How does Fgf signaling from the isthmic organizer induce midbrain and cerebellum development?

Authors

  • Tatsuya Sato,

    Corresponding author
    1. Howard Hughes Medical Institute and Developmental Genetics Program, Skirball Institute of Biomolecular Medicine, Department of
    2. Cell Biology and
    Search for more papers by this author
  • Alexandra L. Joyner,

    1. Howard Hughes Medical Institute and Developmental Genetics Program, Skirball Institute of Biomolecular Medicine, Department of
    2. Cell Biology and
    3. Physiology & Neuroscience, New York University School of Medicine, New York, NY10016, USA and
    Search for more papers by this author
  • Harukazu Nakamura

    1. Department of Molecular Neurobiology, Graduate School of Life Sciences and Institute of Development, Aging and Cancer, Tohoku University, Seiryo-machi 4–1, Aoba-ku, Sendai 980–8575, Japan
    Search for more papers by this author

*Author to whom all correspondence should be addressed.
Email: sato@saturn.med.nyu.edu

Abstract

The mesencephalic/rhombomere 1 border (isthmus) is an organizing center for early development of midbrain and cerebellum. In this review, we summarize recent progress in studies of Fgf signaling in the isthmus and discuss how the isthmus instructs the differentiation of the midbrain versus cerebellum. Fgf8 is shown to play a pivotal role in isthmic organizer activity. Only a strong Fgf signal mediated by Fgf8b activates the Ras-extracellular signal-regulated kinase (ERK) pathway, and this is sufficient to induce cerebellar development. A lower level of signaling transduced by Fgf8a, Fgf17 and Fgf18 induce midbrain development. Numerous feedback loops then maintain appropriate mesencephalon/rhombomere1 and organizer gene expression.

Ancillary