Lgl1 Is Required for Olfaction and Development of Olfactory Bulb in Mice.
Lethal giant larvae 1 (Lgl1) was initially identified as a tumor suppressor in Drosophila and functioned as a key regulator of epithelial polarity and asymmetric cell division. In this study, we generated Lgl1 conditional knockout mice mediated by Pax2-Cre, which is expressed in olfactory bulb (OB). Next, we examined the effects of Lgl1 loss in the OB. First, we determined the expression patterns of Lgl1 in the neurogenic regions of the embryonic dorsal region of the LGE (dLGE) and postnatal OB. Furthermore, the Lgl1 conditional mutants exhibited abnormal morphological characteristics of the OB. Our behavioral analysis exhibited greatly impaired olfaction in Lgl1 mutant mice. To elucidate the possible mechanisms of impaired olfaction in Lgl1 mutant mice, we investigated the development of the OB. Interestingly, reduced thickness of the MCL and decreased density of mitral cells (MCs) were observed in Lgl1 mutant mice. Additionally, we observed a dramatic loss in SP8+ interneurons (e.g. calretinin and GABAergic/non-dopaminergic interneurons) in the GL of the OB. Our results demonstrate that Lgl1 is required for the development of the OB and the deletion of Lgl1 results in impaired olfaction in mice.
Institute of Developmental Biology, School of Life Science, Shandong University, Jinan, 250100, Shandong, China.
Zhenzu
Z
Li
Institute of Developmental Biology, School of Life Science, Shandong University, Jinan, 250100, Shandong, China.
Tingting
T
Zhang
Jinan First People's Hospital, Jinan, 250011, Shandong, China.
Zhuchun
Z
Lin
The Second Hospital of Shandong University, Jinan, 250000, Shandong, China.
Congzhe
C
Hou
Institute of Developmental Biology, School of Life Science, Shandong University, Jinan, 250100, Shandong, China.
Jian
J
Zhang
Institute of Developmental Biology, School of Life Science, Shandong University, Jinan, 250100, Shandong, China.
Yuqin
Y
Men
SARITEX Center for Stem Cell, Engineering Translational Medicine, Shanghai East Hospital, Advanced Institute of Translational Medicine, Tongji University School of Medicine, Shanghai, 200123, China.|Center for Stem Cell&Nano-Medicine, Shanghai Advanced Research Institute, Chinese Academy of Sciences, Shanghai, 200123, China.|Shenzhen Key Laboratory for Molecular Biology of Neural Development, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518000, Guangdong, China.
Huashun
H
Li
Institute of Developmental Biology, School of Life Science, Shandong University, Jinan, 250100, Shandong, China.
Jiangang
http://orcid.org/0000-0001-9048-8211
J
Gao
D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal; D002452:Cell Count; D020868:Gene Silencing; D006023:Glycoproteins / Q000378:metabolism*; D007395:Interneurons / Q000166:cytology / Q000378:metabolism; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009154:Mutation / Q000235:genetics; D009830:Olfactory Bulb / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism*; D051762:PAX2 Transcription Factor / Q000378:metabolism; D012903:Smell / Q000502:physiology*
D006023:Glycoproteins; C524369:LGL1 protein, mouse; D051762:PAX2 Transcription Factor; C497319:Pax2 protein, mouse