title: A novel role for Ascl1 in the regulation of mesendoderm formation via HDAC-dependent antagonism of VegT.
abstract: Maternally expressed proteins function in vertebrates to establish the major body axes of the embryo and to establish a pre-pattern that sets the stage for later-acting zygotic signals. This pre-patterning drives the propensity of Xenopus animal cap cells to adopt neural fates under various experimental conditions. Previous studies found that the maternally expressed transcription factor, encoded by the Xenopus achaete scute-like gene ascl1, is enriched at the animal pole. Asc1l is a bHLH protein involved in neural development, but its maternal function has not been studied. Here, we performed a series of gain- and loss-of-function experiments on maternal ascl1, and present three novel findings. First, Ascl1 is a repressor of mesendoderm induced by VegT, but not of Nodal-induced mesendoderm. Second, a previously uncharacterized N-terminal domain of Ascl1 interacts with HDAC1 to inhibit mesendoderm gene expression. This N-terminal domain is dispensable for its neurogenic function, indicating that Ascl1 acts by different mechanisms at different times. Ascl1-mediated repression of mesendoderm genes was dependent on HDAC activity and accompanied by histone deacetylation in the promoter regions of VegT targets. Finally, maternal Ascl1 is required for animal cap cells to retain their competence to adopt neural fates. These results establish maternal Asc1l as a key factor in establishing pre-patterning of the early embryo, acting in opposition to VegT and biasing the animal pole to adopt neural fates. The data presented here significantly extend our understanding of early embryonic pattern formation.
authors.affiliation: MOE Key Laboratory of Protein Sciences, Tsinghua University School of Life Sciences, Beijing 100084, China.
authors.forename: Li
authors.initials: L
authors.lastname: Gao
authors.affiliation: MOE Key Laboratory of Protein Sciences, Tsinghua University School of Life Sciences, Beijing 100084, China.
authors.forename: Xuechen
authors.initials: X
authors.lastname: Zhu
authors.affiliation: MOE Key Laboratory of Protein Sciences, Tsinghua University School of Life Sciences, Beijing 100084, China.
authors.forename: Geng
authors.initials: G
authors.lastname: Chen
authors.affiliation: CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Ma
authors.affiliation: MOE Key Laboratory of Protein Sciences, Tsinghua University School of Life Sciences, Beijing 100084, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: MOE Key Laboratory of Protein Sciences, Tsinghua University School of Life Sciences, Beijing 100084, China.
authors.forename: Aftab A
authors.initials: AA
authors.lastname: Khand
authors.affiliation: MOE Key Laboratory of Protein Sciences, Tsinghua University School of Life Sciences, Beijing 100084, China.
authors.forename: Huijuan
authors.initials: H
authors.lastname: Shi
authors.affiliation: MOE Key Laboratory of Protein Sciences, Tsinghua University School of Life Sciences, Beijing 100084, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Gu
authors.affiliation: MOE Key Laboratory of Protein Sciences, Tsinghua University School of Life Sciences, Beijing 100084, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Lin
authors.affiliation: Tianjin Normal University College of Life Science, Binshuixidao (extension line) 393, Xinqing District, Tianjin 300387, China.
authors.forename: Yuemeng
authors.initials: Y
authors.lastname: Chen
authors.affiliation: MOE Key Laboratory of Protein Sciences, Tsinghua University School of Life Sciences, Beijing 100084, China.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Zhang
authors.affiliation: MOE Key Laboratory of Protein Sciences, Tsinghua University School of Life Sciences, Beijing 100084, China.
authors.forename: Lei
authors.initials: L
authors.lastname: He
authors.affiliation: MOE Key Laboratory of Protein Sciences, Tsinghua University School of Life Sciences, Beijing 100084, China qhtaolab@tsinghua.edu.cn.
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Tao
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004475:Ectoderm / Q000187:drug effects / Q000196:embryology / Q000378:metabolism; D004625:Embryo, Nonmammalian / Q000187:drug effects / Q000378:metabolism; D004707:Endoderm / Q000187:drug effects / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D006655:Histone Deacetylases / Q000378:metabolism*; D008648:Mesoderm / Q000187:drug effects / Q000378:metabolism*; D060172:Morpholinos / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D055495:Neurogenesis / Q000187:drug effects / Q000235:genetics; D017434:Protein Structure, Tertiary; D020825:T-Box Domain Proteins / Q000378:metabolism*; D029867:Xenopus Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014982:Xenopus laevis / Q000196:embryology* / Q000235:genetics
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D006655:Histone Deacetylases; D060172:Morpholinos; D009419:Nerve Tissue Proteins; D020825:T-Box Domain Proteins; D029867:Xenopus Proteins; C103966:VegT protein, Xenopus; C080088:ascl1 protein, Xenopus
keywords: Ascl1; HDAC1; Mesendoderm; Transcriptional repressor; VegT; Xenopus