Meeting Abstract

P1.1  Jan. 4  The role of Wnt signaling in craniofacial patterning BRUGMANN, S.A.*; GREGORIEFF, A.; LEUCHT, P.; CLEVERS, H.; HELMS, J.A.; Stanford University, Stanford, CA; Hubrecht Laboratory, The Netherlands; Stanford University,Stanford, CA; Hubrecht Laboratory, The Netherlands; Stanford University,Stanford, CA

Wnt signaling has been implicated in numerous aspects of craniofacial development, including the generation of neural crest cells and the patency of cranial sutures. Herein, we examined the role of Wnt signaling during development of the facial prominences. We observed that Wnt responsive cells define distinct boundaries within the frontonasal prominence (FNP). By E9.5 the central region of the FNP is devoid of Wnt responsive cells. This marked absence of Wnt responsiveness in the FNP is maintained to E15.5 and beyond, and delineates the midline infranasal depression (also known as the philtrum) from the more lateral regions of the midface. To confirm a role for Wnt signaling in medial/lateral patterning we used two separate methods to attenuate Wnt signaling. First, we inhibited Wnt signaling by knocking out two intracellular enhancers of Wnt signaling, Lef1 and TCF4 (i.e., Lef1-/-/TCF4-/-). Second, we used in utero gene transfer to inhibit Wnt signaling by infecting murine embryos with an adenovirus expressing the soluble Wnt inhibitor, Dickkopf 1 (Dkk1). Attenuating Wnt signaling using both experimental conditions resulted in the expansion of facial midline. Midline expansion, defined by an increased distance between lateral populations of Wnt responsive cells in TOPgal reporter mice, was often accompanied by a flattened infranasal depression and/or a dysmorphic nasal septum. We examined the in situ hybridization patterns for Wnt target genes and performed histological analyses in embryos with expanded midlines to characterize the molecular and cellular nature of this phenotype. Collectively these data begin to elucidate a role for Wnt signaling, independent of neural crest generation, in the development and patterning of the craniofacial complex.