BMP inhibition-driven regulation of six-3 underlies induction of newt lens regeneration.
Lens regeneration in adult newts is a classic example of how cells can faithfully regenerate a complete organ through the process of transdifferentiation. After lens removal, the pigment epithelial cells of the dorsal, but not the ventral, iris dedifferentiate and then differentiate to form a new lens. Understanding how this process is regulated might provide clues about why lens regeneration does not occur in higher vertebrates. The genes six-3 and pax-6 are known to induce ectopic lenses during embryogenesis. Here we tested these genes, as well as members of the bone morphogenetic protein (BMP) pathway that regulate establishment of the dorsal-ventral axis in embryos, for their ability to induce lens regeneration. We show that the lens can be regenerated from the ventral iris when the BMP pathway is inhibited and when the iris is transfected with six-3 and treated with retinoic acid. In intact irises, six-3 is expressed at higher levels in the ventral than in the dorsal iris. During regeneration, however, only expression in the dorsal iris is significantly increased. Such an increase is seen in ventral irises only when they are induced to transdifferentiate by six-3 and retinoic acid or by BMP inhibitors. These data suggest that lens regeneration can be achieved in noncompetent adult tissues and that this regeneration occurs through a gene regulatory mechanism that is more complex than the dorsal expression of lens regeneration-specific genes.
Grogg
Matthew W
MW
Laboratory of Molecular Biology, Department of Biology, University of Dayton, Dayton, Ohio 45469-2320, USA.
Call
Mindy K
MK
Okamoto
Mitsumasa
M
Vergara
M Natalia
MN
Del Rio-Tsonis
Katia
K
Tsonis
Panagiotis A
PA
D000557:Ambystoma; D000818:Animals; D052005:Bone Morphogenetic Protein Receptors, Type I / Q000235:genetics / Q000378:metabolism; D019485:Bone Morphogenetic Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D007498:Iris / Q000166:cytology / Q000187:drug effects / Q000254:growth & development / Q000502:physiology; D007908:Lens, Crystalline / Q000166:cytology / Q000187:drug effects / Q000254:growth & development / Q000502:physiology*; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics / Q000378:metabolism; D010857:Pigment Epithelium of Eye / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D012038:Regeneration / Q000187:drug effects / Q000502:physiology*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D012455:Salamandridae / Q000235:genetics / Q000502:physiology*; D014212:Tretinoin / Q000494:pharmacology; D000097607:Homeobox Protein SIX3
D052005:Bone Morphogenetic Protein Receptors, Type I; D019485:Bone Morphogenetic Proteins; D005136:Eye Proteins; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; D012097:Repressor Proteins; D014212:Tretinoin; D000097607:Homeobox Protein SIX3