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Related Experiment Video

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Light-mediated Reversible Modulation of the Mitogen-activated Protein Kinase Pathway during Cell Differentiation and Xenopus Embryonic Development
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A p38 MAPK-CREB pathway functions to pattern mesoderm in Xenopus.

Aviad Keren1, Anat Keren-Politansky, Eyal Bengal

  • 1Department of Biochemistry, Rappaport Institute for Research in the Medical Sciences, Faculty of Medicine, Technion-Israel Institute of Technology, P.O. Box 9649, Haifa 31096, Israel.

Developmental Biology
|August 5, 2008
PubMed
Summary

The p38 MAPK and CREB pathway regulates dorsal-ventral mesoderm patterning by controlling morphogen gradients. Differential activity of p38/CREB dictates cell fate decisions along the axis.

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Area of Science:

  • Developmental Biology
  • Cell Signaling

Background:

  • Dorsal-ventral patterning relies on morphogen gradients, but intracellular mechanisms for fate decisions are unclear.
  • Understanding how morphogen gradients are translated into cellular responses is crucial for developmental biology.

Purpose of the Study:

  • To investigate the intracellular signaling pathways involved in dorsal-ventral mesoderm patterning.
  • To elucidate the roles of p38 MAPK and CREB in translating morphogen gradients into cell fate decisions.

Main Methods:

  • Analyzing the distribution of phosphorylated CREB (S133) along the dorsal-ventral axis.
  • Investigating the effect of p38 MAPK pathway activation and CREB manipulation (knockdown and ectopic expression) on gene expression and mesoderm patterning.
  • Examining the relationship between p38/CREB and upstream signaling pathways (Wnt/beta-catenin, organizer genes) and downstream targets (chordin, vent1, Xmyf5).

Main Results:

  • Phosphorylated CREB (S133) forms a gradient along the dorsal-ventral mesoderm axis, mediated by p38 MAPK.
  • CREB knockdown disrupts chordin expression and dorsalization, while activated CREB induces these.
  • Modulating p38 MAPK or CREB activity can convert ventral mesoderm into a dorsal organizing center.
  • p38 MAPK and CREB function downstream of Wnt/beta-catenin and organizer genes.
  • Loss of p38 MAPK or CREB activity leads to ventral gene expansion and impaired lateral gene expression.

Conclusions:

  • Differential p38/CREB activity along the dorsal-ventral axis is a key regulator of mesoderm patterning.
  • The p38 MAPK/CREB pathway is essential for translating extracellular signals into specific cell fate decisions during embryonic development.