Cuervo R and Chimal-Monroy J (2013), Chemical activation of RARβ induces post-embryo...

XB-ART-47155

Sci Rep 2013 Jan 01;3:1886. doi: 10.1038/srep01886.

Show Gene links Show Anatomy links

Chemical activation of RARβ induces post-embryonically bilateral limb duplication during Xenopus limb regeneration.

Cuervo R , Chimal-Monroy J .

???displayArticle.abstract???
The anuran amphibian Xenopus laevis can regenerate its limbs for a limited time during the larval stage, while limbs are still developing. Using this regeneration model, we evaluated the proximo-distal blastema cell identity when endogenous retinoids were increased by CYP26 inhibition or when RAR-specific agonists altered RA signaling. Simultaneous proximo-distal and antero-posterior limb duplications were generated, and the RAR-specific agonist can modify blastema identity after amputation, because chemical activation of RARβ produced bilateral hindlimb duplications that resulted in a drastic duplication phenotype of regenerating limbs.

???displayArticle.pubmedLink??? 23703360
???displayArticle.pmcLink??? PMC3662968
???displayArticle.link??? Sci Rep

Species referenced: Xenopus laevis
Genes referenced: cyp26a1 rab40b rarb

Phenotypes: Xla Wt + AC55649 + hindlimb amputation (Fig2 B, B^1 B") [+]

???attribute.lit??? ???displayArticles.show???

	Figure 1. Duplication of hindlimb regenerates treated with CYP26 inhibitor.(A) Lateral view of Alcian blue and alizarin red-stained control hindlimb 30 days after amputation. Anterior is down. (B) Stage 62 metamorphic larva showing a complete P-D and A-P duplication. White arrow points to the secondary right pelvic bone from which emerges a twisted limb with mirror-image autopod duplication and taumelic long bones. Black arrowhead points to the original femur bone. (C) Other larvae showing complete duplicated limb with an autopod exhibiting A-P duplication included the tarsal bones (asterisk). Arrow points to the iliac shaft of the secondary pelvis and arrowhead points to the original femur bone. (D) Contra-lateral ectromelic hindlimbs showing what seem to be interdigital membranes (white arrowhead). (E, F) Hindlimbs of live froglets showing interdigital membranes. White arrowheads points to the presumptive interdigital membrane attached to distal region of an ectromelic hindlimb. is, iliac shaft., f, femur., tf, tibiofibula., t, tarsals., m, metatarsals., ph, phalanges.
	Figure 2. Bilateral limb duplication in regenerates treated with the RARβ agonist AC55649.(A) Ventro-lateral view of left hindlimb nine days post amputation treated AC55649. (A′) Closer view of the same hindlimb showed in (A). Black arrowheads point to the amputation plane. (B, B′, B”) Lateral, ventral and contralateral view respectively of B-L duplicated at 16 days post-amputation and stained with Alcian blue. Black arrow points to the hypomorphic contralateral hindlimb. (C) Ventro-lateral view of B-L duplicated hindlimb of stage 62 Alcian blue and alizarin red-stained larva. (D) Closer view of the same duplicate partially dissected. (E) Dorsal view of dissected duplicate; compare the primary pelvis (right) and secondary pelvis (left) dorsally attached to the original femur bone. (F) Posterior view of limbs showing the bifurcated femoral blood vessel. Arrowhead points to the well-developed secondary iliac shafts. (G) Closer view of the bifurcated blood vessel. (H) Histology of duplicates at twelve days after amputation stained with safranine-O. Arrowhead points to the femur bone from which duplicated limbs emerge. No notochord cells are observed. Scale bar 200 μm.
	Figure 3. Schematized comparative of axes in normal regeneration and B-L duplication.(A) Normally the blastema places the proximo-distal axis accordingly with the level of amputation (red dotted line), maintaining the antero-posterior and dorso-ventral axes unaltered. (B) However, the blastema is competent to form bilateral limbs by reestablishing the most proximal position of hindlimbs (i.e. the dorsal part of a new pelvis). Hence in this blastema a new dorso-ventral axis forms (blue dotted line) and the left-right axis (cyan dotted line) emerges from the crossroad with the antero-posterior axis (green dotted line). a, anterior; p, posterior; dr, dorsal; v, ventral; px, proximal; d, distal; l, left; r, right.

References [+] :

Abu-Abed, Mouse P450RAI (CYP26) expression and retinoic acid-inducible retinoic acid metabolism in F9 cells are regulated by retinoic acid receptor gamma and retinoid X receptor alpha. 1998, Pubmed