Inactivation of Six2 in mouse identifies a novel genetic mechanism controlling development and growth of the cranial base

Guiyuan He, Sara Tavella, Karen Piper Hanley, Michelle Self, Guillermo Oliver, Raphaëlle Grifone, Neil Hanley, Christopher Ward, Nicoletta Bobola*

*Corresponding author for this work

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

The cranial base is essential for integrated craniofacial development and growth. It develops as a cartilaginous template that is replaced by bone through the process of endochondral ossification. Here, we describe a novel and specific role for the homeoprotein Six2 in the growth and elongation of the cranial base. Six2-null newborn mice display premature fusion of the bones in the cranial base. Chondrocyte differentiation is abnormal in the Six2-null cranial base, with reduced proliferation and increased terminal differentiation. Gain-of-function experiments indicate that Six2 promotes cartilage development and growth in other body areas and appears therefore to control general regulators of chondrocyte differentiation. Our data indicate that the main factors restricting Six2 function to the cranial base are tissue-specific transcription of the gene and compensatory effects of other Six family members. The comparable expression during human embryogenesis and the high protein conservation from mouse to human implicate SIX2 loss-of-function as a potential congenital cause of anterior cranial base defects in humans.

Original languageEnglish (US)
Pages (from-to)720-730
Number of pages11
JournalDevelopmental Biology
Volume344
Issue number2
DOIs
StatePublished - Aug 2010

Keywords

  • Cranial base
  • Development
  • Endochondral ossification
  • Mouse
  • Six2

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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