Many of the genes involved in the initial development of the limb in higher vertebrates are also expressed during regeneration of the limb in urodeles such as Notophthalmus viridescens. These similarities have led researchers to conclude that the regeneration process is a recapitulation of development, and that patterning of the regenerate mimics pattern formation in development. However, the developing limb and the regenerating limb do not look similar. In developing urodele forelimbs, digits appear sequentially as outgrowths from the limb palette. In regeneration, all the digits appear at once. In this work, we address the issue of whether regeneration and development are similar by examining growth and apoptosis patterns. In contrast to higher vertebrates, forelimb development in the newt, N. viridescens, does not use interdigital apoptosis as the method of digit separation. During adult forelimb regeneration, apoptosis seems to play an important role in wound healing and again during cartilage to bone turnover in the advanced digits and radius/ulna. However, similar to forelimb development, demarcation of the digits in adult forelimb regeneration does not involve interdigital apoptosis. Outgrowth, rather than regression of the interdigital mesenchyme, leads to the individualization of forelimb digits in both newt development and regeneration.
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We thank Adam Baker for technical expertise, help with the figures, and critical reading of the manuscript. We thank Sandy Vascotto and Richard A. Liversage for helpful discussions. This work was supported by the Natural Sciences and Engineering Council of Canada (C.T.) and by the Canadian Institutes of Health Research (C.T.).
Edited by R.P. Elinson
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Vlaskalin, T., Wong, C.J. & Tsilfidis, C. Growth and apoptosis during larval forelimb development and adult forelimb regeneration in the newt (Notophthalmus viridescens). Dev Genes Evol 214, 423–431 (2004). https://doi.org/10.1007/s00427-004-0417-1
- Forelimb development
- Forelimb regeneration