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Loss of the small GTPase Arl8b results in abnormal development of the roof plate in mouse embryos

Hashimoto, Keisuke, Yamaguchi, Yoshifumi, Kishi, Yusuke, Kikko, Yorifumi, Takasaki, Kanako, Maeda, Yurie, Matsumoto, Yudai, Oka, Miho, Miura, Masayuki, Ohata, Shinya, Katada, Toshiaki, Kontani, Kenji·2019·Genes to Cells
DOI 10.1111/gtc.12687
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Abstract

Lysosomes are acidic organelles responsible for degrading both exogenous and endogenous materials. The small GTPase Arl8 localizes primarily to lysosomes and is involved in lysosomal function. In the present study, using Arl8b gene‐trapped mutant (Arl8b−/−) mice, we show that Arl8b is required for the development of dorsal structures of the neural tube, including the thalamus and hippocampus. In embryonic day (E) 10.5 Arl8b−/− embryos, Sox1 (a neuroepithelium marker) was ectopically expressed in the roof plate, whereas the expression of Gdf7 and Msx1 (roof plate markers) was reduced in the dorsal midline of the midbrain. Ectopic expression of Sox1 in Arl8b−/− embryos was detected also at E9.0 in the neural fold, which gives rise to the roof plate. In addition, the levels of Bmp receptor IA and phosphorylated Smad 1/5/8 (downstream of BMP signaling) were increased in the neural fold of E9.0 Arl8b−/− embryos. These results suggest that Arl8b is involved in the development of the neural fold and the subsequently formed roof plate, possibly via control of BMP signaling.

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  • KO mice for the vast majority of genes that play fundamental roles in lysosomal positioning in both retrograde and anterograde directions are lethal or die immediately after birth.

    “KO mice for the vast majority of genes that play fundamental roles in this process, in both the retrograde and anterograde directions, are lethal or die immediately after birth.”

    From TMEM55B promotes anterograde transport and distal axonal distribution of LAMP1-positive organelles (2026) · cites this paper as Hashimoto et al., 2019

    Section 2.1 reports that Arl8b-null mice died around birth and links Arl8b to plus-end-directed trafficking of lysosome-associated vesicles. It does not establish that the vast majority of genes involved in lysosomal positioning cause lethality when knocked out, or report comparable outcomes for retrograde-positioning genes. No page number is given for the decisive passage in our copy. (LLM, conf=0.88)

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Metadata

Authors
Hashimoto, K., Yamaguchi, Y., Kishi, Y., Kikko, Y., Takasaki, K., Maeda, Y., Matsumoto, Y., Oka, M., Miura, M., Ohata, S., Katada, T., & Kontani, K.
Affiliations
  • Department of Physiological Chemistry, Graduate School of Pharmaceutical Sciences The University of Tokyo Tokyo Japan
  • Department of Genetics, Graduate School of Pharmaceutical Sciences The University of Tokyo Tokyo Japan
  • Laboratory of Molecular Biology, Graduate School of Pharmaceutical Sciences The University of Tokyo Tokyo Japan
ORCID
Venue
Genes to Cells
Publisher
Wiley
Published
2019-05-26
Volume
24
Issue
6
Pages
436-448
ISSN
  • 1356-9597
  • 1365-2443
DOI
10.1111/gtc.12687
Cited by
2
References
0
Language
en
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Funders
  • Japan Society for the Promotion of Science (JP14J12392, JP16H06163, JP15K06947, JP18K14622, JP16H06385, JP23229001, JP23370083, JP26291038)
  • Yasuda Memorial Medical Foundation
  • Japan Agency for Medical Research and Development (JP18gm5010001)
  • Ministry of Education, Culture, Sports, Science and Technology (JP26110005, JP23113706)

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