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Expression of transmembrane carbonic anhydrases, CAIX and CAXII, in human development.

Liao SY, Lerman MI, Stanbridge EJ - BMC Dev. Biol. (2009)

Bottom Line: Co-localization of CAXII with CAIX or HIF-1alpha was not observed.The study has showed that: 1) HIF-1alpha and CAIX expression co- localized in many, but not all, of the embryonic and early fetal tissues; 2) There is no evidence of co-localization of CAIX and CAXII; 3) CAIX and CAXII expression is closely related to cell origin and secretory activity involving proton transport, respectively.The intriguing finding of rare CAIX-expressing cells in those sites corresponding to stem cell niches requires further investigation.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pathology, St. Joseph Hospital, Orange, CA, USA. syliao@uci.edu

ABSTRACT

Background: Transmembrane CAIX and CAXII are members of the alpha carbonic anhydrase (CA) family. They play a crucial role in differentiation, proliferation, and pH regulation. Expression of CAIX and CAXII proteins in tumor tissues is primarily induced by hypoxia and this is particularly true for CAIX, which is regulated by the transcription factor, hypoxia inducible factor-1 (HIF-1). Their distributions in normal adult human tissues are restricted to highly specialized cells that are not always hypoxic. The human fetus exists in a relatively hypoxic environment. We examined expression of CAIX, CAXII and HIF-1alpha in the developing human fetus and postnatal tissues to determine whether expression of CAIX and CAXII is exclusively regulated by HIF-1.

Results: The co-localization of CAIX and HIF-1alpha was limited to certain cell types in embryonic and early fetal tissues. Those cells comprised the primitive mesenchyma or involved chondrogenesis and skin development. Transient CAIX expression was limited to immature tissues of mesodermal origin and the skin and ependymal cells. The only tissues that persistently expressed CAIX protein were coelomic epithelium (mesothelium) and its remnants, the epithelium of the stomach and biliary tree, glands and crypt cells of duodenum and small intestine, and the cells located at those sites previously identified as harboring adult stem cells in, for example, the skin and large intestine. In many instances co-localization of CAIX and HIF-1alpha was not evident. CAXII expression is restricted to cells involved in secretion and water absorption such as parietal cells of the stomach, acinar cells of the salivary glands and pancreas, epithelium of the large intestine, and renal tubules. Co-localization of CAXII with CAIX or HIF-1alpha was not observed.

Conclusion: The study has showed that: 1) HIF-1alpha and CAIX expression co- localized in many, but not all, of the embryonic and early fetal tissues; 2) There is no evidence of co-localization of CAIX and CAXII; 3) CAIX and CAXII expression is closely related to cell origin and secretory activity involving proton transport, respectively. The intriguing finding of rare CAIX-expressing cells in those sites corresponding to stem cell niches requires further investigation.

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The embryonic period (4–8 weeks): CAIX expression was first seen in the cytotrophoblasts (A, arrow) and certain cells in the embryo (B), such as primitive mesenchyma (B1 long arrow), external surface of the embryo (B2, short double arrows), and mesenchymal cells of the chorion (B2, double long arrows). In the later embryonic stage, CAIX expression was primarily observed in the mesencyhmal cells involving chondrogenesis, as shown in the facial bone (C), bronchial tree (D), the limb (E), and the pelvic bone (F). All of the epithelial cells lining the body cavity were also positive for CAIX, e.g. the peritoneum (F), and the surface of the gonad (G). The only CAIX-positive cells in the CNS are ependymal cells (H). Original magnifications: A, B and H (20×); B1 and B2 (40×); C, D and F (4×); E and G (10×).
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Figure 1: The embryonic period (4–8 weeks): CAIX expression was first seen in the cytotrophoblasts (A, arrow) and certain cells in the embryo (B), such as primitive mesenchyma (B1 long arrow), external surface of the embryo (B2, short double arrows), and mesenchymal cells of the chorion (B2, double long arrows). In the later embryonic stage, CAIX expression was primarily observed in the mesencyhmal cells involving chondrogenesis, as shown in the facial bone (C), bronchial tree (D), the limb (E), and the pelvic bone (F). All of the epithelial cells lining the body cavity were also positive for CAIX, e.g. the peritoneum (F), and the surface of the gonad (G). The only CAIX-positive cells in the CNS are ependymal cells (H). Original magnifications: A, B and H (20×); B1 and B2 (40×); C, D and F (4×); E and G (10×).

