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Development 2016 Feb 01;1433:492-503. doi: 10.1242/dev.126292.
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A novel role for Ascl1 in the regulation of mesendoderm formation via HDAC-dependent antagonism of VegT.

Gao L , Zhu X , Chen G , Ma X , Zhang Y , Khand AA , Shi H , Gu F , Lin H , Chen Y , Zhang H , He L , Tao Q .

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.

PubMed ID: 26700681
PMC ID: PMC4760308
Article link: Development

Species referenced: Xenopus laevis
Genes referenced: ascl1 bix1.3 eomes fgf8 h3-3a hdac1 hdac2 hdac3 mixer myc nodal nodal1 nog odc1 polr2a pou5f3 pou5f3.2 pou5f3.3 sox17a sox2 tbxt tubb2b vegt wnt11b
Antibodies: Acetylated H3f3 Ab37 Mapk1 Ab1 Mapk1 Ab10 Methyl-h3f3a Ab38 Myc Ab5 Smad1 Ab13 Smad1 Ab7 Smad2 Ab4 Smad2 Ab8 h3f3a Ab32 phospho-Polr2 Ab9
Morpholinos: ascl1 MO3 ascl1 MO4 ascl1 MO6 ascl1 MO7 hdac1 MO1 hdac1 MO3 hdac2 MO1 vegt MO4

GEO Series: GSE76915: Xenbase,  NCBI

Article Images: [+] show captions
References [+] :
Ali, The phosphorylation status of Ascl1 is a key determinant of neuronal differentiation and maturation in vivo and in vitro. 2014, Pubmed, Xenbase