Retinoic acid signaling positively regulates liver specification by inducing wnt2bb gene expression in medaka

Takahiro Negishi, Yoko Nagai, Yoichi Asaoka, Mami Ohno, Misako Namae, Hiroshi Mitani, Takashi Sasaki, Nobuyoshi Shimizu, Shuji Terai, Isao Sakaida, Hisato Kondoh, Toshiaki Katada, Makoto Furutani-Seiki, Hiroshi Nishina

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

During vertebrate embryogenesis, the liver develops at a precise location along the endodermal primitive gut tube because of signaling delivered by adjacent mesodermal tissues. Although several signaling molecules have been associated with liver formation, the molecular mechanism that regulates liver specification is still unclear. We previously performed a screen in medaka to isolate mutants with impaired liver development. The medaka hio mutants exhibit a profound (but transient) defect in liver specification that resembles the liver formation defect found in zebrafish prometheus (prt) mutants, whose mutation occurs in the wnt2bb gene. In addition to their liver abnormality, hio mutants lack pectoral fins and die after hatching. Positional cloning indicated that the hio mutation affects the raldh2 gene encoding retinaldehyde dehydrogenase type2 (RALDH2), the enzyme principally responsible for retinoic acid (RA) biosynthesis. Mutations of raldh2 in zebrafish preclude the development of pectoral fins. Interestingly, in hio mutants, expression of wnt2bb in the lateral plate mesoderm (LPM) directly adjacent to the liver-forming endoderm was completely lost. Conclusion: Our data reveal the unexpected finding that RA signaling positively regulates the wnt2bb gene expression required for liver specification in medaka. These results suggest that a common molecular mechanism may underlie liver and pectoral fin specification during piscine embryogenesis.

Original languageEnglish
Pages (from-to)1037-1045
Number of pages9
JournalHepatology
Volume51
Issue number3
DOIs
Publication statusPublished - 2010 Mar

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Oryzias
Tretinoin
Gene Expression
Liver
Zebrafish
Mutation
Embryonic Development
Retinaldehyde
Gastrula
Endoderm
Mesoderm
Genes
Vertebrates
Organism Cloning
Oxidoreductases

ASJC Scopus subject areas

  • Hepatology

Cite this

Negishi, T., Nagai, Y., Asaoka, Y., Ohno, M., Namae, M., Mitani, H., ... Nishina, H. (2010). Retinoic acid signaling positively regulates liver specification by inducing wnt2bb gene expression in medaka. Hepatology, 51(3), 1037-1045. https://doi.org/10.1002/hep.23387

Retinoic acid signaling positively regulates liver specification by inducing wnt2bb gene expression in medaka. / Negishi, Takahiro; Nagai, Yoko; Asaoka, Yoichi; Ohno, Mami; Namae, Misako; Mitani, Hiroshi; Sasaki, Takashi; Shimizu, Nobuyoshi; Terai, Shuji; Sakaida, Isao; Kondoh, Hisato; Katada, Toshiaki; Furutani-Seiki, Makoto; Nishina, Hiroshi.

In: Hepatology, Vol. 51, No. 3, 03.2010, p. 1037-1045.

Research output: Contribution to journalArticle

Negishi, T, Nagai, Y, Asaoka, Y, Ohno, M, Namae, M, Mitani, H, Sasaki, T, Shimizu, N, Terai, S, Sakaida, I, Kondoh, H, Katada, T, Furutani-Seiki, M & Nishina, H 2010, 'Retinoic acid signaling positively regulates liver specification by inducing wnt2bb gene expression in medaka', Hepatology, vol. 51, no. 3, pp. 1037-1045. https://doi.org/10.1002/hep.23387
Negishi, Takahiro ; Nagai, Yoko ; Asaoka, Yoichi ; Ohno, Mami ; Namae, Misako ; Mitani, Hiroshi ; Sasaki, Takashi ; Shimizu, Nobuyoshi ; Terai, Shuji ; Sakaida, Isao ; Kondoh, Hisato ; Katada, Toshiaki ; Furutani-Seiki, Makoto ; Nishina, Hiroshi. / Retinoic acid signaling positively regulates liver specification by inducing wnt2bb gene expression in medaka. In: Hepatology. 2010 ; Vol. 51, No. 3. pp. 1037-1045.
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