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Stressful development: integrating endoderm development, stress, and longevity.

Chee Kiang Ewe1, Geneva Alok1, Joel H Rothman1

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Area of Science:

  • Developmental Biology
  • Genetics
  • Molecular Biology

Background:

  • The intestine is a vital organ for digestion, nutrient absorption, and host defense against environmental stressors.
  • The gene regulatory network (GRN) controlling endoderm and intestine development is well-studied in C. elegans.
  • The SKN-1 transcription factor, an Nrf1/2 ortholog, is crucial for initiating embryonic GRN activation and mediates stress responses.

Purpose of the Study:

  • To review the intersection between genetic nodes regulating endoderm/intestine differentiation and stress/homeostasis.
  • To explore how intestine-to-germline signaling influences heritable epigenetic changes and adaptive stress responses.
  • To understand how selective pressures on stress response pathways shape endoderm GRN architecture.

Main Methods:

  • Literature review of existing research on gene regulatory networks, stress response, innate immunity, aging, and epigenetics.
  • Analysis of conserved regulatory roles of transcription factors like SKN-1/Nrf1/2 across metazoan phylogeny.
  • Discussion of signaling pathways connecting intestinal development to germline and transgenerational inheritance.

Main Results:

  • Key regulatory factors in gut development are also involved in stress response, innate immunity, aging, and longevity.
  • Intestine-to-germline signaling, involving SKN-1, can mediate heritable epigenetic changes for adaptive stress responses.
  • Connections exist between endoderm/intestine development regulation and stress response mechanisms.

Conclusions:

  • The interplay between intestinal development and stress response pathways suggests evolutionary links.
  • Variations in selective pressures on stress response pathways can influence the structure of the endoderm GRN.
  • This can lead to genetic and epigenetic variations in early embryonic GRN regulatory events, impacting organismal adaptation.