TRODUCTION Lug That adult marine invertebrates can concentrate amino acids irom a dilute solution has now been demonstrated for several dif- ferent organisms (Stephens and Schinske, 1961; Stephens, 1963, 1961: Ferguson, 1967). Recent studies have shown that sea urchin embryos can likewise transport exogenous amino acid and incorporate it in- to their protein (Mitchison and Cummins, 1966; Epel, 1967) and that there is an increased rate of both uptake and incorporation follow- ing fertilization (Hultin, 1953; Gross, 1961; Epel, 1967). In these eggs the incorporation(peaks) at the mid-gastrula stage and e subsequently decreases (Guidice, Vittorelli and Monroy, 1962). Little data is available, however, on rates of protein synthesis in the later larval stages. The present report concerns experiments on uptake and incorp- oration of C-Il lysine and C-14 leucine by embryos of the barn- acle, anus glandula (Darwin). Six distinct stages of develop- ment have been used in this study, ranging from early cleavage stages through the hatching nauplius. The results of this research indicate that there are one herk and possibly two peaks in the rate of incorporation of amino acids between cleavage of the first blastomere and hatching. As was had chee ef eune found with sea urchins, one of these is (around the mid-gastrula tage. This study also suggests that these embryos possess a transport system for concentration of amino acid. 1 Th 7e e 16. -2- MATERIALS AND METHODS taining and Handling the Eg 388 Adults of Balanus glandula were collected from rocks on China Point near the Hopkins Marine Station and transferred immediately a to the lab where they were maintained in a circulating water bath at 16° C. The embryos (found in sheet-like plates known as ovig- erous lamellae) were then taken from the barnacles, observed under a compound microscope to determine the stage of development, weighed, and immersed in millipore-filtered sea water at 16° C. All tests were made within two hours (of removing the barnacles ote vwee from the rocks and no longer than one hour after the ovigerous lam¬ ellae were taken from the mantle cavity. All incubations with the C-1l amino acids were performed at pH 7.7, which corresponds to the pH of the mantle cavity fluid. Classification of the Embryonic Stages The classification of the developmental stages is adapted from that described by Barnes (1965) for Balanus balanoides and Balanus balanus. The stages used herein have been characterized in the following manner. B. the formation and growth of the blastoderm over the yolk, C. the formation of the mesoblast and hypoblast (segmentation of the blastula), E. demarcation of the nauplius appendages (Barnes' stages D and E), F. the development of the appendages and the origin of the 16 -3- labrum and gut; further development of the appendages and the origin of the body cavity (Barnes' stages F and G), H. final stages of development; andincrease in transparency and the formation of the nauplius eye, and 1. the hatching nauplius (some nauplii still in the egg sack but in the process of hatching). Volume Determination Cirriped eggs are especially difficult to work with since dur- ing the earlier stages they are held tightly together in the ovig- erous lamellae and cannot be washed free of this tissue. Since fferent sets of eggs had to be compared on a volume basis in order to calculate the results of the experiments this proved to be a ss tupeete o complication. As a result, a method for determining the volume of the eggs was devised. Pieces of ovigerous lamellae were weighed and the number of eggs in the pieces counted. From this a curve was prepared establish¬ tanut mall Seaza ing a wet weight:number-of-eggs relationship (only an approximation since weight density changes during development, described by Barnes, 1965, were disregarded). The volume of a single egg was then cal¬ culated from the egg dimensions, assuming that the egg has the shape den dd gen sa a of an oblate spheroid of volume 1/3 Nabe (a=60,1 b-984). The volume of a single egg was calculated to be 1.16 X 10-° ml. With this a Eugd. wet weight: egg volume relationship was made. Preparation of the Ee A number of micro-organisms was sometimes found on the surface of the tissue binding the eggs together and on the eggs themselves. 16. 