Abstract
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.
Highlights
The Drosophila tumor suppressor, lethal giant larvae (Lgl), is an evolutionarily conserved and widely expressed cytoskeleton protein
We found that Lethal giant larvae 1 (Lgl1) protein was detected throughout the dorsal region of the LGE (dLGE) and olfactory bulb (OB) and highly expressed in the MCL, GCL and GL in wild-type mice (WT)
Lgl1 mutants have a smaller dLGE at E14.5, and develop a dLGE-like construction
Summary
The Drosophila tumor suppressor, lethal giant larvae (Lgl), is an evolutionarily conserved and widely expressed cytoskeleton protein. Lgl is essential for the establishment and maintenance of polarized epithelia, as well as cell polarity, which is associated with the asymmetric cell division of neuroblasts during fly development [1]. Loss of Lgl results in invasive cell behavior in the Drosophila follicular epithelium during border cell migration. There are two genes with strong homology to Drosophila Lgl (dLgl): Lgl, which is highly expressed in the developing brain and spinal cord in mice and Lgl, which is highly expressed. Lgl Is Required for Olfactory Bulb in Mice
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