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Ephrin-B1 regulates axon guidance by reverse signaling through a PDZ-dependent mechanism

Jeffrey O Bush1, Philippe Soriano

  • 1Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.

Genes & Development
|June 12, 2009
PubMed

Insights

Ephrin-B1 reverse signaling is not essential for craniofacial and skeletal development. However, PDZ-dependent reverse signaling is critical for corpus callosum formation in mice.

Area of Science:

  • Developmental Biology
  • Molecular Biology
  • Genetics

Background:

  • Mutations in ephrin-B1 cause craniofrontonasal syndrome (CFNS), a disorder characterized by craniofacial, skeletal, and neurological abnormalities.
  • Ephrin-B1 participates in both forward signaling via EphB receptors and reverse signaling through PDZ-dependent or phosphorylation-dependent mechanisms.

Purpose of the Study:

  • To investigate the specific roles of ephrin-B1 reverse signaling pathways in development and congenital disease.
  • To determine how distinct reverse signaling mechanisms influence craniofacial, skeletal, and neurological development.

Main Methods:

  • Generated mice with targeted point mutations in ephrin-B1 to selectively disrupt PDZ-dependent or phosphorylation-dependent reverse signaling.
  • Maintained the capacity for ephrin-B1 forward signaling in mutant mice.
  • Analyzed craniofacial, skeletal, and corpus callosum development in genetically modified mice.

Main Results:

  • PDZ-dependent and phosphorylation-dependent reverse signaling by ephrin-B1 are not required for craniofacial and skeletal development.
  • PDZ-dependent reverse signaling by ephrin-B1 is essential for the formation of the corpus callosum, a major axon tract.
  • Ephrin-B1 reverse signaling acts autonomously in cortical axons to mediate avoidance of EphB2.

Conclusions:

  • PDZ-dependent reverse signaling of ephrin-B1 plays a crucial role in the development of the corpus callosum.
  • Ephrin-B1's developmental functions are partially mediated by its PDZ-dependent reverse signaling pathway.

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