title: Distinct enhancers at the Pax3 locus can function redundantly to regulate neural tube and neural crest expressions.
abstract: Pax3 is a transcription factor expressed in somitic mesoderm, dorsal neural tube and pre-migratory neural crest during embryonic development. We have previously identified cis-acting enhancer elements within the proximal upstream genomic region of Pax3 that are sufficient to direct functional expression of Pax3 in neural crest. These elements direct expression of a reporter gene to pre-migratory neural crest in transgenic mice, and transgenic expression of a Pax3 cDNA using these elements is sufficient to rescue neural crest development in mice otherwise lacking endogenous Pax3. We show here that deletion of these enhancer sequences by homologous recombination is insufficient to abrogate neural crest expression of Pax3 and results in viable mice. We identify a distinct enhancer in the fourth intron that is also capable of mediating neural crest expression in transgenic mice and zebrafish. Our analysis suggests the existence of functionally redundant neural crest enhancer modules for Pax3.
authors.affiliation: Division of Cardiology, Department of Pediatrics, Children's Hospital of Philadelphia, PA, USA.
authors.forename: Karl R
authors.initials: KR
authors.lastname: Degenhardt
authors.forename: Rita C
authors.initials: RC
authors.lastname: Milewski
authors.forename: Arun
authors.initials: A
authors.lastname: Padmanabhan
authors.forename: Mayumi
authors.initials: M
authors.lastname: Miller
authors.forename: Manvendra K
authors.initials: MK
authors.lastname: Singh
authors.forename: Deborah
authors.initials: D
authors.lastname: Lang
authors.forename: Kurt A
authors.initials: KA
authors.lastname: Engleka
authors.forename: Meilin
authors.initials: M
authors.lastname: Wu
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.forename: Diane
authors.initials: D
authors.lastname: Zhou
authors.forename: Nicole
authors.initials: N
authors.lastname: Antonucci
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Epstein
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D004622:Embryo, Mammalian / Q000378:metabolism; D004625:Embryo, Nonmammalian / Q000378:metabolism; D004742:Enhancer Elements, Genetic / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D008822:Mice, Transgenic; D009432:Neural Crest / Q000196:embryology*; D054259:Neural Tube / Q000196:embryology*; D051761:Paired Box Transcription Factors / Q000235:genetics* / Q000378:metabolism; D015027:Zebrafish / Q000196:embryology
chemical_list: D051761:Paired Box Transcription Factors