title: C. elegans pur alpha, an activator of end-1, synergizes with the Wnt pathway to specify endoderm.
abstract: The endoderm of C. elegans arises entirely from a single progenitor cell, the E blastomere, whose identity is specified by GATA type transcription factors, including END-1. In response to an inductive interaction mediated through Wnt/MAP kinase signaling pathways, POP-1, a Lef/Tcf-type transcription factor, restricts end-1 transcription to the posterior daughter of the mesendoderm progenitor (EMS cell), resulting in activation of endoderm differentiation by the SKN-1 and MED-1/2 transcription factors. We purified a factor from semi-synchronized early embryos that binds to an end-1 cis regulatory region critical for its endoderm-specific expression. Mass spectrometry identified this protein, PLP-1, as a C. elegans orthologue of the vertebrate pur alpha transcription factor. Expression of end-1 is attenuated in embryos depleted for PLP-1. While removal of plp-1 activity alone does not prevent endoderm development, it strongly enhances the loss of endoderm in mutants defective for the Wnt pathway. In contrast, loss of PLP-1 function does not synergize with mutants in the endoderm-inducing MAPK pathway. Moreover, nuclear localization of PLP-1 during interphase requires components of the MAPK pathway, suggesting that PLP-1 is influenced by MAPK signaling. PLP-1 is transiently asymmetrically distributed during cell divisions, with higher levels in the chromatin of the future posterior daughter of EMS and other dividing cells shortly after mitosis compared to that in their sisters. These findings imply that PLP-1 acts as a transcriptional activator of end-1 expression that may be modulated by MAPK signaling to promote endoderm development.
authors.affiliation: Department of Molecular, Cellular and Developmental Biology, University of California, Santa Barbara, CA 93106, USA.
authors.forename: Eric S
authors.initials: ES
authors.lastname: Witze
authors.forename: Erin D
authors.initials: ED
authors.lastname: Field
authors.forename: Donald F
authors.initials: DF
authors.lastname: Hunt
authors.forename: Joel H
authors.initials: JH
authors.lastname: Rothman
mesh_terms: D000818:Animals; D029742:Caenorhabditis elegans Proteins; D002477:Cells / Q000166:cytology; D004627:Embryonic Induction; D004707:Endoderm / Q000166:cytology* / Q000254:growth & development; D050980:GATA Transcription Factors; D005786:Gene Expression Regulation; D020935:MAP Kinase Signaling System; D014157:Transcription Factors; D051153:Wnt Proteins / Q000378:metabolism*
chemical_list: D029742:Caenorhabditis elegans Proteins; C109211:END-1 protein, C elegans; D050980:GATA Transcription Factors; D014157:Transcription Factors; D051153:Wnt Proteins