Volume 1266, Issue 1 p. 47-54

Caudal genes in blood development and leukemia

Claudia Lengerke

Claudia Lengerke

University of Tübingen Medical Center—Hematology & Oncology, Tübingen, Germany.

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George Q. Daley

George Q. Daley

Children's Hospital Boston and Dana Farber Cancer Institute—Stem Cell Transplantation Program, Boston, Massachusetts

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First published: 17 August 2012
Citations: 14
Dr. George Daley, Children's Hospital Boston and Dana Farber Cancer Institute—Stem Cell Transplantation Program, 300 Longwood Avenue, Boston, MA 02115. [email protected]; or Dr. Claudia Lengerke, University of Tübingen Medical Center—Hematology & Oncology, Otfried-Mueller-Strasse 10, 72076 Tübingen, Germany. [email protected]

Abstract

Members of the caudal gene family (in mice and humans: Cdx1, Cdx2, and Cdx4) have been studied during early development as regulators of axial elongation and anteroposterior patterning. In the adult, Cdx1 and Cdx2, but not Cdx4, have been intensively explored for their function in intestinal tissue homeostasis and the pathogenesis of gastrointestinal cancers. Involvement in embryonic hematopoiesis was first demonstrated in zebrafish, where cdx genes render posterior lateral plate mesoderm competent to respond to genes specifying hematopoietic fate, and compound mutations in cdx genes thus result in a bloodless phenotype. Parallel studies performed in zebrafish embryos and murine embryonic stem cells (ESCs) delineate conserved pathways between fish and mammals, corroborating a BMP/Wnt-Cdx-Hox axis during blood development that can be employed to augment derivation of blood progenitors from pluripotent stem cells in vitro. The molecular regulation of Cdx genes appears complex, as more recent data suggest involvement of non-Hox–related mechanisms and the existence of auto- and cross-regulatory loops governed by morphogens. Here, we will review the role of Cdx genes during hematopoietic development by comparing effects in zebrafish and mice and discuss their participation in malignant blood diseases.