In situ hybridization studies suggest a role for the basic region‐leucine zipper protein hXBP‐1 in exocrine gland and skeletal development during mouse embryogenesis

Abstract

The spatial and temporal distribution of transcripts for the TREERE-binding basic region-leucine zipper protein hXBP-1 was determined by in situ hybridization. Analysis of embryos from day 10.5 to 18.5 pc revealed high level expression of hXBP-1 RNA in two developing organ systems: 1) in bone and cartilage cells of the developing skeleton and toothbuds, and 2) in exocrine glands including the pancreas and the submandibular and salivary glands. High level expression was also found in whisker follicles and in selected cells in brown adipose tissue. In the developing skeleton, hXBP-1 RNA was expressed starting on day 11.5 pc in osteoblasts of newly formed intramembranous bone. Thereafter, hXBP-1 was expressed in both osteoblasts and preosteoblasts in bone formed directly by intramembranous formation as well as in bone formed during endochondral ossification. The most intense signal was observed in preosteoblasts and osteoblasts of newly forming bone. At day 11.5 pc low level hXBP-1 expression was also observed in matrix secreting chondroblasts of bones which are formed initially of cartilage, at the stage where they consist entirely of cartilage. Signal was also present in matrix producing chondroblasts of the mature zone of the growth region during endochondral ossification although at significantly lower level than in osteoblasts. hXBP-1 is thus the first transcription factor described, to our knowledge, whose level of expression is modulated during the osteoblast developmental sequence in vivo. The pattern of expression of hXBP-1 in the developing skeleton was found to be very similar to that of the genes encoding the tissue inhibitor of metalloproteinase and alkaline phosphatase throughout development. These observations suggest that hXBP-1 may play a role in regulating the expression of tissue specific genes (TIMP, osteonectin, osteopontin, osteocalcin) expressed in osteoblasts. It is intriguing that the promoter regions of several such genes contain po-

Cellular response to endoplasmic reticulum stress: a matter of life or death

“…62,63 XBP-1 mRNA is ubiquitous in adult tissues but preferentially expressed in the fetal exocrine glands, osteoblasts, chondroblasts and liver. 64 Like HAC1, newly synthesized XBP-1 transcript must be spliced by activated Ire1 to a mature, efficiently translated mRNA. 62,63 When activated by ER stress, Ire1 excises an intron from the immature XBP-1 transcript, resulting in the replacement of the C-terminal domain of the protein and the translational activation of the mRNA, analogous to the splicing of HAC1 mRNA.…”

Signal Transduction Pathways Mediating Parathyroid Hormone Stimulation of Bone Sialoprotein Gene Expression in Osteoblasts

“…Finally, there have been several studies that have shown an increased expression of c-fos in bone from patients with fibrous dysplasia, in which there is an overexpression or ectopic expression of bone formation (20). In a number of recent studies, members of the basic leucine zipper protein family, including c-fos (21,22), hXBP (23), and ATF2 (24) have been shown to be expressed selectively during normal skeletal tissue development. Finally, in recent studies, the ablation of one of these factors, ATF2, led to a defect in endochondral ossification, which has a similar histopathology to human hypochondroplasia (24).…”

Expression patterns among interferon regulatory factor-1, human X-box binding protein-1, nuclear factor kappa B, nucleophosmin, estrogen receptor-alpha and progesterone receptor proteins in breast cancer tissue microarrays

“…As a member of the ATF/CREB transcription factor family that activate promoters containing specific cyclic AMP responsive elements (CRE) (33), hXBP-1 regulates the expression of several tissue-specific genes, including tissue inhibitor of metalloproteinases, osteopontin and osteocalcin (34). Potentially downstream of NFκB activation in some cells (35), hXBP-1 is associated with increased proliferation and reduced apoptosis (16), which implies a survival function.…”