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


CONCLUSIONS
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.
Negishi
Takahiro
T
Department of Developmental and Regenerative Biology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.
Nagai
Yoko
Y
Asaoka
Yoichi
Y
Ohno
Mami
M
Namae
Misako
M
Mitani
Hiroshi
H
Sasaki
Takashi
T
Shimizu
Nobuyoshi
N
Terai
Shuji
S
Sakaida
Isao
I
Kondoh
Hisato
H
Katada
Toshiaki
T
Furutani-Seiki
Makoto
M
Nishina
Hiroshi
H
D000818:Animals; D019521:Body Patterning / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D008099:Liver / Q000196:embryology*; D009990:Oryzias / Q000235:genetics*; D015398:Signal Transduction; D014212:Tretinoin / Q000502:physiology*; D051154:Wnt2 Protein / Q000235:genetics*
D051154:Wnt2 Protein; D014212:Tretinoin