FREEZE-FRACTURE STUDY OF THE DEVELOPING MORPHOLOGY OF HALIOTIS RUFESCENS OOCYTES TO NINE HOURS POST-FERTILIZATION By W. Howard Hess Hopkins Mar ine Station Pacific Grove, CA, 93950 ABSTRACT The technique of freeze-fracture in conjunction with scanning electron microscopy (FFSEM) was developed and succesfully used for viewing the developing morphology of the abalone embryo, Haliotis rufescens The nucleus and intracellular granules/vesicles could be visualized and changes in the distribution of granules followed during embryogenesis. The FFSEM procedure could be further developed as a research tool, and 1 present some possible improvements in the procedure. C INTRODUCTION The development of marine gastropods has been studied since the late 1800's, and excellent accounts have been published, e.g., on Crepidula (Conklin 1897), Trochus (Robert 1902), Patel/a (Patten 1886), and Haliotis (Crofts 1937). Yet, very little is known about the ultrastructure, aside from EM studies on processes of fertilization and maturation (Longo and Anderson 1969, 1970). Here report on the Haliotis embryo, using a novel procedure, FFSEM. report on both surface views but especially internal structures. The most interesting aspect of FFSEM is the ability to view intracellular granules/vesicles, most probably yolk granules, and their change in distribution during their development. MATERIALS AND METHODS Aquisition and Cuturing of Embryos The reported studies were all done with one batch of oocytes and embryos, obtained from the Granite Canyon Laboratory of the California Department of Fish and Game (Carmel, CA). The embryos were maintained at 15 C° within a 1000 ml beaker containing microfiltered sea water (MSW) and were suspended 1.5 cm off the beaker bottom via nylon mesh (Nytex, 120 u) at a concentration below 5/ml, and aerated with an air-stone. Light Microscopy Whole oocytes and embryos were viewed at 0.0 and 30 min post-fertilization (PF), and then viewed and photographed at 2, 3, 4.5, 6.5, and 9 h PF with a phase-contrast microsope using dark-field or bright-field settings. Photographs were made on 100 ASA color slide film with a fully-automatic 35 mm camera conected via a T-mount to the light microscope. Freeze-Fracture Preparation for Scanning Flectron Microscopy Oocytes and cultured embryos were concentrated with nylon mesh (Nytex, 120 u) and samples (0.1-0.25 ml) were pipeted into 25m1 beakers for fixation at 0.0, 10, 20, and 30 min PF, and then at 1, 2, 3, 4.5, and 6.5 h PF. Specimens were fixed in 22 glutaraldahyde in 802 MSW containing 1.22 HEPES (pH 7.3) for a minimum of 2 hrs at 4° (at min ratio Iml Sample : 50ml Fix), washed twice for 5 min in distilled water (DW), and post-fixed for 5-1 hr at 23 C° at a 1:1 ratio in 12 osmium tetroxide prepared in MSW, and rewashed twice for 5 min in DW. Fixed samples were then mixed (1:1) with a warm suspension of 3% agar, pipeted onto paraf ilm sheets, air cooled for 1-2 min, dehydrated by immersion for at least 10 minutes each in 20, 30, 40, 50, 60, 70, 80, 90, and 100% ethanol, frozen by immersion in liquid nitrogen (1-2 min), fractured with a chilled razor and then reimmersed in 100% ethanol. Fractured samples were then either critical-point dried or immersed in hexamethyldisilazane for final drying, "glued" onto metal stubs via colloidial graphite with the fractured suface facing upwards, and sputter-coated with gold. Coated samples were then viewed under the SEM or stored in a dessicator until viewing. RESULTS Development of Embryos In the batch of embryos used, 95% of the embryos developed normally during the first nine hours, 3% did not undergo cleavage, and 28 developed abnormally (fig. 1). At twenty-four hrs PF 67% of the embryos showed normal but slow growth, 30% of the embryos appeared abnormal, and 3% had not undergone cleavage. C Light Microscope Observations For purposes of interpreting the images obtained by FFSEM, it is necessary to describe development