Hyaluronan Synthase Gene Expression

Numerous studies have indicated that Has2 is the key gene with respect to the bulk of the HA biosynthesis that occurs in mammals (13-17). Has2 is expressed broadly during mouse embryogenesis, correlating with all previously described spatial and temporal localizations for HA ((18) and Tien and Spicer, manuscript in preparation). These include the endocardial cushions of the developing heart, craniofacial mesenchyme, precartilage areas, hypertrophic chondrocytes, neural crest cells and their derivatives (Fig. 1A). In contrast, Has1 is expressed only during gastrulation (E7.5-E8.5) in a more general pattern (data not shown), and Has3 is expressed only by the mesenchymal component of developing teeth and hair (Fig. 1B-F). Both teeth and hair develop through strong interactions between epithelial cells and mesenchymal cells (20). Within each developing hair follicle, Has3 expression is transient, correlating with the timing of condensation. In contrast, Has3 expression is detectable as early as E10.5 in tooth-forming cephalic crest and expression is maintained in the tooth-forming mesenchyme until at least the bell-stage of development.

Figure 1 Expression of Has2 and Has3 in the developing mouse embryo. Whole-mount in situ hybridization was carried out essentially using published procedures (19) with digoxigenin-labeled antisense RNA probes for mouse Has2 or mouse Has3 or the equivalent sense probes. Colorimetric detection was employed. (A) Has2 expression was observed in neural crest cell populations and the endocardial cushions at E9.5. Branchial arches 1-6 are numbered. (B) and (C) Has3 is expressed within developing whisker and hair follicles in a transient fashion. (D)-(F) Has3 is expressed by tooth-forming cephalic neural crest cells within the first branchial arch at E10.5. Arrows indicate the areas of tooth-forming cephalic neural crest cells that are positive for Has3 expression. (F) Cartoon depiction of an E10.5 mouse embryo. The dashed line indicates the plane at which the embryos were cut to view the positive in situ signal in the maxillary (D) and mandibular (E) components of the first branchial arch. EC, endocardial cushions; PNP, posterior neuropore.

Figure 1 Expression of Has2 and Has3 in the developing mouse embryo. Whole-mount in situ hybridization was carried out essentially using published procedures (19) with digoxigenin-labeled antisense RNA probes for mouse Has2 or mouse Has3 or the equivalent sense probes. Colorimetric detection was employed. (A) Has2 expression was observed in neural crest cell populations and the endocardial cushions at E9.5. Branchial arches 1-6 are numbered. (B) and (C) Has3 is expressed within developing whisker and hair follicles in a transient fashion. (D)-(F) Has3 is expressed by tooth-forming cephalic neural crest cells within the first branchial arch at E10.5. Arrows indicate the areas of tooth-forming cephalic neural crest cells that are positive for Has3 expression. (F) Cartoon depiction of an E10.5 mouse embryo. The dashed line indicates the plane at which the embryos were cut to view the positive in situ signal in the maxillary (D) and mandibular (E) components of the first branchial arch. EC, endocardial cushions; PNP, posterior neuropore.

All Has genes are expressed to varying degrees in adult tissues (9). In contrast to the limited expression of Hasl in the embryo, this gene is the most widely expressed in adult tissues and is even expressed by various immune cells, including dendritic cells and activated T-cells (21). Has3 is also broadly expressed and appears to be the dominant HA synthase expressed in the epidermis (22). Has2 is expressed in a more restricted spatial pattern in the adult, but is the dominant HA synthase in the dermis (Spicer, unpublished data), cumulus cells of the ovary (23) and growth plate cartilage (16,24). Has2 is also the target for induction by many growth factors, proinflammatory cytokines and chemokines. These include members of the TGF-b/BMP superfamily, EGF, KGF, IL-1b and TNF-a (13-15,17,25-27). In addition, Has2 expression can be rapidly suppressed by glucocorticoids (13,28). In this regard, suppression of Has2

mRNAs and loss of HA biosynthesis may be part of the underlying pathology observed in long-term glucocorticoid treatment of humans. These patients often suffer from dermal thinning and bone loss/atrophy. Has3 can also be induced by various factors, including EGF, KGF, proinflammatory cytokines, interferon-gamma and mechanical stimulation (17,22,26,27,29). The Has3 gene has alternate exon 1s, with presumed alternate promoters (12,22). The respective expression domains for the alternate Has3 mRNAs are not understood at this time.

10 Ways To Fight Off Cancer

10 Ways To Fight Off Cancer

Learning About 10 Ways Fight Off Cancer Can Have Amazing Benefits For Your Life The Best Tips On How To Keep This Killer At Bay Discovering that you or a loved one has cancer can be utterly terrifying. All the same, once you comprehend the causes of cancer and learn how to reverse those causes, you or your loved one may have more than a fighting chance of beating out cancer.

Get My Free Ebook


Post a comment