Return to search results Title: A novel role for ASCL1 in the regulation of mesendoderm formation via HDAC-dependent antagonism of VegT function

Summary

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-pattern 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. In this study, we have 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. Secondly, 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 has 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 the pre-pattern 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.

Contributors: Li Gao, Xin Ma, Qinghua Tao

Experiment Type: Examination of genes expression in control (cMO) and Ascl1 MO knockdown (AMOs) embryos by deep sequencing.

Experiment Reagents: ascl1 mismatch cMO1, ascl1 mismatch cMO2, ascl1 MO3, [-][+]


Article: XB-ART-51664, PubMed

Source: NCBI GEO, Xenbase Download

Sample	View		GSMs	Assay Type
WE + Ascl1 control MO - NF11 GSM2040681  GSM2040682  GSM2040683  RNA-Seq Xla   [-] [+] Background: Xla.Outbred Manipulations: Manipulation Type Reagent Target Gene Stage Treatment Area morpholino injection ascl1 mismatch cMO1 NF stage 1 zygote morpholino injection ascl1 mismatch cMO2 NF stage 1 zygote Conditions: Tissue Assay Stages ChIP Antibody embryo NF stage 11      WE + Ascl1 MO - NF11 DEG GSM2040684  GSM2040685  GSM2040686  RNA-Seq Xla   [-] [+] Background: Xla.Outbred Manipulations: Manipulation Type Reagent Target Gene Stage Treatment Area morpholino injection ascl1 MO3 ascl1 NF stage 1 zygote morpholino injection ascl1 MO4 ascl1 NF stage 1 zygote Conditions: Tissue Assay Stages ChIP Antibody embryo NF stage 11

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