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Retinoic acid gives limb development a hand
Author(s) -
Duester Gregg,
Zhao Xianling
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.230.3
Subject(s) - forelimb , mesoderm , lateral plate mesoderm , hindlimb , retinoic acid , biology , limb development , anatomy , limb bud , microbiology and biotechnology , embryonic stem cell , embryo , genetics , gene
Retinoic acid (RA) signaling has been suggested to play an essential role during induction and patterning of both forelimb and hindlimb buds. Here, we utilize Raldh2−/− and Raldh3−/− mouse embryos lacking RA synthesis to demonstrate that RA is not required for hindlimb induction or patterning, but that RA is required for forelimb induction. RA generated by Raldh2 in somitic mesoderm acts as a proximal source of RA required during forelimb induction, but RA signaling in limb mesoderm itself is not required. Under conditions in which RA activity is absent in mesoderm during limb induction, genes required for limb induction and patterning are induced in both forelimbs and hindlimbs. RA action outside the limb field is sufficient for mesodermal induction of Tbx5 in the forelimb field, suggesting that RA reduces expression of a diffusible forelimb inhibitor produced in nearby tissues during the stage when forelimb induction occurs. As one example of this mechanism we demonstrate that RA signaling functions to repress Fgf8 expression in the intermediate mesoderm adjacent to the forelimb field. Thus, rather than playing an instructive role in forelimb and hindlimb mesoderm, our findings indicate that endogenous RA plays a forelimb‐specific permissive role via its action on tissues situated outside the forelimb field that influence limb induction but not patterning. Supported by NIH grant GM62848.