Reference : Notochord-dependent expression of MFH1 and PAX1 cooperates to maintain the proliferat...
Scientific journals : Article
Life sciences : Genetics & genetic processes
Notochord-dependent expression of MFH1 and PAX1 cooperates to maintain the proliferation of sclerotome cells during the vertebral column development.
Furumoto, T. A. [> >]
Miura, N. [> >]
Akasaka, T. [> >]
Mizutani-Koseki, Y. [> >]
Sudo, H. [> >]
Fukuda, K. [> >]
Maekawa, M. [> >]
Yuasa, S. [> >]
Fu, Y. [> >]
Moriya, H. [> >]
Taniguchi, M. [> >]
Imai, K. [> >]
Dahl, E. [> >]
Balling, Rudi mailto []
Pavlova, M. [> >]
Gossler, A. [> >]
Koseki, H. [> >]
Developmental Biology
Yes (verified by ORBilu)
[en] Animals ; Cell Division ; Chick Embryo ; DNA-Binding Proteins/genetics/metabolism ; Forkhead Transcription Factors ; Gene Expression Regulation, Developmental/genetics ; Hedgehog Proteins ; Histocytochemistry ; Immunohistochemistry ; In Situ Hybridization ; Meningomyelocele/genetics ; Mice ; Mutation ; Myogenin/metabolism ; Notochord/embryology/metabolism ; PAX9 Transcription Factor ; Paired Box Transcription Factors ; Proteins/genetics ; Signal Transduction ; Spinal Dysraphism/genetics ; Spine/embryology ; Trans-Activators ; Transcription Factors/genetics/metabolism
[en] During axial skeleton development, the notochord is essential for the induction of the sclerotome and for the subsequent differentiation of cartilage forming the vertebral bodies and intervertebral discs. These functions are mainly mediated by the diffusible signaling molecule Sonic hedgehog. The products of the paired-box-containing Pax1 and the mesenchyme forkhead-1 (Mfh1) genes are expressed in the developing sclerotome and are essential for the normal development of the vertebral column. Here, we demonstrate that Mfh1 like Pax1 expression is dependent on Sonic hedgehog signals from the notochord, and Mfh1 and Pax1 act synergistically to generate the vertebral column. In Mfh1/Pax1 double mutants, dorsomedial structures of the vertebrae are missing, resulting in extreme spina bifida accompanied by subcutaneous myelomeningocoele, and the vertebral bodies and intervertebral discs are missing. The morphological defects in Mfh1/Pax1 double mutants strongly correlate with the reduction of the mitotic rate of sclerotome cells. Thus, both the Mfh1 and the Pax1 gene products cooperate to mediate Sonic hedgehog-dependent proliferation of sclerotome cells.
Copyright 1999 Academic Press.

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