DNA SYNTHESIS IN RANA PIPIENS TADPOLE LIVER DURING TRIIODOTHYRONINE-INDUCED METAMORPHOSIS1

The relationship of DNA synthesis and cellular turnover to biochemical differentiation during Ts-induced metamorphosis of R. pipiens liver was investigated. Rates of DNA synthesis were estimated by rates of 3 H-thymidine incorporation into the acid-precipitable fractions, corrected for both precursor uptake into the acid-soluble pool, and for endogenous thymine pool size. During T3 -induced metamorphosis, periods of DNA synthesis and fluctuations in DNA content preceded expression of biochemical differentiation as measured by the enzyme arginase, and fluctuations in synthesis rates preceded corresponding fluctuations in content. The earliest response to T3- , was a 50% decrease in liver DNA, followed by increases in thymidine incorporation at 16 hr, 2 days, and 5-8 days. The size of the endogenous thymine pool was not significantly altered by T3 These results indicate that both DNA synthesis and cellular turnover play a significant role in determining net DNA synthetic rates and content during metamorphosis. Expression of thyroxin-induced development of the tadpole liver appears to be associated with both proliferation and cellular death, and metamorphosis of the liver cannot be occurring in a “fixed population of cells.”     

DNA SYNTHESIS AND CELL TURNOVER IN RANA PIPIENS TADPOLE LIVER DURING SPONTANEOUS METAMORPHOSIS1

The relationship of DNA synthesis and cellular turnover to biochemical differentiation during metamorphosis of R. pipiens liver was investigated. Average DNA/cell was constant at 11.6 pg/ nucleus through stage XXV; but increased during juvenile growth; during metamorphosis stages, changes in total DNA content must correspond to changes in cell number. Rates of DNA synthesis were estimated by rates of ³H-thymidine incorporated into the acid-precipitable fractions, corrected for both precursor uptake into the acid-soluble pool, and for endogenous thymine pool size. DNA content increased steadily from premetamorphosis until late prometamorphosis; at preclimax stages XVIII and XX there were two successive decreases in DNA content of approximately 30%. Fluctuations in synthesis rates preceded corresponding fluctuations in content; DNA synthesis was maximal at stages XVI and XVIII, decreased nearly ten-fold at metamorphic climax, and then gradually rose again during late climax stages. The size of the endogenous thymine pool increased transitorily during spontaneous metamorphosis corresponding to a stage of maximal DNA synthesis. These results indicate that both DNA synthesis and cellular turnover play a significant role in determining net DNA synthesis rates and content during metamorphosis. Metamorphosis of the tadpole liver appears to be associated with both proliferation and cellular death, perhaps a replacement of “larval” by “adult” cells. Metamorphosis of the liver cannot be occuring in a “fixed population of cells” as is commonly assumed. An interpretation of the population dynamics of the metamorphic liver is presented.     

Developmental Plasticity: Developmental Conversion versus Phenotypic Modulation

The developmental mechanisms by which the environment may alterthe phenotype during development are reviewed. Developmentalplasticity may be of two forms: developmental conversion orphenotypic modulation. In developmental conversion, organismsuse specific environmental cues to activate alternative geneticprograms controlling development. These alternative programsmay either lead to alternative morphs, or may lead to the decisionto activate a developmental arrest. In phenotypic modulation,nonspecific phenotypic variation results from environmentalinfluences on rates or degrees of expression of the developmentalprogram, but the genetic programs controlling development arenot altered. Modulation, which is not necessarily adaptive,is probably the common form of environmentally induced phenotypicvariation in higher organisms, and adaptiveness of phenotypicplasticity therefore cannot be assumed unless specific geneticmechanisms can be demonstrated. The genetic mechanisms by whichdevelopmental plasticity may evolve are reviewed, and the relationshipbetween developmental plasticity and evolutionary plasticityare examined.