Limb regeneration is a well studied field in developmental biology and amphibians such as the newt provide classic model systems for investigators. However, there is a major gap in our understanding of the signal control networks and critical control proteins responsible for orchestrating tissue regeneration in the growing limb following amputation. In this study, we have measured newt (N. viridescens) gene expression levels for ˜1200 selected genes important in tissue regeneration at various times post-amputation (days 1,3,6,12 and 21) at 6 different limb amputation sites [proximal (upper) and distal (lower) positions of forelimb, hindlimb and tail]. Custom designed Agilent chips were used containing 23 replicates per gene allowing for high statistical significance in the individual measured gene expression levels. Here we provide analyses of the microarray data that demonstrate a global gene expression correlation decrease on going from proximal to distal amputation sites of either limb or tail appendages. Also, the proximal (upper) forelimb and hindlimb regenerates have by far the most highly pairwise correlated gene expression levels of all sites. In contrast, the distal (lower) forelimb and hindlimb and tail regenerates reveal the least pairwise correlated gene expression levels. In the case of many individual genes (e.g. MMP3), similar amputation site position correlation results are exhibited to that of the global gene view. These data support the idea that limb loss at a proximal site produces a far more robust response as compared to a more distal site and requires a greater level of gene regulation to properly rebuild the lost structure.

Project support is acknowledged from DARPA.

References and Footnotes

1. K.A. Marx, J. Sharko, G.G. Grinstein, S. Odelberg and H.G. Simon, IEEE Proceedings 7th BIBE, 456-463 (2007).


2. J. Sharko, G.G. Grinstein K.A. Marx, J. Zhou, C.H. Cheng, S. Odelberg and H.G. Simon, 11th Int?l Conf. Information Visualization, IEEE Computer Society, Wash, D.C. 521-526 (2007).