0 In order to be reasonably certain that these and any traces of bact¬ eria present would not affect the results of the experiments ad¬ versely the ovigerous lamellae were washed h-6 times with millipore- filtered sea water amd incubated in sea water containing .25 mg/ml streptomycin (Sigma Chemical Co.) and 150 units/ml penicillin (Sigma Chemical Co.). Isotope Incorporation In all of the experiments the pair of lamellae from one barnacle was separated and one lamella was incubated with C-11 lysine while the other was incubated with C-14 leucine. Three different con¬ centrations of amino acid was used:.1c/ml sea water, .33/c/ml 20 we u and 1.7c/ml.The duration of the incubations was twenty minutes. After incubation the samples were washed with 0.001 M C-12 mino acid and then 2ml of 5% trichloroacetic acid was added to the washed eggs in a Dounce homogenizer. The eggs were then homogen- ized and the TCA-homogenate centrifuged at 1130g for 15 minutes in a Servall RC-2B centrifuge. Part of the TCA-soluble supernatant was then collected, extracted twice with either, dried on a e planchet and (its activity counted in a Nuclear Chicago gas flow counter with mica window. wep The TCA-insoluble precipitate was resuspended in the TCA and mg of bovine serum albumin was added. This was then heated for twenty minutes at 90° C, filtered through 24 Schleicher & Schuell glass fiber filters and the residue then washed four times with 5% TCA-O.O5 M C-12 amino acid and twice with ether:ethanol:chloroform uhe (2:2:1). The filters were glued to planchets and counted as above. 16 0 -5. Isotopes The specific activities of the uniformly labeled C-11 amino acids (International Chemical and Nuclear Corporation) were: C-14 lysine, 200 mc/m; C-1h leucine, 198 mc/mM. LS rs detee For all developmental stages determinations were made of the amount of free isotope in the TCA-soluble phase and the amount of isotope incorporated into protein (TCA-insoluble phase). The degree of active uptake was estimated by comparing the total uptake into the eggs with the a mount of isotope originally present in an equal erca volume of external medium. As the different lamellae varied in size, the results are expressed in counts per minute/gram wet weight. This mode of ex- pression allows a comparison of thé different stages with other. 55 However, absolue comparison between stages is extremely difficult since a long developmental sequence has been here arbitrarily div¬ letaen ided into six phases. The actual time from fertilization to fully¬ formed nauplius is not known for B. glandula, but estima tes from other species suggest that the duration is at least twenty-four days. Thus, stages placed in the same category (e.g., Stage E) might actually be four to six days apart in time since fertilizat¬ ion. CA-soluble Phase In all experiments C-1 amino acid was found in the TCA-soluble fraction of the embryos, and the amount of labeled amino acid in this a med Hos neded Eg Eug od o er u de )stated 16. O -6 lerwen O Rag fraction differed yith the different developmental stages.There was usually variation between experiments but the radioactivity of the TCA-soluble fraction was generally the highest apt one of dee the three early stages (see figure 1). Figure 1 also shows dif¬ 10 ferences between leucine and lysine uptake in different experiments. This differenco is apparently real, and does not result from the difficulties in staging the embryos, since the lamellae used to compare leucine and lysine uptake were taken from the same animal. insoluble Phase TCA¬ Incorporation of labeled leucine and lysine was always lowest at stage B (blastoderm migration over the yolk) and generally in- creased to a peak at stages C-E (segmentation of the blastoderm to demarcation of the limb buds). The rate always decreased to Then uha slightly lower levels at the later stages. Total Incorporation The total amount of C-11 lysine and C-1 leucine found within the egg was always greater than the concentration of the C-1h amino acid external to the eggs. The ratio of these concentrations (inside/ outside) varied from.8 to 8.0, suggesting a type of active trans- port for these eggs. Although total uptake increased with increas- ing amounts of added C-14 amino acid, the ratio inside/outside decreased, suggesting a saturation of the "active transport" sys¬ tem. Table ! is a listing of the calculated numerical results of the experiment illustrated in figure 1-1. All of the data used to plot the graphs were compiled in this way for each experiment. Eug 16 -7- ESCUSSIO Much variation between different experiments was found which can probably be attributed to the aforementioned difficulties of classifying embryos with respect to age. Irrespective of these variations, it was found that the early stages always incorporated Aal less amino acid into protein than the later stages, and that Tyu peak incorporation occurred at stages C-E. Interpretation of the above data is complicated by an apparent bypassing of the endogenous amino acid pool by the added C-Il amino acids. The data show that at low external amino acid concentrations ——— (Fig. 1-111) greater than 503 of the amino acid taken into the cell (ct. Bres, 1063) was incorporated into protein. As Bala glandula probably con- tains a large amino acid "pool", the high percentage o of incorporation observed can be explained