Cdx gene deficiency compromises embryonic hematopoiesis in the mouse

• DOI: 10.1073/pnas.0708951105
• Publication Date: 2008-05-30T00:54:44Z
• Authors: Yuan Wang; Akiko Yabuuchi; Shannon McKinney-...; Danica M. K. Duch...; Manas K. Ray; Kallayanee Chawen...; Trevor K. Archer; George Q. Daley
• Keywords: Homeodomain Proteins; Mice, Knockout; 0301 basic medicine; embryoid body; Embryo, Mammalian; Hematopoietic Stem Cells; embryonic stem cell; Hematopoiesis; Hox genes; Mice; 03 medical and health sciences; C1; A-P patterning; 970106 Expanding Knowledge in the Biological Sciences; Animals; CDX2 Transcription Factor; 270202 Genome Structure; development; Embryonic Stem Cells; Transcription Factors

Cdx genes ( Cdx1 , Cdx2 , and Cdx4 ) encode a family of caudal -related transcription factors that mediate anterior–posterior patterning during embryogenesis through Hox gene regulation. Homologues in the zebrafish have been shown to play key roles in blood formation. To define the role of Cdx genes during embryonic hematopoiesis in a mammalian system, we examined the hematopoietic potential of Cdx -deficient mouse embryonic stem cells (ESCs) in vitro and in vivo . Individual Cdx -deficient ESCs exhibited impaired embryonic hematopoietic progenitor formation and altered Hox gene expression, most notably for Cdx2 deficiency. A more severe hematopoietic defect was observed with compound Cdx deficiency than loss of function of any single Cdx gene. Reduced hematopoietic progenitor formation of ESCs deficient in multiple Cdx genes could be rescued by ectopic expression of Cdx4 , concomitant with partially restored Hox gene expression. These results reveal an essential and partially redundant role for multiple Cdx genes during embryonic hematopoiesis in the mouse.