric loss of lateral digits in horses.
Program/Abstract # 222
Functional characterization of Dlx intergenic enhancers in the developing mouse
Esau, Crystal, University of Ottawa, Ottawa, Canada; Poitras, Luc; Yu, Man; Lesage-Pelletier, Cindy; Fazel Darbandi,
Siavash; Ekker, Marc (University of Ottawa, Ottawa, Canada)
The Distal-less homeobox (Dlx) genes encode homeodomain transcription factors found in all animals of the phylum
Chordata. These genes are involved in early vertebrate development of limbs, sensory organs, branchial arches and the
forebrain (telencephalon and diencephalon). The mouse and human genomes each have six Dlx genes organized into
convergently transcribed bigene clusters (Dlx1/2, Dlx3/4 and Dlx5/6). In the forebrain, Dlx1/2and Dlx5/6 genes play
essential roles in GABAergic neuron proliferation, migration and survival. Each bigene cluster includes a short intergenic
region (~3.5-16kb) harboring cis-regulatory elements (CREs) that control expression of the Dlx genes. The Dlx1/2
intergenic region harbors the I12b/I12a CREs, while Dlx5/6 includes I56i/I56ii. In determining the regulatory roles of the
CREs on Dlx activity and forebrain development, we have characterized the phenotypic changes that occur in mice with a
targeted deletion of I12b or ofI56ii. The effect of a single nucleotide polymorphism (SNP) in the I56i enhancer which is
present in patients with autism spectrum disorder was also assessed. Mutant mice with a targeted deletion of I12b, I56ii or
I56i SNP are viable, fertile and do not show obvious developmental or behavioral defects. The deletion of each Dlx
enhancer studied thus far decreases Dlx expression. An increase in Dlx1 transcript levels may compensate for the
reductions in Dlx5and Dlx6 expression. We are determining the functional importance of the I56i enhancer through
characterization of the phenotypic changes in I56i null mice. This research will contribute to a better understanding of the
role intergenic enhancers play in Dlx forebrain function.
Program/Abstract # 223
Ectodysplasin regulates activator-inhibitor balance in murine tooth development through modulation of Fgf20
signaling
Haara, Otso, Institute of Biotechnology, University of Helsinki, Finland, Helsinki, Finland; Harjunmaa, Enni; Lindfors,
Päivi (Helsinki, Finland); Huh, Sung-Ho (St Louis, United States); Fliniaux, Ingrid; Åberg, Thomas; Jernvall, Jukka
(Helsinki, Finland); Ornitz, David M. (St Louis, United States); Mikkola, Marja L.; Thesleff, Irma (Helsinki, Finland)
Uncovering the origin and nature of phenotypic variation within species is the first step in understanding variation between
species. Mouse models with altered activities of critical signal pathways have highlighted many important genes and signal
networks regulating the morphogenesis of complex structures, such as teeth. The detailed analyses of these models have
indicated that the balanced actions of a few pathways regulating cell behavior modulate the shape and number of teeth.
Currently, however, most mouse models studied have had gross alteration of morphology, while analyses of more subtle
modification of morphology are required to link developmental studies to evolutionary change. Here we have analyzed a
signaling network involving Ectodysplasin (Eda) and Fibroblast growth factor 20 (Fgf20) that affects tooth morphogenesis
subtly. We found that Fgf20 is a major downstream effector of Eda, and affects Eda-regulated characteristics of tooth
morphogenesis including number, size and shape of teeth. Fgf20 function ispartly compensated for by other Fgfs, in
particular Fgf9 and Fgf4, and is part of an Fgf signaling loop between epithelium and mesenchyme. We showed that
removal of Fgf20 in an Eda gain-of-function mouse model results in an Eda loss-of-function phenotype in terms of reduced
tooth complexity and third molar appearance. However, the extra anterior molar, a structure lost during rodent evolution
50My ago, was stabilized in these mice.
Program/Abstract # 224
Prenatal administration of dexamethasone during early pregnancy negatively affects placental development and
function in mice