by a bypassing of the Adt en gut an ? "pool" by exogenous amino acid when transported across the cell Lee? merbrane into the cell, or by isotope discrimination. A similar type of compartmentation has been suggested to exist in the sea te Ge ax urchin embryo (Berg, 1965). This compartmentation, if it is this, is much larger in barnacle embryos, and may seriously hinder the interpretation of results obtained with C-11 amino acids. If this compartmentation is of similar magnitude throughout all stages, however, the general pattern found for incorporation is probably correct. The above results also indicated that barnacle embryos can utilize exogenous amino acids. It is interesting that two of the amino acids used, leucine and lysine, are also found in the fluid 167 C O -8- of the mantle cavity of B. glandula (Bergman, 1967). As the embryos are bathed in this fluid it is possible that these compounds are utilized by the embryos during their development. O ANOWE Special thanks are extended to Dr. David Epel for providing the inspiration, guidance and friendship which made this project a most enjoyable and instructive one. I am equally grateful for the assistance afforded me by all members of the staff of the Hopkins Marine Station. —p- BIDLTOGRAPHY Barnes, H., Studies in the biochemistry of Cirripede eggs, (1963), J. Mar. Biol. Ass., U.K., 15; 321-339 Berg, W., (1965), Exptl. Cell Res., 10; 169 Epel, D., Protein synthesis in sea urchin eggs: A "late" response to fertilization, (1967), Proc. Nat. Acad. Aci., 57, 899-906 Ferguson, J., Utilization of dissolved exogenous nutrients by the fishes, Asterias Forbesi and Henrica S. anguinolenta, (1967), The Biol. Bull. 132; 161-172 Gross, P.R., and G.H. Cousineau, Macromolecule synthesis and the niluence of actinomycin on early develöbment, Exptl. Cell Res., (1961), 368-395 33; Guidice, G.M., L. Vittorelli and A. Monroy, Investigationon the protein metabolism during the early development of the sea urchin eggs and embryos, (1958), Acta Embryol. Morph. Exper. 5; 113 Hultin, T., Incorporation of N-15 labeled glycine and alanine into the proteins of developing sea urchin eggs, (1951), Exptl. Cell Res., 191-196 3; Mitchison, J.M. and J.E. Cummins, The uptake of valine and cytidine by sea urchin embryos and its relation to the cell surface, (1966), J. Cell Sci., 1; .35-17 Stephens, G.C., and R. Schinske, Uptake of amino acids by marine invertebrates, (1961), Liminol. and oceanog., 6; 175-181 Uptake of organic material by aquatic invertebrates. II Accumulation of amino acids by the bamboo worm, Clymenella torquata, (1963), Biochom., Phisiol., 10;.191-209 Uptake of organic material by aquatic invertebrates. —2 lil Uptake of glycine byybrackish water annelids, (1964), Biol. Bull, 126; 150-162 170 O LEGED Figure 1: Three representative experiments with diffeeent con¬ centrations of C-11 mino acid. 1-I).lc/ml 1-II) .33c/ml — -11I) 1.7c/ml Table 1: A list of the calculated data for the experiment illust¬ rated in Fig. 1-I O 17 0 2. 2- 4. 2- C-la leucine 11 CE i 1 E H C14 lysine 1 CE B H ETCA-insoluble x10- TCA-soluble 10•9 II C E H III EH Fig. 17 O O TABLE 1 amno cpm cpm com wet y calculated weight volume external TCA-sol TCA-insol age acid leu 0.0092 2.8x10-3 1590 1760 11 lys 0.00h9 1.5x10-3 950 1980 leu lys 0.0085 2.6x10-3 1930 3210 619 leu 0.00hh 1.lx102 865 2680 277 lys 0.0061 1.9x10-3 1382 1920 Ml leu 0.0085 2.6x10 1760 1300 50 lys 0.0206 6.3x10-3 5100 3860 118 leu 0.0123 3.8210"2 2000 1320 757 lys 0.0122 3.7x10-3 2780 1580 120 leu 0.0233 7.1x10-3 3510 1120 110 lys 0.0196 6.0x10-3 1150 3680 391 — 7 in grams external exogenous cpm/equal volume of eggs 170 O APV SUPTIAR Emt ryos of Bala nus andula will concentrate amino acid from an external source and incorporate it into protein. Moreover the pattern of incorporation varies between different embryonic stages. It has been found that the lowest incorporation occur at the early stages and the highest during the middle stages of development. C 9804 N. E. 14th Street Bellevue, Washington July 18, 1967 Dear Dr. Epel, I am wondering if you have had time to read my paper again and pass any kind of judgement on it. I understand that you are probably pretty busy with your summer course so I don't mean to push you into anything. What I really want is an opinion. I have been asked by a medical school to which I am applying to write a short essay about any subject which I have studied and feel confident with. My studies last quarter would be ideal for this I think but I'm still not sure if you think my findings are valid enough. I suppose this is related to whether or not my paper is publishable. Any opinions of yours at this time would be appreciated. I certainly hope that the sun is shining a little brighter now than it did last qurter and that "Big Bertha" is functioning for Raffin! Sincerely, Ao 175