Hex expression suggests a role in the development and function of organs derived from foregut endoderm

Abstract

Hex is a divergent homeobox gene expressed as early as E4.5 in the mouse and in a pattern that suggests a role in anterior‐posterior patterning. Later in embryogenesis, Hex is expressed in the developing thyroid, lung, and liver. We now show Hex expression during thymus, gallbladder, and pancreas development and in the adult thyroid, lung, and liver. At E10.0, Hex is expressed in the 3rd pharyngeal pouch, from which the thymus originates, the endodermal cells of liver that are invading the septum transversum, the thyroid, the dorsal pancreatic bud, and gallbladder primoridum. At E13.5, expression is maintained at high levels in the thyroid, liver, epithelial cells lining the pancreatic and extrahepatic biliary ducts and is present in both the epithelial and mesenchymal cells of the lung. Expression in the thymus at this age is less than in the other organs. In the E16.5 embryo, expression persists in the thyroid, pancreatic, and bile duct epithelium, lung, and liver, with thymic expression dropping to barely detectable levels. By E18.5, expression in the thyroid and bile ducts remains high, whereas lung expression is markedly decreased. At this age, expression in the pancreas and thymus is no longer present. Finally, we show the cell types in the adult thyroid, lung, and liver that express Hex in the mature animal. Our results provide more detail on the potential role of Hex in the development of several organs derived from foregut endoderm and in the maintenance of function of several of these organs in the mature animal. © 2000 Wiley‐Liss, Inc.

Development of Liver and Pancreas

“…th day and continues to remain in the hepatocellular cell lines throughout the entire developmental period (24,25). In the accompaniment of appropriate signals, the hepatic diverticulum is transformed into hepatoblasts organized as cell cords.…”

Mutations in HHEX are not a common cause of monogenic forms of beta cell dysfunction

“…Mouse embryos lacking HHEX show a complete failure of ventral pancreatic specification [1] and have deletions of the forebrain, midbrain and rostral hindbrain [2]. HEX functions from very early in embryogenesis (E4.5) through adulthood and is involved in the regulation of genes at multiple developmental states, including mature tissue and cell type [3]. HHEX is expressed before the gene encoding the key pancreatic transcription factor, pancreatic and duodenal homeobox protein 1 (PDX1), and mouse embryos lacking HHEX do not express PDX1 in the ventral pancreas, whereas expression in the dorsal pancreas is unaffected [1].…”

The homeobox gene Hex induces T-cell-derived lymphomas when overexpressed in hematopoietic precursor cells

“…During mouse embryogenesis, Hex is first expressed in the primitive endoderm and subsequently in definitive endoderm (Thomas et al, 1998). Later expression is detectable in nascent blood islands in the visceral yolk sac and in endothelial cell precursors (Thomas et al, 1998) as well as in a variety of endoderm-derived organs (Bogue et al, 2000). Mouse embryos homozygous for Hex-null mutations die between 10.5 and 15.5 d.p.c with defects in liver, thyroid, and forebrain development as well as in monocyte development (Keng et al, 2000;MartinezBarbera et al, 2000).…”

“…Mouse embryos homozygous for Hex-null mutations die between 10.5 and 15.5 d.p.c with defects in liver, thyroid, and forebrain development as well as in monocyte development (Keng et al, 2000;MartinezBarbera et al, 2000). In the adult mouse, Hex expression can be detected in lung, liver, and thyroid (Bogue et al, 2000). In the hematopoietic system, Hex is expressed in pluripotent progenitor, erythromyeloid and B-cell lineages but not in T-cell lineages (Bedford et al, 1993;Manfioletti et al, 1995).…”