"Developmental studies of the murine homeobox gene - hoxa-9”

Abstract

Cell patterning during embryogenesis is essential for establishing the identity of the developing body plan. Hox genes are fundamental regulators of tissue organisation along the anterior-posterior body axis of the developing embryo. These homeodomain-containing proteins act as transcription factors during normal development. The function of the homeodomain is to bind sequence-specific DNAmotifs which allows either activation or repression of downstream effector genes, which consequently results in the control of tissue-specific determination and differentiation. Aberrant expression of such Hox genes, including Hoxa-9 can result in homeotic transformations leading to phenotypic malformations and oncogenesis. However the normal function of Hoxa-9 is poorly understood. This study explored the potential role for Hoxa-9 in normal development and differentiation. An in situ hybridisation approach was taken to define the expression of Hoxa-9 in the developing mouse. Hoxa-9 was found to expressed in a temporarily and spatially regulated manner, in particular being detected in the developing cardiac atria, ventricles and cardiac vessels during E9.5-E12 stages of development. The expression of this homeotic gene during in vitro differentiation of embryonic stem cells into cardiomyocytes and haematopoietic cells demonstrated a profile that correlated with the emergence of these cell types. The functioning relationship between Hoxa-9 expression and lineage commitment was Airther explored using over-expression in embryonic stem cells. A potential role for Hoxa-9 in normal development is discussed.