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The effects of endogenous and exogenous retinoids on facial patterning

University of British Columbia

Retinoids have been known to influence cell migration, interaction, and differentiation, but their role in skeletal development is still unclear. We investigated the role of retinoic acid receptor (RAR) signaling in facial patterning in chicken embryos. Beads soaked in RAR pan-antagonist, AGN 193109, and implanted into the right nasal pit of stage 15 to 20 embryos induced mild skeletal abnormalities. In addition, Msx-1, Msx-2, Shh, and Fgf-8, expression were not altered, implying that AGN 193109 was not potent enough to completely inhibit all endogenous retinoid signaling in vivo. We indirectly studied the in vivo effectiveness of AGN 193109 by implanting embryos with both RAR antagonist and exogenous retinoic acid (RA) soaked beads to determine if the RAR antagonist could antagonize the RA induced teratogenic effect. We demonstrated that a low concentration of exogenous RA could result in failure of outgrowth of the prenasal cartilage and premaxilla. Moreover, the RA induced defects could be rescued by the cotreatment of RAR antagonist, suggesting that AGN 193109 was effective in antagonizing retinoid signaling in vivo for 18 hours and could not be dislodged from RARs by exogenous RA. RA treated embryos did not show any changes in Fgf-8 and Shh expression, implying that Fgf-8 and Shh were independent of retinoid signaling. However, ectopic expression of Msx-2 was induced by RA treatment and was not downregulated by the cotreatment of the RAR antagonist. This data indicated for the first time that Msx-2 was regulated by retinoid signaling but was not important for the patterning of the chicken upper beak. Most importantly, we demonstrated that a temporary downregulation of Msx-1 in stage 24 RA treated embryos resulted in failure of outgrowth of the prenasal cartilage and premaxilla, but this downregulation was recovered by the cotreatment of RAR antagonist. Thus, our study revealed that maintenance of Msx-1 between stage 20 and stage 24 was essential for the outgrowth of the chicken upper beak.

Thesis/Dissertation

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2009-08-05

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http://hdl.handle.net/2429/11766

Dental Science

University of British Columbia

UBCV

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