Fgf8 signaling for development of the midbrain and hindbrain

Dev Growth Differ. 2016 Jun;58(5):437-45. doi: 10.1111/dgd.12293. Epub 2016 Jun 7.


In this paper, we review how midbrain and hindbrain are specified. Otx2 and Gbx2 are expressed from the early phase of development, and their expression abuts at the midbrain hindbrain boundary (MHB), where Fgf8 expression is induced, and functions as an organizing molecule for the midbrain and hindbrain. Fgf8 induces En1 and Pax2 expression at the region where Otx2 is expressed to specify midbrain. Fgf8 activates Ras-ERK pathway to specify hindbrain. Downstream of ERK, Pea3 specifies isthmus (rhombomere 0, r0), and Irx2 may specify r1, where the cerebellum is formed.

Keywords: Fgf8 signaling; Pea3; Ras-ERK; hindbrain; isthmus; midbrain.

Publication types

  • Review

MeSH terms

  • Animals
  • Fibroblast Growth Factor 8 / biosynthesis*
  • Fibroblast Growth Factor 8 / genetics
  • Gene Expression Regulation, Developmental / physiology*
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism
  • Humans
  • MAP Kinase Signaling System / physiology*
  • Mesencephalon / embryology*
  • Otx Transcription Factors / genetics
  • Otx Transcription Factors / metabolism
  • PAX2 Transcription Factor / genetics
  • PAX2 Transcription Factor / metabolism
  • Rhombencephalon / embryology*


  • EN1 protein, human
  • FGF8 protein, human
  • Homeodomain Proteins
  • OTX2 protein, human
  • Otx Transcription Factors
  • PAX2 Transcription Factor
  • PAX2 protein, human
  • Fibroblast Growth Factor 8