title: Horizontal Basal Cell-Specific Deletion of Pax6 Impedes Recovery of the Olfactory Neuroepithelium Following Severe Injury.
abstract: In the mammalian olfactory epithelium (OE), olfactory receptor neurons (ORNs) are continuously regenerated throughout the animal's lifetime. Horizontal basal cells (HBCs) in the OE express the epithelial marker keratin 5 (K5) and the stem cell marker Pax6 and are considered relatively quiescent tissue stem cells in the OE. Pax6 is a key regulator of several developmental processes in the central nervous system and in sensory organs. Although Pax6 is expressed in the OE, its precise role remains unknown, particularly with respect to stem cell-like HBCs. To investigate the function of Pax6 in the developmental and regenerative processes in the OE, we generated conditional Pax6-knockout mice carrying a loxP-floxed Pax6 gene. Homozygous Pax6-floxed mice were crossed with K5-Cre transgenic mice to generate HBC-specific Pax6-knockout (Pax6-cKO) mice. We confirmed that the deletion of Pax6 expression in HBCs was sufficiently achieved in zone 1 of the OE in Pax6-cKO mice 3 days after methimazole-induced severe damage. In this condition, regeneration of the OE was dramatically impaired; both OE thickness and the number of ORNs were significantly decreased in the regenerated OE of Pax6-cKO mice. These results suggest that Pax6 expression is essential for HBCs to differentiate into neuronal cells during the regeneration process following severe injury.
authors: 1 Department of Developmental Neuroscience, Centers for Neuroscience, Tohoku University Graduate School of Medicine , Sendai, Miyagi, Japan .|2 Department of Otorhinolaryngology-Head and Neck Surgery, Tohoku University Graduate School of Medicine , Sendai, Miyagi, Japan .
authors: Jun
authors: J
authors: Suzuki
authors: 3 Department of Neurobiology, Duke University Medical Center , Durham, North Carolina.
authors: Katsuyasu
authors: K
authors: Sakurai
authors: 4 Department of Cellular Neurobiology, Brain Research Institute, Niigata University , Niigata, Japan .
authors: Maya
authors: M
authors: Yamazaki
authors: 4 Department of Cellular Neurobiology, Brain Research Institute, Niigata University , Niigata, Japan .
authors: Manabu
authors: M
authors: Abe
authors: 1 Department of Developmental Neuroscience, Centers for Neuroscience, Tohoku University Graduate School of Medicine , Sendai, Miyagi, Japan .
authors: Hitoshi
authors: H
authors: Inada
authors: 4 Department of Cellular Neurobiology, Brain Research Institute, Niigata University , Niigata, Japan .
authors: Kenji
authors: K
authors: Sakimura
authors: 2 Department of Otorhinolaryngology-Head and Neck Surgery, Tohoku University Graduate School of Medicine , Sendai, Miyagi, Japan .
authors: Yukio
authors: Y
authors: Katori
authors: 1 Department of Developmental Neuroscience, Centers for Neuroscience, Tohoku University Graduate School of Medicine , Sendai, Miyagi, Japan .
authors: Noriko
authors: N
authors: Osumi
mesh_terms: D000818:Animals; D005136:Eye Proteins / Q000235:genetics* / Q000378:metabolism; D017353:Gene Deletion; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D055495:Neurogenesis; D018034:Olfactory Receptor Neurons / Q000166:cytology / Q000378:metabolism*; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics* / Q000378:metabolism; D012038:Regeneration; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D005136:Eye Proteins; D018398:Homeodomain Proteins; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; C000605732:Pax6 protein, mouse; D012097:Repressor Proteins