title: Cdx1 and Cdx2 are functionally equivalent in vertebral patterning.
abstract: The Cdx transcription factors regulate anterior-posterior (AP) vertebral patterning, at least in part, through direct regulation of Hox gene expression. Analysis of allelic series of Cdx mutant mice suggests functional overlap between these family members. However, the lack of a Cdx2 null mutant makes these analyses incomplete. Moreover, Hox proteins are sometimes redundant, making it difficult to discern whether Cdx members regulate identical Hox target genes in a redundant manner, or whether they regulate separate Hox genes which then converge on events related to vertebral patterning. To more directly assess this question, we developed a "knock in" model whereby Cdx2 was substituted for Cdx1. Consistent with functional redundancy Cdx2 "knock-in" mice exhibited perfect complementation of the Cdx1-null phenotype, as evidenced by the lack of skeletal defects or altered expression of Hox genes typically impacted by Cdx1 loss-of-function. It has been proposed that vertebral AP patterning is reliant on a gradient of the sum total of Cdx proteins, a posit that is consistent with functional redundancy between Cdx family members. To further assess this, we generated a gain-of-function model using BAC transgenesis to alter Cdx1 dosage. Cdx1 BAC transgenic mice overexpressed Cdx1 mRNA and protein, and fully complemented the Cdx1 null allele. However, gain of Cdx1 dosage via this BAC transgene in an otherwise wild type background had no discernible effects on vertebral patterning or Hox gene expression, suggesting that a moderate alteration in the Cdx protein gradient is of no consequence.
authors.affiliation: Department of Cellular and Molecular Medicine, University of Ottawa, 451 Smyth Road, Ottawa, Ontario, Canada.
authors.forename: Joanne G A
authors.initials: JG
authors.lastname: Savory
authors.forename: Nicolas
authors.initials: N
authors.lastname: Pilon
authors.forename: Stephanie
authors.initials: S
authors.lastname: Grainger
authors.forename: Jean-René
authors.initials: JR
authors.lastname: Sylvestre
authors.forename: Mélanie
authors.initials: M
authors.lastname: Béland
authors.forename: Martin
authors.initials: M
authors.lastname: Houle
authors.forename: Karen
authors.initials: K
authors.lastname: Oh
authors.forename: David
authors.initials: D
authors.lastname: Lohnes