Chemical activation of Wnt/β-catenin signalling inhibits innervation and causes skeletal tissue malformations during axolotl limb regeneration.
Limb regeneration involves several interrelated physiological processes in which a particular signalling pathway may play a variety of functions. Blocking the function of Wnt/β-catenin signalling during limb regeneration inhibits regeneration in axolotls (Ambystoma mexicanum). Limb development shares many features with limb regeneration, and Wnt/β-catenin activation has different effects depending on the developmental stage. The aim of this study was to evaluate whether Wnt/β-catenin signalling activation during axolotl limb regeneration has different effects when activated at different stages of regeneration. To evaluate this hypothesis, we treated amputated axolotls with a Wnt agonist chemical at different stages of limb regeneration. The results showed that limb regeneration was inhibited when the treatment began before blastema formation. Under these conditions, blastema formation was hindered, possibly due to the lack of innervation. On the other hand, when axolotls were treated after blastema formation and immediately before the onset of morphogenesis, we observed structural disorganization in skeletal formation. In conclusion, we found that limb regeneration was differentially affected depending on the stage at which the Wnt signalling pathway was activated.
Departamento de Medicina Genómica y Toxicología Ambiental, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Ciudad Universitaria, Mexico DF 04510, Mexico.
Sabina
S
Wischin
Departamento de Bioquímica, Facultad de Medicina, Universidad Nacional Autónoma de México, Ciudad Universitaria, Mexico DF 04510, Mexico.
Cristina
C
Castañeda-Patlán
Departamento de Bioquímica, Facultad de Medicina, Universidad Nacional Autónoma de México, Ciudad Universitaria, Mexico DF 04510, Mexico.
Martha
M
Robles-Flores
Departamento de Medicina Genómica y Toxicología Ambiental, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Ciudad Universitaria, Mexico DF 04510, Mexico. Electronic address: jchimal@unam.mx.
Jesús
J
Chimal-Monroy
D000558:Ambystoma mexicanum; D000672:Amputation Stumps / Q000294:innervation* / Q000503:physiopathology; D000818:Animals; D052117:Benzodioxoles / Q000494:pharmacology; D049109:Cell Proliferation; D011743:Pyrimidines / Q000494:pharmacology; D012038:Regeneration; D055758:SOX9 Transcription Factor / Q000378:metabolism; D060449:Wnt Signaling Pathway / Q000187:drug effects*
C581356:2-amino-4-(3,4-(methylenedioxy)benzylamino)-6-(3-methoxyphenyl)pyrimidine; D052117:Benzodioxoles; D011743:Pyrimidines; D055758:SOX9 Transcription Factor
Axolotl; Limb regeneration; Wnt/β-catenin signalling activation