Proximodistal identity during vertebrate limb regeneration is regulated by Meis homeodomain proteins

• Published in: Development (Cambridge) Vol. 132; no. 18; pp. 4131 - 4142
• Main Authors: Mercader, Nadia, Tanaka, Elly M, Torres, Miguel
• Format: Journal Article
• Language: English
• Published: England The Company of Biologists Limited 01.09.2005
• Subjects: Ambystoma mexicanum - physiology; Amputation, Surgical; Animals; Blotting, Western; Cloning, Molecular; DNA Primers; DNA-Binding Proteins - genetics; Electroporation; Forelimb - physiology; Gene Expression Regulation; Homeodomain Proteins - genetics; Homeodomain Proteins - metabolism; Immunohistochemistry; In Situ Hybridization; Myeloid Ecotropic Viral Integration Site 1 Protein; Neoplasm Proteins - genetics; Neoplasm Proteins - metabolism; Pre-B-Cell Leukemia Transcription Factor 1; Proto-Oncogene Proteins - genetics; Regeneration - physiology; Reverse Transcriptase Polymerase Chain Reaction; Tretinoin - metabolism; Urodela
• ISSN: 0950-1991; 1477-9129
• DOI: 10.1242/dev.01976

The mechanisms by which cells obtain instructions to precisely re-create the missing parts of an organ remain an unresolved question in regenerative biology. Urodele limb regeneration is a powerful model in which to study these mechanisms. Following limb amputation, blastema cells interpret the proximal-most positional identity in the stump to reproduce missing parts faithfully. Classical experiments showed the ability of retinoic acid (RA) to proximalize blastema positional values. Meis homeobox genes are involved in RA-dependent specification of proximal cell identity during limb development. To understand the molecular basis for specifying proximal positional identities during regeneration, we isolated the axolotl Meis homeobox family. Axolotl Meis genes are RA-regulated during both regeneration and embryonic limb development. During limb regeneration, Meis overexpression relocates distal blastema cells to more proximal locations, whereas Meis knockdown inhibits RA proximalization of limb blastemas. Meis genes are thus crucial targets of RA proximalizing activity on blastema cells.