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Molecular and cellular differentiation of muscle, cartilage and bone in the developing limb
Symposium 6: Cell Differentiation During Development (369-373)
37O
369
MOLECULARAND CELLULARDIFFERENTIATIONOF MUSCLE, CARTILAGE AND BONE IN THE DEVELOPING LIMB. Arnold I. Caplan,
C E L L U L A R A N D M O L E C U L A R S T U D I E S OF E A R L Y EVENTS IN A M P H I B I A N LIMB R E G E N E R A T I O N . J.P. Brockes. MRC Cell B i o p h y s i c s Unit, 26-29 D r u r y Lane, L o n d o n W C 2 B 5RL, England. A f t e r a m p u t a t i o n of a limb in U r o d e l e A m p h i b i a n s , the p r o g e n i t o r cells of the regenerate, termed b l a s t e m a l cells, a r i s e locally. A m o n o c l o n a l antibody, t e r m e d 22/18, has p r o v i d e d e v i d e n c e a b o u t the o r i g i n of a m a j o r p o p u l a t i o n of cells in the e a r l y blastema, and identifies cells w h o s e division- as a s s a y e d by the t h y m i d i n e l a b e l l i n g index, is d e p e n d ent on the nerve supply 1,2. This is c o n s i d e r e d to r e f l e c t the a c t i v i t y of one or more m i t o g e n i c f a c t o r s p r o v i d e d by the nerve, but the m o l e c u l a r i d e n t i t y of t h e s e f a c t o r s remains uncertain. One c a n d i d a t e is Glial G r o w t h F a c t o r (GGF) a m o l e c u l e i d e n t i f i e d bY v i r t u e of its e f f e c t on c u l t u r e d rat S c h w a n n cells, and p u r i f i e d to a p p a r e n t h o m o g e n e i t y from the b o v i n e p i t u i t a r y 3. GGF is p r e s e n t in the newt blastema, is lost on d e n e r v a t i o n , and acts to stimL11ate DNA s y n t h e s i s in 22/18 p o s i t i v e cells in the d e n e r v a t e d blastema, i. C.R. ~ J n t n e r & J.P. Brockes, N a t u r e 308, 67 (i~84). 2. J.P. Brockes, S c i e n c e 225, 1280 (iC84).3. G.E. Lemke & J.P. Brockes, J. N e u r o s c i 4, 75
Biology Department, Case Western Reserve University, Cleveland, Ohio 44106, U.S.A. The mesenchymal cells of the avian limb differentiate into a variety of phenotypes including cartilage, muscle and bone. These complex events are regulated by the interplay between intrinsic, self-assembly properties o---f ~ual cells and extrinsic cuing which establishes the physical and developmental position of the cells. The developing tissues undergo a program of orderly replacement events wherein one family of molecules or cells is supplanted by the next group of molecules or cells. The molecular and cellular variants involved in these replacement events are similar but distinct and are called ISOFORMS. The programmed appearance of these isoforms continues f r o m early embryology into senescence. The detailed structure of cartilage and muscle proteoglycans will be used as examples of molecular isoforms, since the synthesis of thes e macromolecules follows two different patterns. Isoformic transitions form a conceptual context for understanding both morphogenesis and aging. 151S
37O
369
MOLECULARAND CELLULARDIFFERENTIATIONOF MUSCLE, CARTILAGE AND BONE IN THE DEVELOPING LIMB. Arnold I. Caplan,
C E L L U L A R A N D M O L E C U L A R S T U D I E S OF E A R L Y EVENTS IN A M P H I B I A N LIMB R E G E N E R A T I O N . J.P. Brockes. MRC Cell B i o p h y s i c s Unit, 26-29 D r u r y Lane, L o n d o n W C 2 B 5RL, England. A f t e r a m p u t a t i o n of a limb in U r o d e l e A m p h i b i a n s , the p r o g e n i t o r cells of the regenerate, termed b l a s t e m a l cells, a r i s e locally. A m o n o c l o n a l antibody, t e r m e d 22/18, has p r o v i d e d e v i d e n c e a b o u t the o r i g i n of a m a j o r p o p u l a t i o n of cells in the e a r l y blastema, and identifies cells w h o s e division- as a s s a y e d by the t h y m i d i n e l a b e l l i n g index, is d e p e n d ent on the nerve supply 1,2. This is c o n s i d e r e d to r e f l e c t the a c t i v i t y of one or more m i t o g e n i c f a c t o r s p r o v i d e d by the nerve, but the m o l e c u l a r i d e n t i t y of t h e s e f a c t o r s remains uncertain. One c a n d i d a t e is Glial G r o w t h F a c t o r (GGF) a m o l e c u l e i d e n t i f i e d bY v i r t u e of its e f f e c t on c u l t u r e d rat S c h w a n n cells, and p u r i f i e d to a p p a r e n t h o m o g e n e i t y from the b o v i n e p i t u i t a r y 3. GGF is p r e s e n t in the newt blastema, is lost on d e n e r v a t i o n , and acts to stimL11ate DNA s y n t h e s i s in 22/18 p o s i t i v e cells in the d e n e r v a t e d blastema, i. C.R. ~ J n t n e r & J.P. Brockes, N a t u r e 308, 67 (i~84). 2. J.P. Brockes, S c i e n c e 225, 1280 (iC84).3. G.E. Lemke & J.P. Brockes, J. N e u r o s c i 4, 75
Biology Department, Case Western Reserve University, Cleveland, Ohio 44106, U.S.A. The mesenchymal cells of the avian limb differentiate into a variety of phenotypes including cartilage, muscle and bone. These complex events are regulated by the interplay between intrinsic, self-assembly properties o---f ~ual cells and extrinsic cuing which establishes the physical and developmental position of the cells. The developing tissues undergo a program of orderly replacement events wherein one family of molecules or cells is supplanted by the next group of molecules or cells. The molecular and cellular variants involved in these replacement events are similar but distinct and are called ISOFORMS. The programmed appearance of these isoforms continues f r o m early embryology into senescence. The detailed structure of cartilage and muscle proteoglycans will be used as examples of molecular isoforms, since the synthesis of thes e macromolecules follows two different patterns. Isoformic transitions form a conceptual context for understanding both morphogenesis and aging. 151S