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Related Concept Videos

Determination01:51

Determination

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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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Pleiotropy01:33

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Pleiotropy is the phenomenon in which a single gene impacts multiple, seemingly unrelated phenotypic traits. For example, defects in the SOX10 gene cause Waardenburg Syndrome Type 4, or WS4, which can cause defects in pigmentation, hearing impairments, and an absence of intestinal contractions necessary for elimination. This diversity of phenotypes results from the expression pattern of SOX10 in early embryonic and fetal development. SOX10 is found in neural crest cells that form melanocytes,...
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Master Transcription Regulators

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Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a  complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
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Lineage Commitment01:21

Lineage Commitment

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Commitment is the  process whereby stem cells:
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Maintenance of the ES Cell State01:14

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The cells of the blastocyst inner cell mass only remain pluripotent for a short time. This state of pluripotency and self-renewal can be maintained in embryonic stem (ES) cell culture by adding specific chemicals or growth factors to ensure the cells can continue dividing and later differentiate into different cell types. In some cases, the cells are grown on a feeder layer of differentiated cells, which provides the growth factors and extracellular matrix components necessary for stem cell...
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Methods of Nuclear Reprogramming01:24

Methods of Nuclear Reprogramming

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Nuclear reprogramming is a process of transforming one cell type into an unrelated cell type by epigenetic changes that alter the cell’s original gene expression pattern. Such epigenetic changes force cells to express a different set of genes, which play a significant role in inducing transformation into other cell types. Nuclear reprogramming offers applications in reproductive cloning for livestock propagation and regenerative medicine — developing patient-specific cells for...
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  9. Predictive And Prognostic Markers
  11. Tbx6-dependent Sox2 Regulation Determines Neural Or Mesodermal Fate In Axial Stem Cells.
  1. Home
  3. Research Domains
  5. Biomedical And Clinical Sciences
  7. Oncology And Carcinogenesis
  9. Predictive And Prognostic Markers
  11. Tbx6-dependent Sox2 Regulation Determines Neural Or Mesodermal Fate In Axial Stem Cells.

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Tbx6-dependent Sox2 regulation determines neural or mesodermal fate in axial stem cells.

Tatsuya Takemoto1, Masanori Uchikawa, Megumi Yoshida

  • 1Graduate School of Frontier Biosciences, Osaka University, 1-3 Yamadaoka, Suita, Osaka 565-0871, Japan.

Nature
|February 19, 2011

View abstract on PubMed

Summary
This summary is machine-generated.

Tbx6 protein controls cell fate decisions in developing embryos. It represses Sox2 gene activity, ensuring that axial stem cells develop into paraxial mesoderm instead of neural tissue.

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Area of Science:

  • Developmental Biology
  • Stem Cell Biology
  • Molecular Genetics

Background:

  • Classical models proposed neural plate development originates solely from ectoderm.
  • Recent studies reveal common bipotential axial stem cells for neural plate and paraxial mesoderm.
  • Tbx6 null mutants exhibit ectopic neural tubes, suggesting a role in neural vs. mesodermal fate choice.

Purpose of the Study:

  • To elucidate the regulatory mechanism by which Tbx6 controls neural versus mesodermal fate choice.
  • To investigate the role of Tbx6 in regulating Sox2 expression during axial stem cell differentiation.

Main Methods:

  • Analysis of Tbx6 null mutant mouse embryos.
  • Cell-lineage tracing experiments.
  • Gene expression analysis of Sox2 and its enhancer N1.
  • CRISPR-mediated enhancer-N1 deletion in mutant embryos.
  • Misexpression of Sox2 transgene in wild-type embryos.

    • Main Results:

    • Tbx6 represses Sox2 via enhancer N1 activity in developing paraxial mesoderm.
    • In Tbx6 mutants, persistent enhancer N1 activity leads to ectopic Sox2 expression and neural tube formation.
    • Deletion of enhancer N1 in Tbx6 mutants rescues paraxial mesoderm development.
    • Tbx6-dependent repression of Wnt3a is implicated in this process.

    Conclusions:

    • Tbx6 is a key regulator determining the fate of axial stem cells.
    • Tbx6 promotes paraxial mesoderm specification by repressing Sox2 through enhancer N1.
    • This mechanism is crucial for preventing ectopic neural development from mesodermal precursors.