as seen under the light microscope. Examination of Haliotis oocytes and embryos via the light microscope provided a general view of its development which seems to follow that of the Crepidula as described by E. G. Conklin in 1897 (see Appendix I for dev. of Crepidula). The 150 u oocytes were loosely surrounded by a translucent chorion and exhibited no polarity/asymmetry in shape or color (fig. 1). When viewed macroscopically, the eggs were green; however, under the microscope the eggs were green-brown and there was no appearent pigment localization (as opposed to later). By 2 hrs PF, the embryos had developed into two seemingly identical cells, equivalent in size and color (fig. 2. For comparision to 2-cell Crepidula see Appendix! fig. 5). By 3 hrs PF, the embryos were in a four cell stage with blastomeres similar in size and color (fig. 3. For comparision to 4-cell Crepidula see AppendixI fig. 11). By 4.5 hrs PF, the embryos were at the eight-cell stage and asymmetry was now apparant in blastomere size and yolk distribution. These embryos consisted of a micromere quartet of four translucent, green cells resting on a macromere quartet of four larger opaque, brown cells (figs. 4-5. For comparision to 8-cell Crepidula see Appendix 1 fig. 13). By 6.5 hrs PF, the embryos were in the 25-cell stage consisting of twenty-one micromeres and four macromeres. The mass of the micromere region had increased and the mass of the macromere region had corespondingly decreased (fig. 6. For comparision to 25-cell Crepidula see Appendix I fig. 24). By 9 hrs PF, the embryos were approximately sixty cells, of which four were macromeres, and approximately 56 were micromeres. The micromeres were in the process of enveloping the macromeres (No photographed image. For 60-cell Crepidula see Appendix 1 fig. 36) SEM Extracellular lmages Extracellular items of interest included the chorion, the cell surface, polar bodies and sperm. The chorion was seen at all stages of development; its general charcteristics did not differ from stage to stage but its relation to the oocyte or embryo varied significantly because of differences in the fracture plane (compare figs. 7, 8, &11). In contrast, veiws of the cell surface differed according to developmental stage (compare figs. 7,1 1,14, &15 ). The cell surfaces of oocytes, but not embryos, were wrinkled (perhaps the oocytes are more suceptible to osmotic changes than are the embryos) (fig. 7). By comparison, the cell surfaces of the embryos were relatively smooth, but at high magnification (x 2.5 K) they showed irregularities which may have been caused by the underlying yolk granules (fig. 12). The polar bodies, seen only on 2-cell and 8-cell specimens, were located at the animal pole of these embryos (figs. 11,12, &14). The sperm cells, also seen primarily on 2-cell and 8-cell specimens, were found on the chorion and on the cell's exterior (figs. 11,12, &14). Intracellular lmages The intracellular structures visualized were granules/vesicles and nuclei. Most of the fractured vesicles were empty, but some contained what appeared to be fractured or intact yolk granules (figs. 7-10, 13, 16, 17). The granule distribution in oocytes to 2-cell-stage was in mosrt cases uniform (figs. 7-10, 13 but in a few cases some localization was seen (figs. 7-10, 13. A polar distribution of granules could be seen by the eight-cell stage (4.5 hrs PF) as shown in fig. 13 lcompare with sectioned Crepidula (4-cell and 12-cell). Appendix I figs. 83 & 841. Further asymmetry in the distribution of the granules/vesicles could be seen in the 6.5 hr samples (figs. 16, & 17). Also, micromeres with associated nuclei could be seen surrounding the granule/vesicle filled cells, macromeres as shown in figs. 15 & 16 Icompare with sectioned Crepidula (29-cell), Appendix fig. 851. DISCUSSION The FFSEM images of this study are most interesting when compared with Conklin's images of the developing Crepidula and with the