Identification of minimal enhancer elements sufficient for Pax3 expression in neural crest and implication of Tead2 as a regulator of Pax3
2004
Pax3 is a transcription factor that is required by Pre-migratory neural
crest cells give rise to the peripheral nervous system, melanocytes, some
vascular smooth muscle, and numerous other derivatives. These cells require
the transcription factor Pax3, and both mice and humans with Pax3 deficiency
exhibit neural crest-related developmental defects. Pax3 is also expressed in
the dorsal neural tube, and by myogenic progenitors in the presomitic mesoderm
and the hypaxial somites. Molecular pathways that regulate Pax3
expression in the roof plate probably represent early upstream signals in
neural crest induction. We have identified an enhancer region in the
Pax3 genomic locus that is sufficient to recapitulate expression in
neural crest precursors in transgenic mice. We show that Tead2, a member of
the Tead box family of transcription factors, binds to a neural crest enhancer
and activates Pax3 expression. Tead2, and its co-activator YAP65, are
co-expressed with Pax3 in the dorsal neural tube, and mutation of the
Tead2 binding site in the context of Pax3 transgenic constructs
abolishes neural expression. In addition, a Tead2-Engrailed fusion protein is
able to repress retinoic acid-induced Pax3 expression in P19 cells
and in vivo. These results suggest that Tead2 is an endogenous activator of
Pax3 in neural crest.
Keywords:
- Correction
- Source
- Cite
- Save
- Machine Reading By IdeaReader
40
References
91
Citations
NaN
KQI