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In zebrafish, although proper differentiation of all <jats:styled-content style=\"fixed-case\">AH<\/jats:styled-content> cell types has been shown to require Notch signaling within a period of 14\u201316\u00a0h postfertilization (hpf), the mechanisms underlying this process remain to be elucidated. Herein, we observed using the Notch inhibitor dibenzazepine (<jats:styled-content style=\"fixed-case\">DBZ<\/jats:styled-content>) that Notch signaling also contributed to <jats:styled-content style=\"fixed-case\">AH<\/jats:styled-content> cell specification beyond 16 hpf. Specification of distinct cell types was perturbed by <jats:styled-content style=\"fixed-case\">DBZ<\/jats:styled-content> treatment for different time frames, suggesting that <jats:styled-content style=\"fixed-case\">AH<\/jats:styled-content> cells are specified by Notch\u2010dependent and cell\u2010type\u2010specific mechanisms. We also found that two <jats:italic>hes<\/jats:italic>\u2010family genes, <jats:italic>her4.1<\/jats:italic> and <jats:italic>hey1<\/jats:italic>, were expressed in the developing <jats:styled-content style=\"fixed-case\">AH<\/jats:styled-content> under the influence of Notch signaling. <jats:italic>her4.1<\/jats:italic> knockdown reduced expression of <jats:italic>proopiomelanocortin a<\/jats:italic> (<jats:italic>pomca<\/jats:italic>), <jats:italic>growth hormone<\/jats:italic> (<jats:italic>gh<\/jats:italic>), and <jats:italic>prolactin<\/jats:italic>, whereas <jats:italic>hey1<\/jats:italic> was responsible only for <jats:italic>gh<\/jats:italic> expression. Simultaneous loss of both Her4.1 and Hey1 produced milder phenotypes than that of <jats:styled-content style=\"fixed-case\">DBZ<\/jats:styled-content>\u2010treated embryos. Moreover, <jats:styled-content style=\"fixed-case\">DBZ<\/jats:styled-content> treatment from 18 hpf led to a significant down\u2010regulation of both <jats:italic>gh<\/jats:italic> and <jats:italic>pomca<\/jats:italic> genes only when combined with injection of a subthreshold level of <jats:italic>her4.1<\/jats:italic>\u2010morpholino. These observations suggest that multiple downstream effectors, including Her4.1 and Hey1, mediate Notch signaling during <jats:styled-content style=\"fixed-case\">AH<\/jats:styled-content> cell specification.<\/jats:p>","DOI":"10.1111\/gtc.12358","type":"journal-article","created":{"date-parts":[[2016,3,31]],"date-time":"2016-03-31T19:59:55Z","timestamp":1459454395000},"page":"492-504","source":"Crossref","is-referenced-by-count":5,"title":["Temporal effects of Notch signaling and potential cooperation with multiple downstream effectors on adenohypophysis cell specification in zebrafish"],"prefix":"10.1111","volume":"21","author":[{"given":"Yoshinari","family":"Nakahara","sequence":"first","affiliation":[{"name":"Department of Biological Science Graduate School of Science Hiroshima University Higashi\u2010Hiroshima Hiroshima 739\u20108526 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