{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T18:12:16Z","timestamp":1775239936145,"version":"3.50.1"},"reference-count":42,"publisher":"The Company of Biologists","issue":"19","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2008,10,1]]},"abstract":"<jats:p>In mouse, the establishment of left-right (LR) asymmetry requires intracellular calcium (Cai2+) enrichment on the left of the node. The use of Cai2+ asymmetry by other vertebrates, and its origins and relationship to other laterality effectors are largely unknown. Additionally, the architecture of Hensen's node raises doubts as to whether Cai2+ asymmetry is a broadly conserved mechanism to achieve laterality. We report here that the avian embryo uses a left-side enriched Cai2+ asymmetry across Hensen's node to govern its lateral identity. Elevated Cai2+ was first detected along the anterior node at early HH4, and its emergence and left-side enrichment by HH5 required both ryanodine receptor (RyR) activity and extracellular calcium, implicating calcium-induced calcium release (CICR) as the novel source of the Cai2+. Targeted manipulation of node Cai2+ randomized heart laterality and affected nodal expression. Bifurcation of the Cai2+field by the emerging prechordal plate may permit the independent regulation of LR Cai2+ levels. To the left of the node, RyR\/CICR and H+V-ATPase activity sustained elevated Cai2+. On the right, Cai2+ levels were actively repressed through the activities of H+K+ATPase and serotonin-dependent signaling, thus identifying a novel mechanism for the known effects of serotonin on laterality. Vitamin A-deficient quail have a high incidence of situs inversus hearts and had a reversed calcium asymmetry. Thus, Cai2+ asymmetry across the node represents a more broadly conserved mechanism for laterality among amniotes than had been previously believed.<\/jats:p>","DOI":"10.1242\/dev.018861","type":"journal-article","created":{"date-parts":[[2008,8,29]],"date-time":"2008-08-29T00:45:44Z","timestamp":1219970744000},"page":"3271-3280","source":"Crossref","is-referenced-by-count":21,"title":["A ryanodine receptor-dependent Cai2+ asymmetry at Hensen's node mediates avian lateral identity"],"prefix":"10.1242","volume":"135","author":[{"given":"Ana","family":"Garic-Stankovic","sequence":"first","affiliation":[{"name":"Department of Nutritional Sciences, University of Wisconsin-Madison, Madison,WI 53706, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcos","family":"Hernandez","sequence":"additional","affiliation":[{"name":"Department of Nutritional Sciences, University of Wisconsin-Madison, Madison,WI 53706, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"George R.","family":"Flentke","sequence":"additional","affiliation":[{"name":"Department of Nutritional Sciences, University of Wisconsin-Madison, Madison,WI 53706, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maija H.","family":"Zile","sequence":"additional","affiliation":[{"name":"Department of Food Science and Human Nutrition, Michigan State University,East Lansing, MI 48824, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susan M.","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Nutritional Sciences, University of Wisconsin-Madison, Madison,WI 53706, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"237","reference":[{"key":"2021042605492793300_REF1","doi-asserted-by":"crossref","unstructured":"Adams, D. 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