Mentions: As early as at the 3rd to 4th week of gestation, CAIX expression was already present in the cytotrophoblasts (Fig. 1A, arrow) and rare mesenchymal cells of the chorion and the connecting stalk. In the embryo there were rare cells along the external surface (ectoderm) (Fig. 1B and 1B2, short arrows) and in the primitive mesenchyme (mesoblastic cells) that also weakly expressed CAIX (Fig. 1B1 and 1B2, long arrows). As gestation progresses, increased levels of CAIX expression were seen in the basal layer of the skin, and in the undifferentiated mesenchymal cells of the embryo involved in chondrogenesis. At 7 to 8 weeks, high levels of CAIX expression were seen in the perichondrial undifferentiated mesenchymal cells of the skeletal system, such as facial bone (Fig. 1C), the tracheobronchial cartilage (Fig. 1D), limbs and pelvic bone (Fig. 1E, 1F), and vertebrae (data not shown). All epithelial cells (mesothelial cells) and underlying mesenchyma lining the body cavities showed varying degrees of CAIX expression (Fig. 1F, 1G). As mentioned above, at the 3rd to 4th week of gestation there were only a relatively few weakly positive CAIX expressing cells identified in the embryo, and some of these cells appeared to locate near the neural plate. At 7 to 8 weeks of gestation, the only cells in the nervous system that expressed CAIX were the primitive ependymal cells, derived from the neural crest cells (Fig. 1H). It is worth noting that no other embryonic cells, besides the cells described above, expressed CAIX. For example, CAIX expression was not seen in the lung, heart (Fig. 1D), intestine (Fig. 1F), kidney or gonad (Fig. 1G).


Expression of transmembrane carbonic anhydrases, CAIX and CAXII, in human development.

Liao SY, Lerman MI, Stanbridge EJ - BMC Dev. Biol. (2009)

The embryonic period (4–8 weeks): CAIX expression was first seen in the cytotrophoblasts (A, arrow) and certain cells in the embryo (B), such as primitive mesenchyma (B1 long arrow), external surface of the embryo (B2, short double arrows), and mesenchymal cells of the chorion (B2, double long arrows). In the later embryonic stage, CAIX expression was primarily observed in the mesencyhmal cells involving chondrogenesis, as shown in the facial bone (C), bronchial tree (D), the limb (E), and the pelvic bone (F). All of the epithelial cells lining the body cavity were also positive for CAIX, e.g. the peritoneum (F), and the surface of the gonad (G). The only CAIX-positive cells in the CNS are ependymal cells (H). Original magnifications: A, B and H (20×); B1 and B2 (40×); C, D and F (4×); E and G (10×).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2666674&req=5

