{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T23:21:11Z","timestamp":1776468071894,"version":"3.51.2"},"reference-count":63,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2005,6,6]],"date-time":"2005-06-06T00:00:00Z","timestamp":1118016000000},"content-version":"vor","delay-in-days":3901,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Teratology"],"published-print":{"date-parts":[[1994,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Staurosporine, an alkaloid isolated from <jats:italic>Streptomyces<\/jats:italic> species, is commonly used as a protein kinase C (PKC) inhibitor in animal investigations. In the present study, we used this compound to determine whether \u03b1<jats:sub>1<\/jats:sub>\u2010adrenergic stimulation\u2010induced situs inversus in rats is mediated by PKC. Embryos were explanted at 8 <jats:sc>A.<\/jats:sc> <jats:sc>M.<\/jats:sc> on day 9 of gestation. Those with a neural groove but with no visible neural folds (Stage 11a) were selected and were cultured in medium containing various concentrations of staurosporine with or without 50 \u03bcM of phenylephrine, an \u03b1<jats:sub>1<\/jats:sub>\u2010adrenergic agonist. At 10 <jats:sc>A.<\/jats:sc> <jats:sc>M.<\/jats:sc> On day 11 of gestation, embryos were examined for situs inversus and other abnormalities. Staurosporine, tested at 0.0001, 0.001, 0.01, 0.1, 0.375, and 0.5 \u03bcM (lethal concentration), did not block phenylephrine\u2010induced situs inversus at any concentration. However, staurosporine alone produced situs inversus at concentrations above 0.1 \u03bcM. At 0.5 and 1.0 \u03bcM, staurosporine also caused cyst\u2010like lesions projecting dorsally from the mesencephalon that we named \u201cmesencephalic vesicles\u201d and the formation of secondary somites. To confirm and further examine these unique effects of staurosporine both grossly and histologically, we conducted additional experiments using staurosporine from another source. Embryos were explanted between 6 <jats:sc>A.<\/jats:sc> <jats:sc>M.<\/jats:sc> and 9 <jats:sc>P.<\/jats:sc> <jats:sc>M.<\/jats:sc> on day 9 of gestation and were placed in one of the following groups according to their stage of development: 10b, 11a, 11b, 11c, 12\/sl\u20132, 12\/s3\u20134, and 12\/s5\u20136. Embryos were then cultured with various concentrations of staurosporine. Those cultured from Stage 11a exhibited similar lesions to those seen in the initial experiment but at somewhat higher concentrations of staurosporine. Embryos cultured from Stage 10b showed a similar pattern of lesions as seen at Stage 11a, except that higher concentrations of staurosporine were required to cause mesencephalic vesicles and secondary somites formation. Embryos cultured from Stage 11b showed similar effects to those cultured from younger stages except that maximum incidences of situs inversus were much lower. Those cultured from Stage 11c showed similar dose\u2013response to those cultured from Stage 11b except that the incidence of secondary somites formation was much higher. In addition, in approximately 40% (n = 25) of embryos treated with greater than 1. 0 \u03bcM of staurosporine, the growing end of the allantois did not reach the chorion and remained unattached in the exocoelomic cavity. Embryos cultured from Stage 12\/s1\u20132 showed similar effects to those cultured from Stage 11c except that incidences of failure of chorion\u2014allantois fusion were somewhat higher. Embryos cultured from Stages 12\/s3\u20134 and 12\/s5\u20136 were not viable after exposure to 1. 0 \u03bcM staurosporine. At 0. 5 \u03bcM, approximately 15% of embryos showed some kind of abnormality but no mesencephalic vesicles were observed. Histological examinations on the embryos cultured from Stage 11b with 1. 5 \u03bcM staurosporine revealed that the first sign of the mesencephalic vesicles was abnormal variable thickness and convolutions of the neuroepithelium lateral to the neural groove. These results suggest that situs inversus induced by stimulation of \u03b1<jats:sub>1<\/jats:sub>\u2010adrenergic receptors is not mediated through PKC. They also show that staurosporine causes situs inversus and various kinds of unique abnormalities in a dose\u2010dependent and stage\u2010specific manner. \u00a9 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/tera.1420500402","type":"journal-article","created":{"date-parts":[[2005,6,11]],"date-time":"2005-06-11T16:06:05Z","timestamp":1118505965000},"page":"261-274","source":"Crossref","is-referenced-by-count":10,"title":["Staurosporine does not prevent adrenergic\u2010induced situs inversus, but causes a unique syndrome of defects in rat embryos grown in culture"],"prefix":"10.1002","volume":"50","author":[{"given":"Masahiko","family":"Fujinaga","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hyoung W.","family":"Park","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas H.","family":"Shepard","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philip E.","family":"Mirkes","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey M.","family":"Baden","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2005,6,6]]},"reference":[{"key":"e_1_2_1_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/bja\/66.4.500"},{"key":"e_1_2_1_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/349084a0"},{"key":"e_1_2_1_4_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.79.18.5587"},{"key":"e_1_2_1_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/aja.1000440303"},{"key":"e_1_2_1_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(91)90288-A"},{"key":"e_1_2_1_7_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.111.4.1045"},{"key":"e_1_2_1_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(89)81494-2"},{"key":"e_1_2_1_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/bies.950141009"},{"key":"e_1_2_1_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/345078a0"},{"key":"e_1_2_1_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(91)90513-X"},{"key":"e_1_2_1_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/BFb0033873"},{"key":"e_1_2_1_13_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.118.3.731"},{"key":"e_1_2_1_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/0012-1606(92)90117-Y"},{"key":"e_1_2_1_15_1","first-page":"533","article-title":"Regulation of the epidermal growth factor receptor by growth\u2010modulating agents: Effects of staurosporine, a protein kinase inhibitor","volume":"50","author":"Friedman B.","year":"1990","journal-title":"Cancer Res."},{"key":"e_1_2_1_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/tera.1420430111"},{"key":"e_1_2_1_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/0012-1606(91)90067-D"},{"key":"e_1_2_1_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/tera.1420440411"},{"key":"e_1_2_1_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/tera.1420450611"},{"key":"e_1_2_1_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/tera.1420470610"},{"key":"e_1_2_1_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/tera.1420410202"},{"key":"e_1_2_1_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/tera.1420420510"},{"key":"e_1_2_1_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/tera.1420460211"},{"key":"e_1_2_1_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/0012-1606(92)90253-D"},{"key":"e_1_2_1_25_1","doi-asserted-by":"publisher","DOI":"10.1006\/dbio.1994.1109"},{"key":"e_1_2_1_26_1","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1242\/dev.118.1.163","article-title":"Occurrence of dorsal axis\u2010inducing activity around the vegetal pole of an uncleaved Xenopus egg and displacement to the equatorial region by cortical rotation","volume":"118","author":"Fujisue M.","year":"1993","journal-title":"Development"},{"key":"e_1_2_1_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-291X(88)80967-7"},{"key":"e_1_2_1_28_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.30.6.134"},{"key":"e_1_2_1_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/0960-9822(91)90111-9"},{"key":"e_1_2_1_30_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.116.2.347"},{"key":"e_1_2_1_31_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.bi.61.070192.003015"},{"key":"e_1_2_1_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/0955-0674(91)90110-K"},{"key":"e_1_2_1_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/359609a0"},{"key":"e_1_2_1_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-291X(90)91375-3"},{"key":"e_1_2_1_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/343617a0"},{"key":"e_1_2_1_36_1","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1093\/genetics\/76.4.795","article-title":"Hairpin\u2010tail: A case of post\u2010reduction gene action in the mouse egg?","volume":"76","author":"Johnson D. 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