Fig. 4. Abnormal patterns of Fgf expression in the Raldh2^–/– forelimbs. (A) Comparative view of E9.5 wild-type (left) and Raldh2^–/– embryos treated with RA from E7.5 to E8.5. Note comparable expression levels in various expression domains, except in forelimb ectoderm. br, branchial arches; flb, forelimb buds; mhb, mid-hindbrain region; tb, tail bud. (B,C) Details of Fgf8 expression in the forelimb ectoderm of E9.5 wild-type (B) and Raldh2^–/– (C) embryos after RA supplementation from E7.5-8.5. (D) Fgf8 expression pattern in an E10.5 wild-type forelimb AER. (E-H) Altered patterns of Fgf8 expression and AER morphology in E10.5 Raldh2^–/– forelimbs, after RA treatment from E7.5 to E9.5 (250 µg/g). (I-K) Fgf10 expression in the distal mesoderm of E10.5 wild-type (I) and Raldh2^–/– (J,K) forelimbs. Whereas Fgf10 is expressed throughout the distal mesoderm in (I), a preferential anterior distribution is seen in (J) and an abnormal anterior tissue outgrowth with specific Fgf10 expression is found in (K). (L-N) Fgf4 expression in wild-type (L) and Raldh2^–/– (M,N) E10.5 forelimb buds. Fgf4 is expressed in the posterior two-thirds of the AER in wild type. No expression is detectable in the bud in M, whereas the one in N shows an ectopic patch of expression in the anterior part of the AER.

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