Ectopic expression of luteinizing hormone-releasing hormone and peripherinin the respiratory epithelium of mice lacking transcription factor AP-2 alpha

The vertebrate transcription factor activator protein-2 (AP-2 alpha) is inv olved in craniofacial morphogenesis. In the nasal placode AP-2 alpha expres sion delineates presumptive respiratory epithelia from olfactory epithelia, with AP-2 alpha expression restricted to the anterior region of the respir atory epithelium (absent from the olfactory epithelium) at later stages. To address the role AP-2 alpha plays in differentiation of cell groups in the nasal placode, the spatiotemporal expression pattern of four markers norma lly associated with olfactory epithelial structures was analyzed in mice la cking AP-2 alpha. These markers were the intermediate filament protein peri pherin, the neuropeptide luteinizing hormone-releasing hormone (LHRH), the neural cell adhesion molecule (NCAM) and the olfactory transcription factor Olf-1. Development of cells expressing these markers was similar in both g enotypes until embryonic day 12.5 (E12.5), indicating that the main olfacto ry epithelium and olfactory pit formation was normal. At E13.5 in mutant mi ce, ectopic LHRH neurons and peripherin axons were detected in respiratory epithelial areas, areas devoid of Olf-1 and NCAM staining. Over the next fe w days, an increase in total nasal LHRH neurons occurred. The increase in n asal LHRH neurons could be accounted for by LHRH neurons arising and migrat ing out of respiratory epithelial regions on peripherin-positive fibers. Th ese results indicate that AP-2 alpha is not essential for the separation of the olfactory and respiratory epithelium from the nasal placode and is con sistent with AP-2 alpha preventing recapitulation of developmental programs within the respiratory epithelium that lead to expression of LHRH and peri pherin phenotypes. (C) 2000 Elsevier Science Ireland Ltd. All rights reserv ed.