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Wnt is a zygotic effect gene that is expressed during very early embryonic development. It regulates various processes in animals starting from early development through the adult stage, such as organogenesis in the embryo and maintenance of neuronal and blood stem cells. Wnt proteins can induce a wide variety of intracellular pathways depending upon the specific abilities of different Wnt ligands to form a complex with shared and cognate receptors in the presence of different co-receptors. The...
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The gene encoding the main signaling molecules of the Wnt signaling pathways (the Wnt proteins) was discovered almost four decades ago by Nüsslein-Volhard and Wieschaus. They identified and originally named the gene "wingless" (wg) after a phenotype discovered during their landmark genetic screen in Drosophila for body pattern defects. At around the same time, another researcher named Harold Varmus found that a murine tumor virus activates the mammalian wg homolog, Int-1, which...
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During embryogenesis, cells become progressively committed to different fates through a two-step process: specification followed by determination. Specification is demonstrated by removing a segment of an early embryo, “neutrally” culturing the tissue in vitro—for example, in a petri dish with simple medium—and then observing the derivatives. If the cultured region gives rise to cell types that it would normally generate in the embryo, this means that it is specified. In...
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A TALE/HOX code unlocks WNT signalling response towards paraxial mesoderm.

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Cells use a BRACHYURY-TALE/HOX code to control gene expression during development. This mechanism ensures proper lineage specification by regulating chromatin accessibility and WNT signaling in neuromesodermal progenitors.

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Area of Science:

  • Developmental Biology
  • Epigenetics
  • Molecular Biology

Background:

  • Cellular context dictates responses to signaling cues, crucial for lineage specification.
  • Neuromesodermal progenitors (NMPs) utilize WNT signaling for expansion and differentiation.
  • Temporal control of WNT-activated gene expression in NMPs remains poorly understood.

Purpose of the Study:

  • To elucidate the mechanism by which WNT signaling temporally activates lineage-specific genes in NMPs.
  • To identify the key factors and chromatin modifications involved in paraxial mesoderm induction.
  • To understand how WNT signaling drives NMPs towards a specific developmental fate.

Main Methods:

  • Investigated the role of TALE/HOX transcription factors in NMP differentiation.
  • Analyzed chromatin accessibility at WNT-responsive regulatory regions.
  • Examined the recruitment of WNT pathway components, including LEF1, to target genes.

Main Results:

  • Paraxial mesoderm induction depends on TALE/HOX combinatorial activity.
  • A BRACHYURY-TALE/HOX code was identified that represses NMP genes and activates differentiation.
  • This code destabilizes nucleosomes, creating a permissive chromatin landscape for LEF1 recruitment.
  • This process unlocks the WNT transcriptional program driving NMPs to the paraxial mesodermal fate.

Conclusions:

  • The BRACHYURY-TALE/HOX code is essential for temporal WNT signal interpretation and lineage specification.
  • Chromatin remodeling by this code facilitates precise WNT-mediated transcriptional activation.
  • This mechanism ensures NMPs commit to the paraxial mesoderm lineage.