light microscope images. One set of structures seen in both the FFSEM images and Conklin's images is polar bodies. These structures were first found on the Haliotis at the 2-cell stage (figs. 11 & 12), but are shown to emerge in the Crepidula prior to first cleavage (Appendix 1 fig. 2). Also, a comparison should be made between the nuclei seen in the FFSEM images and Conklin's sectioned images. In both cases, the nuclei could only be seen in micromere cells (figs. 16 &17 and Appendix I figs. 84 & 85) (either the cells containing the granules had no nucleus, or the granules were shielding the nuclei from view). The most interesting comparison involves the FFSEM images, LM images, and Conklin's images. First, the distribution of granules/vesicles in the FFSEM images seems to correspond to the distribution of pigment in the light microscope images (seen most easily by comparing fig. 13 to fig. 4). Second, these pigment and granule/vesicle distributions seem to correspond to the patterns of yolk distribution shown in Conklin's images of the Crepidula (this relation can be visualized most easily be comparing figs. 16 & 17 to Appendix I fig. 85). Therefore, it is likely that the granules/vesicles seen in the FFSEM images and the brown pigment seen in the LM images are yolk granules which are being distributed in the developing Haliotis embryos in a manner similar to that of the Crepidula. The technique of FFSEM used in this investigation is a relatively simple, but highly effective, method for visualization of intracellular structures: FFSEM provided a unique three-dimensional view of the internal as well as external aspects of the embryo. With a few modifications, FFSEM could become particularly useful for viewing intracellular vesicles. Such improvements might include, but not AKNOWLEDGMENTS wish to thank the California Department of Fish and Game and the members of the Granite Canyon Laboratory (especially Michael Harris) for Haliotis specimens and use of their facilities, Greg Baxter for his assistance and advice, Chris Patton for his technical support on SEM, and Dr. David Epel for his assistance, advice and use the of his facilities. LITERATURE CITED Conklin, E. G. (1897) J. Morph., 13, 1-226. Crofts, D. R. (1937) Philos. Trans. Roy. Soc. Lond., 228B, 219-268. Longo, F. J. and Anderson, E. (1969a) Cytological aspects of fertilization in the lamellibranch, Mytilitus edulis 1. Polar body formation and development of the female pronucleus. J. Esp. 200l, 172, 69-96 Longo, F. J. and Anderson, E. (1970a) An ultrastructural analysis of fertilization in the surf clam, Spisula solidissimal. Polar body formation and development of the female pronucleus. J Ultrastruct. Res, 33, 495-514. Longo, F. J. and Anderson, E. (1970b) An ultrastructural analysis of fertilization in the surf clam, Spisula solidissimall. Development of the male pronucleus and the association of the maternally and paternally derived chromosomes. J. Ultrastruct. Res, 33, 515-527. Patten W. (1886) Arb. zool. Inst. Univ. Wien., 6, 149-174 Robert A. (1902) Arch. Zool. exp. gén. (3), 10, 270-538 FIGURE LEGEND Fig. 1. Dark-field image (6.5 h stage) showing an abnormal embryo (upper-left), and an unfertilized oocyte (lower-right). Fig. 2. Dark-field image (2 h stage) showing 2-cell embryos with sperm attatched to chorion. Fig. 3. Bright-field image (3 h stage) showing a 4-cell embryo Fig. 4. Dark-field image (4.5 h stage) showing 8-cell embryos with sperm attatched to chorion and asymmetrical distribution of pigments: green is present mostly in the micromeres and brown is present mostly in the macromeres. Fig. 5. Same as fig. 4. Fig. 6. Dark-field image (6.5 h stage) showing 25-cell embryos with sperm attatched to chorion and asymmetrical distribution of pigments Fig. 7. FFSEM image of an oocyte showing the cell surface and internal structures (vesicles,fractured granules and intact granules). (x660) Fig. 8. FFSEM image of oocytes showing variations in the fractue plane, the chorion, the cell surface and internal structures (vesicles, fractured granules and intact granules). (x200) Fig. 9. FFSEM image (20 min stage) showing the internal structure of a L-cell embryo (vesicles, fractured granules and intact granules). (x1000) Fig. 10. FFSEM image (1 h stage) showing the cell surface, chorion, and internal structure of a Lcell embryo (vesicles, fractured granules and intact granules are asymmetrically distributed). 