Figure 1: The embryonic period (4–8 weeks): CAIX expression was first seen in the cytotrophoblasts (A, arrow) and certain cells in the embryo (B), such as primitive mesenchyma (B1 long arrow), external surface of the embryo (B2, short double arrows), and mesenchymal cells of the chorion (B2, double long arrows). In the later embryonic stage, CAIX expression was primarily observed in the mesencyhmal cells involving chondrogenesis, as shown in the facial bone (C), bronchial tree (D), the limb (E), and the pelvic bone (F). All of the epithelial cells lining the body cavity were also positive for CAIX, e.g. the peritoneum (F), and the surface of the gonad (G). The only CAIX-positive cells in the CNS are ependymal cells (H). Original magnifications: A, B and H (20×); B1 and B2 (40×); C, D and F (4×); E and G (10×).
Mentions: As early as at the 3rd to 4th week of gestation, CAIX expression was already present in the cytotrophoblasts (Fig. 1A, arrow) and rare mesenchymal cells of the chorion and the connecting stalk. In the embryo there were rare cells along the external surface (ectoderm) (Fig. 1B and 1B2, short arrows) and in the primitive mesenchyme (mesoblastic cells) that also weakly expressed CAIX (Fig. 1B1 and 1B2, long arrows). As gestation progresses, increased levels of CAIX expression were seen in the basal layer of the skin, and in the undifferentiated mesenchymal cells of the embryo involved in chondrogenesis. At 7 to 8 weeks, high levels of CAIX expression were seen in the perichondrial undifferentiated mesenchymal cells of the skeletal system, such as facial bone (Fig. 1C), the tracheobronchial cartilage (Fig. 1D), limbs and pelvic bone (Fig. 1E, 1F), and vertebrae (data not shown). All epithelial cells (mesothelial cells) and underlying mesenchyma lining the body cavities showed varying degrees of CAIX expression (Fig. 1F, 1G). As mentioned above, at the 3rd to 4th week of gestation there were only a relatively few weakly positive CAIX expressing cells identified in the embryo, and some of these cells appeared to locate near the neural plate. At 7 to 8 weeks of gestation, the only cells in the nervous system that expressed CAIX were the primitive ependymal cells, derived from the neural crest cells (Fig. 1H). It is worth noting that no other embryonic cells, besides the cells described above, expressed CAIX. For example, CAIX expression was not seen in the lung, heart (Fig. 1D), intestine (Fig. 1F), kidney or gonad (Fig. 1G).

Bottom Line: Co-localization of CAXII with CAIX or HIF-1alpha was not observed.The study has showed that: 1) HIF-1alpha and CAIX expression co- localized in many, but not all, of the embryonic and early fetal tissues; 2) There is no evidence of co-localization of CAIX and CAXII; 3) CAIX and CAXII expression is closely related to cell origin and secretory activity involving proton transport, respectively.The intriguing finding of rare CAIX-expressing cells in those sites corresponding to stem cell niches requires further investigation.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pathology, St. Joseph Hospital, Orange, CA, USA. syliao@uci.edu

ABSTRACT

Background: Transmembrane CAIX and CAXII are members of the alpha carbonic anhydrase (CA) family. They play a crucial role in differentiation, proliferation, and pH regulation. Expression of CAIX and CAXII proteins in tumor tissues is primarily induced by hypoxia and this is particularly true for CAIX, which is regulated by the transcription factor, hypoxia inducible factor-1 (HIF-1). Their distributions in normal adult human tissues are restricted to highly specialized cells that are not always hypoxic. The human fetus exists in a relatively hypoxic environment. We examined expression of CAIX, CAXII and HIF-1alpha in the developing human fetus and postnatal tissues to determine whether expression of CAIX and CAXII is exclusively regulated by HIF-1.

Results: The co-localization of CAIX and HIF-1alpha was limited to certain cell types in embryonic and early fetal tissues. Those cells comprised the primitive mesenchyma or involved chondrogenesis and skin development. Transient CAIX expression was limited to immature tissues of mesodermal origin and the skin and ependymal cells. The only tissues that persistently expressed CAIX protein were coelomic epithelium (mesothelium) and its remnants, the epithelium of the stomach and biliary tree, glands and crypt cells of duodenum and small intestine, and the cells located at those sites previously identified as harboring adult stem cells in, for example, the skin and large intestine. In many instances co-localization of CAIX and HIF-1alpha was not evident. CAXII expression is restricted to cells involved in secretion and water absorption such as parietal cells of the stomach, acinar cells of the salivary glands and pancreas, epithelium of the large intestine, and renal tubules. Co-localization of CAXII with CAIX or HIF-1alpha was not observed.

Conclusion: The study has showed that: 1) HIF-1alpha and CAIX expression co- localized in many, but not all, of the embryonic and early fetal tissues; 2) There is no evidence of co-localization of CAIX and CAXII; 3) CAIX and CAXII expression is closely related to cell origin and secretory activity involving proton transport, respectively. The intriguing finding of rare CAIX-expressing cells in those sites corresponding to stem cell niches requires further investigation.

Show MeSH
Related in: MedlinePlus