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Dev Biol 2012 May 01;3651:229-40. doi: 10.1016/j.ydbio.2012.02.033.
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Median facial clefts in Xenopus laevis: roles of retinoic acid signaling and homeobox genes.

The upper lip and primary palate form an essential separation between the brain, nasal structures and the oral cavity. Surprisingly little is known about the development of these structures, despite the fact that abnormalities can result in various forms of orofacial clefts. We have uncovered that retinoic acid is a critical regulator of upper lip and primary palate development in Xenopus laevis. Retinoic acid synthesis enzyme, RALDH2, and retinoic acid receptor gamma (RARγ) are expressed in complementary and partially overlapping regions of the orofacial prominences that fate mapping revealed contribute to the upper lip and primary palate. Decreased RALDH2 and RARγ result in a median cleft in the upper lip and primary palate. To further understand how retinoic acid regulates upper lip and palate morphogenesis we searched for genes downregulated in response to RARγ inhibition in orofacial tissue, and uncovered homeobox genes lhx8 and msx2. These genes are both expressed in overlapping domains with RARγ, and together their loss of function also results in a median cleft in the upper lip and primary palate. Inhibition of RARγ and decreased Lhx8/Msx2 function result in decreased cell proliferation and failure of dorsal anterior cartilages to form. These results suggest a model whereby retinoic acid signaling regulates Lhx8 and Msx2, which together direct the tissue growth and differentiation necessary for the upper lip and primary palate morphogenesis. This work has the potential to better understand the complex nature of the upper lip and primary palate development which will lead to important insights into the etiology of human orofacial clefts.

PubMed ID: 22405964
Article link: Dev Biol

Species referenced: Xenopus laevis
Genes referenced: actl6a aldh1a2 cad col2a1 h3-3a lhx8 msx2 rab40b rarg tfap2a
GO keywords: retinoic acid receptor signaling pathway [+]
Antibodies: Casp3 Ab1 Col2a1 Ab1 H3f3a Ab9
Morpholinos: aldh1a2 MO1 lhx8 MO1 msx2 MO1

Disease Ontology terms: orofacial cleft
Phenotypes: Xla Wt + BMS453 (fig.4.c, e) [+]

Article Images: [+] show captions