Pattern formation is the process that controls the spatial ordering of organs and differentiated cell types during development. Features of the mechanism of pattern formation are revealed when developing systems undergo pattern regulation. Developing and regenerating limbs show extensive regulative abilities and thus have long been used as models for pattern formation in vertebrates. The proposed experiments on regenerating axolotl limbs use a combination of in vivo and invitor approaches to investigate the ability of cells form one limb position to induce patterning and growth responses in cells at a different position. The induction of supernumerary pattern and growth will be used to investigate whether limb cells retain their positional properties in vitro, and whether the molecules associated with these properties can be detected in membranes, extracellular matrix or culture medium conditioned by cells from particular limb positions. We will examine the ability of retinoic acid to change anterior limb cells that function as posterior cells using both in vivo and in vitro approaches. Finally, the effects of TGF beta and a and b FGF, which have known effects on limb development, will be investigated for their role in pattern formation and position-dependent growth. It is anticipated that an understanding of pattern formation will allow for the development of strategies to stimulate controlled growth and pattern (regeneration); to inhibit unpatterned, uncontrolled growth (cancer) and to correct abnormal pattern (birth defects).

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD025620-02
Application #
3326804
Study Section
Cellular Biology and Physiology Subcommittee 1 (CBY)
Project Start
1990-05-01
Project End
1995-04-30
Budget Start
1991-05-01
Budget End
1992-04-30
Support Year
2
Fiscal Year
1991
Total Cost
Indirect Cost
Name
University of California Irvine
Department
Type
Schools of Arts and Sciences
DUNS #
161202122
City
Irvine
State
CA
Country
United States
Zip Code
92697
Gardiner, D M; Carlson, M R; Roy, S (1999) Towards a functional analysis of limb regeneration. Semin Cell Dev Biol 10:385-93
Yang, E V; Gardiner, D M; Carlson, M R et al. (1999) Expression of Mmp-9 and related matrix metalloproteinase genes during axolotl limb regeneration. Dev Dyn 216:2-9
Mullen, L M; Bryant, S V; Torok, M A et al. (1996) Nerve dependency of regeneration: the role of Distal-less and FGF signaling in amphibian limb regeneration. Development 122:3487-97
Selleck, M A; Hayamizu, T F; Ohsugi, K et al. (1996) Digit induction by Hensen's node and notochord involves the expression of shh but not RAR-beta 2. Dev Biol 173:318-26
Gardiner, D M; Blumberg, B; Komine, Y et al. (1995) Regulation of HoxA expression in developing and regenerating axolotl limbs. Development 121:1731-41
Hayamizu, T F; Wanek, N; Taylor, G et al. (1994) Regeneration of HoxD expression domains during pattern regulation in chick wing buds. Dev Biol 161:504-12
Hayamizu, T F; Bryant, S V (1994) Reciprocal changes in Hox D13 and RAR-beta 2 expression in response to retinoic acid in chick limb buds. Dev Biol 166:123-32