|
|
|
|
|
|
|
||||
| Home Help Feedback Subscriptions Archive Search Table of Contents | ||||
Development, Vol 122, Issue 11 3487-3497, Copyright © 1996 by Company of Biologists
JOURNAL ARTICLES |
LM Mullen, SV Bryant, MA Torok, B Blumberg and DM Gardiner
Department of Developmental and Cell Biology, University of California Irvine 92697-2275, USA.
Dlx-3, a homolog of Drosophila Dll, has been isolated from an axolotl blastema cDNA library, and its expression in developing and regenerating limbs characterized. The normal expression pattern, and the changes that occur during experimental treatments, indicate a correlation between Dlx-3 expression and the establishment of the outgrowth-permitting epidermis. Dlx-3 is expressed at high levels in a distal-to-proximal gradient in the epidermis of developing limb buds, and is upregulated in the apical ectodermal cap (AEC) during limb regeneration. Expression is maximal at the late bud stage of regeneration, coincident with the transition from the early phase of nerve dependency to the later phase of nerve independence. Dlx-3 expression in the epidermis is rapidly downregulated by denervation during the nerve-dependent phase and is unaffected by denervation during the nerve-independent phase. We investigated this relationship between nerves and Dlx-3 expression by implanting FGF-2 beads into regenerates that had been denervated at a nerve-dependent stage. Dlx-3 expression was maintained by FGF-2 after denervation, and regeneration progressed to completion. In addition, we detected FGF-2 protein in the AEC and in nerves, and observed that the level of expression in both tissues decreases dramatically in response to denervation. We conclude that both limb development and regeneration require a permissive epidermis, characterized by Dlx-3 and FGF expression, both of which are maintained by FGF through an autocrine loop. The transformation of the limb epidermis into a functional AEC that produces and responds to FGF autocatalytically, is presumed to be induced by FGF. Since nerves appear to be a source of this priming FGF, it is possible that a member of the FGF family of growth factors is the elusive neurotrophic factor of limb regeneration.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati 
Twitter What's this?
This article has been cited by other articles:
|
|
 |
|
  A. Satoh, M. A. James, and D. M. Gardiner The Role of Nerve Signaling in Limb Genesis and Agenesis During Axolotl Limb Regeneration J. Bone Joint Surg. Am., July 1, 2009; 91(Supplement_4): 90 - 98. [Full Text] [PDF]
|
|
|
|
 |
|
 M. Kragl, D. Knapp, E. Nacu, S. Khattak, E. Schnapp, H.-H. Epperlein, and E.M. Tanaka Novel Insights into the Flexibility of Cell and Positional Identity during Urodele Limb Regeneration Cold Spring Harb Symp Quant Biol, November 26, 2008; (2008) sqb.2008.73.034v2. [Abstract] [PDF]
|
|
|
|
 |
|
 A. Kumar, J. W. Godwin, P. B. Gates, A. A. Garza-Garcia, and J. P. Brockes Molecular Basis for the Nerve Dependence of Limb Regeneration in an Adult Vertebrate Science, November 2, 2007; 318(5851): 772 - 777. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. L. Stoick-Cooper, R. T. Moon, and G. Weidinger Advances in signaling in vertebrate regeneration as a prelude to regenerative medicine Genes & Dev., June 1, 2007; 21(11): 1292 - 1315. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Hara, S. Samuel, J. Liu, D. Rosen, R. R. Langley, and H. Naora A Homeobox Gene Related to Drosophila Distal-Less Promotes Ovarian Tumorigenicity by Inducing Expression of Vascular Endothelial Growth Factor and Fibroblast Growth Factor-2 Am. J. Pathol., May 1, 2007; 170(5): 1594 - 1606. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. P. Brockes and A. Kumar Appendage Regeneration in Adult Vertebrates and Implications for Regenerative Medicine Science, December 23, 2005; 310(5756): 1919 - 1923. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Panganiban and J. L. R. Rubenstein Developmental functions of the Distal-less/Dlx homeobox genes Development, January 10, 2002; 129(19): 4371 - 4386. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Launay, J.-M. Cabelguen, J.-F. Marini, and C. Chanoine Effects of locomotor training on hindlimb regeneration in the urodele amphibian Pleurodeles waltlii J. Physiol., August 15, 2001; 535(1): 241 - 248. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. M. Hopkins Limb Regeneration in the Fiddler Crab, Uca pugilator: Hormonal and Growth Factor Control Integr. Comp. Biol., June 1, 2001; 41(3): 389 - 398. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K Kato, H Orii, K Watanabe, and K Agata The role of dorsoventral interaction in the onset of planarian regeneration Development, January 2, 1999; 126(5): 1031 - 1040. [Abstract] [PDF]
|
|
