SOX3 is required during the formation of the hypothalamo-pituitary axis

Nat Genet. 2004 Mar;36(3):247-55. doi: 10.1038/ng1309. Epub 2004 Feb 15.


The pituitary develops from the interaction of the infundibulum, a region of the ventral diencephalon, and Rathke's pouch, a derivative of oral ectoderm. Postnatally, its secretory functions are controlled by hypothalamic neurons, which also derive from the ventral diencephalon. In humans, mutations affecting the X-linked transcription factor SOX3 are associated with hypopituitarism and mental retardation, but nothing is known of their etiology. We find that deletion of Sox3 in mice leads to defects of pituitary function and of specific central nervous system (CNS) midline structures. Cells in the ventral diencephalon, where Sox3 is usually highly expressed, have altered properties in mutant embryos, leading to abnormal development of Rathke's pouch, which does not express the gene. Pituitary and hypothalamic defects persist postnatally, and SOX3 may also function in a subset of hypothalamic neurons. This study shows how sensitive the pituitary is to subtle developmental defects and how one gene can act at several levels in the hypothalamic-pituitary axis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Morphogenetic Protein 4
  • Bone Morphogenetic Proteins / metabolism
  • DNA-Binding Proteins / genetics*
  • Diencephalon / embryology
  • Fibroblast Growth Factor 8
  • Fibroblast Growth Factors
  • High Mobility Group Proteins / genetics*
  • Hypothalamo-Hypophyseal System / embryology*
  • Mice
  • Mice, Transgenic
  • Mutation
  • Pituitary Gland / embryology
  • SOXB1 Transcription Factors
  • Transcription Factors / genetics*
  • X Chromosome


  • BMP4 protein, human
  • Bmp4 protein, mouse
  • Bone Morphogenetic Protein 4
  • Bone Morphogenetic Proteins
  • DNA-Binding Proteins
  • Fgf8 protein, mouse
  • High Mobility Group Proteins
  • SOX3 protein, human
  • SOXB1 Transcription Factors
  • Sox3 protein, mouse
  • Transcription Factors
  • Fibroblast Growth Factor 8
  • Fibroblast Growth Factors