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From the Division of Cardiovascular Research (H.A.S., G.S., R.C.S., V.A., J.I., K.W.), St. Elizabeth's Medical Center and Tufts University School of Medicine, Boston, Mass; the Cardiac Unit (H.A.S.), Massachusetts General Hospital, Boston; the Department of Anatomy (G.E.L.), University of Wisconsin Medical School, Madison; and the Department of Cardiovascular Research (S.S.), Berlex Biosciences, Richmond, Calif.
Correspondence to Kenneth Walsh, PhD, Division of Cardiovascular Research, St. Elizabeth's Medical Center, 736 Cambridge St, Boston, MA 02135. E-mail kwalsh{at}OPAL.TUFTS.EDU
Abstract Gax is a homeobox-containing gene that has been detected in adult cardiovascular tissues and exhibits a growth arrestspecific pattern of expression in cultured vascular myocytes. To study the regulation of gax during development, we performed immunohistochemistry and in situ hybridization on mouse embryos. Gax was present in mesodermally and, as with other homeobox genes, neuroectodermally derived tissues. Early mesodermal protein expression was limited to the lateral plate and somitic mesoderm. Gax in the cardiac muscle lineage exhibited a biphasic pattern of expression. Expression was prominent in the heart tube of the earliest cardiomyocytes and remained prominent through the looping stage (day 12.5 post coitum [pc]) but fell below the threshold of detection in atria and ventricles by day 13.5 pc. At day 15.5 pc, Gax protein was again detectable but restricted to cells within the compact layer of the ventricular myocardium. Gax expression was also noted in smooth muscle cells as early as day 9.5 pc. In the skeletal muscle lineage, Gax protein was expressed at the onset of somitogenesis before the expression of the myogenic basic helix-loop-helix and MEF2/RSRF family proteins. Subsequently, it was noted at day 9.5 pc in premyogenic cells migrating into head, trunk, and limb buds. Gax was detected in myotomes, premuscle masses, and mature muscle groups. These data suggest an important developmental role for Gax in all muscle lineages.
Key Words: homeobox gene Gax cardiac muscle smooth muscle skeletal muscle
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