13 (x880) Fig. 11. FFSEM image (2 h stage) of 2-cell embryos showing the cell surface, chorion, sperm, polar bodies, and granules. (x360) Fig. 12. FFSEM image (2 h stage) of a 2-cell embryo showing the cell surface, chorion, sperm, and a polar body. (x2.5 k) Fig. 13. FFSEM image (4.5 h stage) showing the intertnal characteristics of an 8-cell embryo: asymmetrical distribution of granules and vesicles (most of the granules and vesicles are present in the macromeres, while few are present at the perimeter of the micromeres). (x650) Fig. 14. FFSEM image (4.5 h stage) showing the extertnal characteristics of an 8-cell embryo: two polar bodies resting in the cleavage furrow of the micromere quartet which, in turn, is resting on the macromere quartet. In addition, a bit of chorion and some sperm can be seen on the cell surface. (x650) Fig. 15. FFSEM image (6.5 h stage) showing the extertnal characteristics of a fractured 25-cell embryo: the cell surface and the cleavage pattern of the micromeres (foreground) as well as macromeres (background) can be seen. (x650) Fig. 16. FFSEM image (6.5 h stage) showing the intertnal and external characteristics of a 25-cell embryo: asymmetrical distribution of granules and vesicles is a key feature of the internal morphology. Note that nuclei can be seen in some of the granule-free micromeres. On the exterior, the cell surface and the chorion can be seen. (x650) Fig. 17. FFSEM image (6.5 h stage) showing the intertnal characteristics of a 25-cell embryo: asymmetrical distribution of granules and vesicles is a key feature of the internal morphology Note that nuclei can be clearly be seen in some of the granule-free micromeres. (x810) Fig. 2. Fig. 4. Fig. 3. Fig. 6. Fig. 5. ig. 11 Fig. 12. Fig. 14. 19 83. oga 808 8o oog alo FIG. 84. Section of egg Eight cells. so 8888 Sog Logggdegs FIG. 83. Section of egg Four cells. 84. 8 o 9 G B 888888 FIG. 85. Section of egg Sixty cells. 24 necessarily be limited to reduced lipid extraction, reduced osmotic changes, elimination of "ice" crystal formation, and most importantly improved membrane resolution. Lipid extraction might be reduced simply by the shortening of the duration of glutaraldehyde fixation, but if this proves ineffective or other-wise undesireable, then simultaneous fixation by gluteraldehyde and osmium tetroxide mixtures might be used. In addition, intracellular membranes might be better resolved by metallic impregnation of the the phospholipids from which they are comprised. Then, to prevent osmotic disruption, sucrose (or other compounds) might be added (probably prior to osmium tetroxide fixation), or changes in drying media might be tried. Also, "ice" crystal formation, if occuring, might be remedied by a change in the drying medium, or by the addition of an "antifreeze" to the medium. Finally, selective alignment of embryos (if possible) and or serial-fracture of embryos might produce images which are more easily interpretable than those obtained by the present method of FFSEM. 10 Fig. 8. Fig. 9. Fig. 10. Fig. 16. ig. 17 21 22 APPENDIX Fiqures from E. G. Conklin's The Embryology of the Crepidula. FIG. 5. Completion of first cleavage furrow. FIG. 11. Four cells. 1 P.. FIG. 13. Eight cells. Pr 23. jaii. 3a ja ta La'. 2a sa id ed' MEsed) FIG. 23. Twenty-nine cells. 25“ 36. Ja Lale Lee 34 3d“ Jeu Jc FIG. 36. Sixty cells. 1b“ 15" e1 G 1 1c 1c 2b“.. 10 gu c 23 94. d a 1c“ la ME(4d) àd' FIG. 24. Side view of egg of about the same stage as Fig. 23.