The role of the embryonic transcription factor,Pax-3
The role of the embryonic transcription factor,Pax-3
Pax-3 is a member of the Pax gene family of embryonic transcription factors that possess a conserved paired box motif coding for a 128 amino acid DNA binding domain called the paired domain. Pax proteins play important roles in vertebrate development. Pax-3 is expressed from embryonic day 8.5 in the developing central and peripheral nervous systems, as well as in developing limb muscle. Mutations in the Pax-3 gene give rise to developmental defects, characterised by the splotch phenotype in mice and Waardenburg Syndrome in humans. Abnormalities include spina bifida and exencephaly, limb deformities, pigmentation defects and loss of hearing. To further define the role that Pax-3 plays during embryogenesis, the regulation of Pax-3 activity was studied in the sensory neuron-derived cell line ND7. Attempts were also made to uncover novel molecular targets for Pax-3 in neuronal cells.
Expression of Pax-3 is restricted to undifferentiated ND7 cells, and is dependent on serum factors. Removal of serum leads to a rapid fall in Pax-3 mRNA expression, followed by cell cycle arrest and morphological differentiation. In the presence of 0.5% and 1% serum Pax-3 promoter activity was shown to decrease by the same amount as it did in the complete absence of serum, despite the fact that only 0% and 0.5% serum resulted in a decreased rate of ND7 cell proliferation. Therefore in neuronal cells the extent of cell proliferation may not be directly dependent on the level of Pax-3 transcription. In addition to peptide growth factors, serum lipids were shown to be necessary for the induction of Pax-3 promoter activity. The promoter may also undergo auto-regulation, as suggested by the fact that low levels of Pax-3 stimulated promoter activity whereas higher levels of Pax-3 repressed it. Pax-3 promoter activity was also modulated by Brn-3 proteins, which play important roles in neuronal cell differentiation.
University of Southampton
Bingham, Andrew John
54ab79a1-30ef-4967-ac0e-a35b0f0f6de2
2002
Bingham, Andrew John
54ab79a1-30ef-4967-ac0e-a35b0f0f6de2
Bingham, Andrew John
(2002)
The role of the embryonic transcription factor,Pax-3.
University of Southampton, Doctoral Thesis.
Record type:
Thesis
(Doctoral)
Abstract
Pax-3 is a member of the Pax gene family of embryonic transcription factors that possess a conserved paired box motif coding for a 128 amino acid DNA binding domain called the paired domain. Pax proteins play important roles in vertebrate development. Pax-3 is expressed from embryonic day 8.5 in the developing central and peripheral nervous systems, as well as in developing limb muscle. Mutations in the Pax-3 gene give rise to developmental defects, characterised by the splotch phenotype in mice and Waardenburg Syndrome in humans. Abnormalities include spina bifida and exencephaly, limb deformities, pigmentation defects and loss of hearing. To further define the role that Pax-3 plays during embryogenesis, the regulation of Pax-3 activity was studied in the sensory neuron-derived cell line ND7. Attempts were also made to uncover novel molecular targets for Pax-3 in neuronal cells.
Expression of Pax-3 is restricted to undifferentiated ND7 cells, and is dependent on serum factors. Removal of serum leads to a rapid fall in Pax-3 mRNA expression, followed by cell cycle arrest and morphological differentiation. In the presence of 0.5% and 1% serum Pax-3 promoter activity was shown to decrease by the same amount as it did in the complete absence of serum, despite the fact that only 0% and 0.5% serum resulted in a decreased rate of ND7 cell proliferation. Therefore in neuronal cells the extent of cell proliferation may not be directly dependent on the level of Pax-3 transcription. In addition to peptide growth factors, serum lipids were shown to be necessary for the induction of Pax-3 promoter activity. The promoter may also undergo auto-regulation, as suggested by the fact that low levels of Pax-3 stimulated promoter activity whereas higher levels of Pax-3 repressed it. Pax-3 promoter activity was also modulated by Brn-3 proteins, which play important roles in neuronal cell differentiation.
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Published date: 2002
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Local EPrints ID: 464806
URI: http://eprints.soton.ac.uk/id/eprint/464806
PURE UUID: c62731b8-a024-46d0-b8f7-682caed61b0d
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Date deposited: 05 Jul 2022 00:02
Last modified: 16 Mar 2024 19:45
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Author:
Andrew John Bingham
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