title: SoxB1 downregulation in vegetal lineages of sea urchin embryos is achieved by both transcriptional repression and selective protein turnover.
abstract: Patterning of cell fates along the sea urchin animal-vegetal embryonic axis requires the opposing functions of nuclear beta-catenin/TCF-Lef, which activates the endomesoderm gene regulatory network, and SoxB1, which antagonizes beta-catenin and limits its range of function. A crucial aspect of this interaction is the temporally controlled downregulation of SoxB1, first in micromeres and then in macromere progeny. We show that SoxB1 is regulated at the level of protein turnover in these lineages. This mechanism is dependent on nuclear beta-catenin function. It can be activated by Pmar1, but not by Krl, both of which function downstream of beta-catenin/TCF-Lef. At least partially distinct, lineage-specific mechanisms operate, as turnover in the macromeres depends on entry of SoxB1 into nuclei, and on redundant destruction signals, neither of which is required in micromeres. Neither of these turnover mechanisms operates in mesomere progeny, which give rise to ectoderm. However, in mesomeres, SoxB1 appears to be subject to negative autoregulation that helps to maintain tight regulation of SoxB1 mRNA levels in presumptive ectoderm. Between the seventh and tenth cleavage stages, beta-catenin not only promotes degradation of SoxB1, but also suppresses accumulation of its message in macromere-derived blastomeres. Collectively, these different mechanisms work to regulate precisely the levels of SoxB1 in the progeny of different tiers of blastomeres arrayed along the animal-vegetal axis.
authors.affiliation: Department of Biology, University of Rochester, Rochester, NY 14627, USA. langerer@mail.nih.gov
authors.forename: Lynne M
authors.initials: LM
authors.lastname: Angerer
authors.forename: Laurel A
authors.initials: LA
authors.lastname: Newman
authors.forename: Robert C
authors.initials: RC
authors.lastname: Angerer
mesh_terms: D000818:Animals; D019070:Cell Lineage; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism; D015536:Down-Regulation; D004475:Ectoderm / Q000378:metabolism; D004625:Embryo, Nonmammalian / Q000378:metabolism*; D005786:Gene Expression Regulation; D018507:Gene Expression Regulation, Developmental; D049452:Green Fluorescent Proteins / Q000378:metabolism; D017403:In Situ Hybridization; D008648:Mesoderm / Q000378:metabolism; D018613:Microscopy, Confocal; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000378:metabolism; D055748:SOXB1 Transcription Factors; D012617:Sea Urchins; D015398:Signal Transduction; D013997:Time Factors; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000096:biosynthesis*; D014158:Transcription, Genetic; D051176:beta Catenin
chemical_list: D003598:Cytoskeletal Proteins; D012333:RNA, Messenger; D055748:SOXB1 Transcription Factors; C402390:SoxB1 protein, Strongylocentrotus purpuratus; D015534:Trans-Activators; D014157:Transcription Factors; D051176:beta Catenin; D049452:Green Fluorescent Proteins