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Gastrulation01:56

Gastrulation

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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...
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TGF - β Signaling Pathway01:16

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The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
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Hedgehog Signaling Pathway02:33

Hedgehog Signaling Pathway

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The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...
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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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Role Of Notch Signalling In Intestinal Stem Cell Renewal01:12

Role Of Notch Signalling In Intestinal Stem Cell Renewal

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Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
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Related Experiment Video

Updated: Sep 17, 2025

A Rapid In Vivo Bioassay for Developmentally Active Enhancers
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Gastrula-Premarked Posterior Enhancer Primes Posterior Tissue Development Through Cross-Talk with TGF-β Signaling

Yingying Chen1, Fengxiang Tan1, Qing Fang2

  • 1Guangzhou National Laboratory, Guangzhou International Bio Island, No. 9 XingDaoHuanBei Road, Guangzhou, Guangdong Province, 510005, China.

Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|June 30, 2025
PubMed
Summary

A novel enhancer, p-Enh, regulates mouse embryonic posterior development by modulating Cdx2 and TGF-β signaling via enhancer RNAs (eRNAs). Its disruption causes embryonic lethality, highlighting its crucial role in cell fate determination.

Keywords:
Pre‐marked enhancerTGF‐β signalingenhancer RNAposterior tissue development

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Area of Science:

  • Developmental Biology
  • Epigenetics
  • Molecular Biology

Background:

  • Cell fate determination and lineage diversification in mammalian embryonic development are complex and not fully understood.
  • Regulatory paradigms governing these processes require further elucidation.

Purpose of the Study:

  • To identify and characterize novel regulatory elements controlling mammalian embryonic posterior tissue development.
  • To investigate the molecular mechanisms underlying the function of a newly identified enhancer, p-Enh.

Main Methods:

  • Epigenetic landscape analysis of mouse gastrula.
  • Morphological and single-cell transcriptomic analyses of p-Enh knockout (KO) embryos.
  • Investigation of enhancer RNA (eRNA) production and function.
  • Analysis of interactions between eRNAs and proteins (SMAD4).
  • In vitro gastruloid experiments to assess rescue mechanisms.

Main Results:

  • p-Enh, located in the first intron of Cdx2, is epigenetically marked in the primitive streak region.
  • p-Enh knockout embryos exhibit embryonic lethality with disrupted posterior development.
  • p-Enh regulates Cdx2 in cis and modulates global transcriptome/epigenome via trans-acting eRNAs.
  • p-Enh-derived eRNAs interact with SMAD4, participating in TGF-β signaling.
  • Combined modulation of TGF-β signaling and p-Enh-eRNA abundance rescues posterior development defects in gastruloids.

Conclusions:

  • p-Enh is a critical regulator of posterior tissue development in mouse embryos.
  • p-Enh-derived eRNAs act as cross-modular coordinators, influencing TGF-β signaling and priming posterior development.
  • A novel regulatory model involving enhancer RNAs in mammalian embryonic development is proposed.