Congress Abstracts - Society for Developmental Biology

Embryonic development can often adjust its morphogenetic processes to counteract external perturbation. The existence of selfmonitoring
responses during pattern formation is of considerable importance to the biomedicine of birth defects, but has not been
quantitatively addressed. To understand the computational capabilities of biological tissues in a molecularly-tractable model system,
we induced craniofacial defects in Xenopus embryos, then tracked tadpoles with craniofacial deformities and used geometric
morphometric techniques to characterize changes in the shape and position of the craniofacial structures. Canonical variate analysis
revealed that the shapes and relative positions of perturbed jaws and branchial arches were corrected during the first few months of
tadpole development. Analysis of the relative movements of the anterior-most structures indicates that misplaced structures move
along the anterior-posterior and left-right axes in ways that are significantly different from their normal movements. Our data suggest
a model in which craniofacial structures utilize a measuring mechanism to assess and adjust their location relative to other local
organs. Understanding the correction mechanisms at work in this system could lead to the better understanding of the adaptive
decision-making capabilities of living tissues and suggest new approaches to correct birth defects in humans.
Program/Abstract # 209
Morphogenetic Mechanisms Regulated by Non-Canonical Signaling in the Face
Geetha-Loganathan, Poongodi Geetha-Log (Life Sciences Institute, Canada); Nimmagadda, Suresh; Fu, Katherine; Richman, Joy
(University of British Columbia, Canada)
WNTs that activate JNK-planar cell polarity pathways regulate convergent extension. The role of PCP pathways in later
organogenesis is not as well studied, but recent work has shown that Wnt5a mediated PCP signaling is central to limb morphogenesis.
In the period after neural crest cell migration has ceased, the prominences surrounding the primitive mouth elongate in the
craniocaudal axis while becoming narrower in the perpendicular or medio-lateral axis. Initially we asked whether the necessary
context to respond to putative non-canonical WNTs was present in the face. Indeed WNT11, a putative non-canonical WNT expressed
in the avian face strongly activated a reporter for JNK activity. Furthermore, reporter activity depend on the DEP domain of
Dishevelled, suggesting that PCP signaling was involved. In contrast, there was no activation of the canonical WNT reporter,
SuperTopflash. We next targeted RCAS::WNT11 retrovirus to the maxillary prominence (mp) in vivo. The majority of embryos
developed notches in the upper beak and also caused an earlier shortening and widening of the mp connsistent with a defect in CE.
These morphology changes were correlated with decreased expression of several human clefting genes. The data suggested that cell
organization was disrupted by global expression of WNT11. Tracking labelled maxillary cells in the presence of Wnt11 or Wnt3a
expressing cells implanted shows that the host cells were attracted to the source of Wnt11 and became greatly elongated whereas cells
exposed to Wnt3a remained rounded and did not migrate. Taken together, the data suggest that the normal role of WNT11 is to control
morphogenetic cell movements and to promote fusion of the lip via PCP signaling.
Program/Abstract # 210
Fat-Dachsous signaling coordinates polarity and differentiation of the craniofacial skeleton in zebrafish
Le Pabic, Pierre; Ng, Carrie; Schilling, Thomas (University of California-Irvine, USA)
Little is known about the mechanisms of cell-cell communication necessary to assemble skeletal elements of appropriate size and
shape. Skeletal progenitors may behave as coherent units by communicating via the planar cell polarity (PCP) pathway. In
Drosophila, two sets of factors control PCP independently: the Fat and the Frizzled (Fz) signaling systems. While a requirement for
components of the Fz system was recently demonstrated in regulating the oriented divisions and intercalations of chondrocytes in the
growth plates of long bones, a role for the Fat system in skeletal development has not been reported. We find that loss of Fat- or
Dachsous-orthologues in zebrafish results in craniofacial skeletal defects similar to those previously reported in Sox9a mutants,
including defects in prechondrocyte stacking and polarity – two PCP-regulated behaviors in other contexts such as gastrulation - as
well as a failure of chondrocytes to differentiate. Our chimaeric analysis demonstrates that Fat is both necessary and sufficient to
coordinate polarity and differentiation of cartilage in a non-cell autonomous manner. Lastly, we find that Fat regulates expression of
the cartilage differentiation gene Sox9a via the transcriptional co-repressor Atrophin2a. These results provide genetic evidence that
skeletal morphogenesis and differentiation are controlled through a conserved Fat signaling pathway, a process that has not previously
been associated with defects in skeletal tissue polarity.
Program/Abstract # 211
Two novel mouse models of craniofacial dysmorphology
Miller, Kerry Ann (Murdoch Childrens Research Institute, Australia); Tan, Tiong (Victorian Clinical Genetics Services, Australia);
Welfare, Megan; Farlie, Peter (Murdoch Childrens Research Institute, Australia)
Approximately one third of all congenital abnormalities involve the craniofacial structures, where they are frequently associated with
other clinical characteristics such as defects in the limbs and/or other organ systems. Thus delineating the molecular control of normal
development in any individual structure will impact on our understanding of craniofacial dysmorphologies. Our current knowledge of
the developmental processes governing anomalous development of the craniofacial complex is poor due to the deficits in our
understanding of normal development of these structures. We have identified two novel ENU mouse models of two distinct human
craniofacial dysmorphologies. Mutant snoopy embryos display a unilateral facial hypoplasia phenotype that involves the mandible,
mid-face and ears. These characteristics are very similar in appearance to the human condition Goldenhar syndrome. The
developmental origins of Goldenhar syndrome are not well documented and no genetic lesion has yet been associated with this
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