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Related Concept Videos

Gastrulation01:56

Gastrulation

Gastrulation establishes the three primary tissues of an embryo: the ectoderm, mesoderm, and endoderm. This developmental process relies on a series of intricate cellular movements, which in humans transforms a flat, “bilaminar disc” composed of two cell sheets into a three-tiered structure. In the resulting embryo, the endoderm serves as the bottom layer, and stacked directly above it is the intermediate mesoderm, and then the uppermost ectoderm. Respectively, these tissue strata will form...

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An Explant Assay for Assessing Cellular Behavior of the Cranial Mesenchyme
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Mouse Tenm4 is required for mesoderm induction.

Hisashi Nakamura1, Rita N Cook, Monica J Justice

  • 1Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.

BMC Developmental Biology
|March 26, 2013
PubMed
Summary
This summary is machine-generated.

Tenm4 gene mutations prevent primitive streak formation and embryonic mesoderm development in mice. This failure in early development, observed before embryonic day 6.5, impacts Wnt signaling and cell differentiation.

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Area of Science:

  • Developmental Biology
  • Genetics
  • Molecular Biology

Background:

  • Tenm4 is a mouse homolog of Drosophila Tenascin-m, involved in motor neuron routing.
  • A genome-wide association study linked TENM4 to bipolar disorder susceptibility.
  • ENU mutagenesis generated Tenm4 mouse alleles with diverse phenotypes, necessitating further study.

Purpose of the Study:

  • To investigate the timing and characteristics of gastrulation failure in a loss-of-function Tenm4 allele.
  • To understand the role of Tenm4 in early embryonic development and mesoderm formation.

Main Methods:

  • Analysis of Tenm4 loss-of-function mutant embryos (Tenm4m1/m1).
  • Assessment of gene expression for mesoderm markers and axis patterning.
  • Cell proliferation assays and teratoma formation to evaluate pluripotency and differentiation capacity.
  • Analysis of epithelial-to-mesenchymal transition markers and Wnt signaling pathway activity (TOPGAL reporter).
  • Pharmacological rescue experiments using a GSK3β inhibitor.

Main Results:

  • Tenm4 mutant embryos failed to form a primitive streak and lacked embryonic mesoderm.
  • Expression of mesodermal genes and anteroposterior axis markers was absent or mislocalized.
  • Epiblast cells remained pluripotent but showed cell-autonomous differentiation defects, failing to form germ layer derivatives.
  • Impaired epithelial-to-mesenchymal transition and absent Wnt signaling were observed.
  • Partial rescue of embryonic development and Wnt signaling was achieved with a GSK3β inhibitor.

Conclusions:

  • Tenm4 is essential for primitive streak formation and embryonic mesoderm induction.
  • Defects in Tenm4 function lead to anterior-posterior patterning failures and cell-autonomous differentiation arrest.
  • Impairment occurs before embryonic day 6.5, resulting in Wnt signaling failure, though other pathways may also be involved.