Ectopic expression of luteinizing hormone-releasing hormone and peripherin in the respiratory epithelium of mice lacking transcription factor AP-2alpha.
The vertebrate transcription factor activator protein-2 (AP-2alpha) is involved in craniofacial morphogenesis. In the nasal placode AP-2alpha expression delineates presumptive respiratory epithelia from olfactory epithelia, with AP-2alpha expression restricted to the anterior region of the respiratory epithelium (absent from the olfactory epithelium) at later stages. To address the role AP-2alpha plays in differentiation of cell groups in the nasal placode, the spatiotemporal expression pattern of four markers normally associated with olfactory epithelial structures was analyzed in mice lacking AP-2alpha. These markers were the intermediate filament protein peripherin, 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 genotypes until embryonic day 12.5 (E12.5), indicating that the main olfactory epithelium and olfactory pit formation was normal. At E13.5 in mutant mice, ectopic LHRH neurons and peripherin axons were detected in respiratory epithelial areas, areas devoid of Olf-1 and NCAM staining. Over the next few days, an increase in total nasal LHRH neurons occurred. The increase in nasal LHRH neurons could be accounted for by LHRH neurons arising and migrating out of respiratory epithelial regions on peripherin-positive fibers. These results indicate that AP-2alpha is not essential for the separation of the olfactory and respiratory epithelium from the nasal placode and is consistent with AP-2alpha preventing recapitulation of developmental programs within the respiratory epithelium that lead to expression of LHRH and peripherin phenotypes.
Kramer
P R
PR
Cellular and Developmental Neurobiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20895, USA.
Guerrero
G
G
Krishnamurthy
R
R
Mitchell
P J
PJ
Wray
S
S
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D004627:Embryonic Induction / Q000235:genetics; D004847:Epithelial Cells / Q000502:physiology; D005260:Female; D018507:Gene Expression Regulation, Developmental; D007987:Gonadotropin-Releasing Hormone / Q000235:genetics* / Q000378:metabolism; D007381:Intermediate Filament Proteins / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins; D051379:Mice; D008807:Mice, Inbred BALB C; D008817:Mice, Mutant Strains; D009296:Nasal Cavity / Q000196:embryology*; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D019006:Neural Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000502:physiology; D009831:Olfactory Mucosa / Q000196:embryology*; D009833:Olfactory Pathways / Q000196:embryology; D064531:Peripherins; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D050656:Transcription Factor AP-2; D014157:Transcription Factors / Q000235:genetics*
D004268:DNA-Binding Proteins; C489921:Ebf1 protein, mouse; D007381:Intermediate Filament Proteins; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D019006:Neural Cell Adhesion Molecules; D064531:Peripherins; C493668:Tfap2a protein, mouse; D015534:Trans-Activators; D050656:Transcription Factor AP-2; D014157:Transcription Factors; D007987:Gonadotropin-Releasing Hormone