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In Vivo Expression of the PTB-deleted Odin Mutant Results in Hydrocephalus.

Park S, Lee H, Park S - Mol. Cells (2015)

Bottom Line: Interestingly, we found that Odin was exclusively expressed in ependymal cells along the brain ventricles.In addition, Odin-dPTB expression disrupted proper development of the subcommissural organ and interfered with ependymal cell maturation in the cerebral aqueduct.Taken together, our findings strongly suggest that Odin plays a role in the differentiation of ependymal cells during early postnatal brain development.

View Article: PubMed Central - PubMed

Affiliation: Department of Biological Science, Sookmyung Women's University, Seoul 140-742, Korea.

ABSTRACT
Odin has been implicated in the downstream signaling pathway of receptor tyrosine kinases, such as the epidermal growth factor and Eph receptors. However, the physiologically relevant function of Odin needs to be further determined. In this study, we used Odin heterozygous mice to analyze the Odin expression pattern; the targeted allele contained a β-geo gene trap vector inserted into the 14th intron of the Odin gene. Interestingly, we found that Odin was exclusively expressed in ependymal cells along the brain ventricles. In particular, Odin was highly expressed in the subcommissural organ, a small ependymal glandular tissue. However, we did not observe any morphological abnormalities in the brain ventricles or ependymal cells of Odin -mutant mice. We also generated BAC transgenic mice that expressed the PTB-deleted Odin (dPTB) after a floxed GFP-STOP cassette was excised by tissue-specific Cre expression. Strikingly, Odin-dPTB expression played a causative role in the development of the hydrocephalic phenotype, primarily in the midbrain. In addition, Odin-dPTB expression disrupted proper development of the subcommissural organ and interfered with ependymal cell maturation in the cerebral aqueduct. Taken together, our findings strongly suggest that Odin plays a role in the differentiation of ependymal cells during early postnatal brain development.

No MeSH data available.


Related in: MedlinePlus

The midbrain of Odin-dPTB mice becomes severely expanded upon Cre expression. (A and D) The coronal sections of the indicated brains were analyzed by cresyl violet staining. Note that both the cerebral aqueduct and inferior colliculus (ic) are severely expanded. ME, medulla. (B and E) Enlarged view of the cerebral aqueduct regions in A and D, respectively. (C and F) High magnification of the ependymal cells lining the cerebral aqueduct in B and E. Note that the ependymal cells of control mice have a regular and well organized morphology, whereas those of the double transgenic mice do not.
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f4-molce-38-5-426: The midbrain of Odin-dPTB mice becomes severely expanded upon Cre expression. (A and D) The coronal sections of the indicated brains were analyzed by cresyl violet staining. Note that both the cerebral aqueduct and inferior colliculus (ic) are severely expanded. ME, medulla. (B and E) Enlarged view of the cerebral aqueduct regions in A and D, respectively. (C and F) High magnification of the ependymal cells lining the cerebral aqueduct in B and E. Note that the ependymal cells of control mice have a regular and well organized morphology, whereas those of the double transgenic mice do not.

Mentions: The SCO is located in a dorsocaudal region of the third ventricle, at the entrance of the cerebral aqueduct (Rodriguez et al., 1998). Therefore, malformation of the SCO may have a causative role in the severe midbrain hydrocephalic phenotype (Picketts, 2006). We further examined the anatomical structure of the midbrain in the double transgenic lines. Consistent with the hydrocephalic morphology of the whole brain, the midbrain and cerebral aqueduct were severely enlarged in double transgenic mice (Figs. 4A, 4B, 4D, and 4E). In contrast, the sizes of the cerebellum and medulla were not significantly altered in double transgenic mice. In addition, neither apoptotic cells nor proliferative (pH3-positive) cells increased significantly in the midbrain region (data not shown). Importantly, ependymal cells of control mice appeared to be well organized with epithelial-like morphology, whereas those of double transgenic mice looked irregular and disorganized (Figs. 4C and 4F). To further investigate whether ependymal cells lining the cerebral aqueduct were properly differentiated in double transgenic mice, we performed acetylated tubulin antibody staining on midbrain sagittal sections. As we predicted, the ependymal cells lining the cerebral aqueduct of double transgenic mice were mostly negative for acetylated tubulin antibody staining (Figs. 5A–5J). This result strongly suggests that ependymal cells in the midbrain are defective for proper development of multi-cilia. Taken together, these findings support our hypothesis that Odin plays a role in the development of ependymal cells in the diencephalon and mesencephalon during early postnatal brain development.


In Vivo Expression of the PTB-deleted Odin Mutant Results in Hydrocephalus.

Park S, Lee H, Park S - Mol. Cells (2015)

The midbrain of Odin-dPTB mice becomes severely expanded upon Cre expression. (A and D) The coronal sections of the indicated brains were analyzed by cresyl violet staining. Note that both the cerebral aqueduct and inferior colliculus (ic) are severely expanded. ME, medulla. (B and E) Enlarged view of the cerebral aqueduct regions in A and D, respectively. (C and F) High magnification of the ependymal cells lining the cerebral aqueduct in B and E. Note that the ependymal cells of control mice have a regular and well organized morphology, whereas those of the double transgenic mice do not.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4443284&req=5

f4-molce-38-5-426: The midbrain of Odin-dPTB mice becomes severely expanded upon Cre expression. (A and D) The coronal sections of the indicated brains were analyzed by cresyl violet staining. Note that both the cerebral aqueduct and inferior colliculus (ic) are severely expanded. ME, medulla. (B and E) Enlarged view of the cerebral aqueduct regions in A and D, respectively. (C and F) High magnification of the ependymal cells lining the cerebral aqueduct in B and E. Note that the ependymal cells of control mice have a regular and well organized morphology, whereas those of the double transgenic mice do not.
Mentions: The SCO is located in a dorsocaudal region of the third ventricle, at the entrance of the cerebral aqueduct (Rodriguez et al., 1998). Therefore, malformation of the SCO may have a causative role in the severe midbrain hydrocephalic phenotype (Picketts, 2006). We further examined the anatomical structure of the midbrain in the double transgenic lines. Consistent with the hydrocephalic morphology of the whole brain, the midbrain and cerebral aqueduct were severely enlarged in double transgenic mice (Figs. 4A, 4B, 4D, and 4E). In contrast, the sizes of the cerebellum and medulla were not significantly altered in double transgenic mice. In addition, neither apoptotic cells nor proliferative (pH3-positive) cells increased significantly in the midbrain region (data not shown). Importantly, ependymal cells of control mice appeared to be well organized with epithelial-like morphology, whereas those of double transgenic mice looked irregular and disorganized (Figs. 4C and 4F). To further investigate whether ependymal cells lining the cerebral aqueduct were properly differentiated in double transgenic mice, we performed acetylated tubulin antibody staining on midbrain sagittal sections. As we predicted, the ependymal cells lining the cerebral aqueduct of double transgenic mice were mostly negative for acetylated tubulin antibody staining (Figs. 5A–5J). This result strongly suggests that ependymal cells in the midbrain are defective for proper development of multi-cilia. Taken together, these findings support our hypothesis that Odin plays a role in the development of ependymal cells in the diencephalon and mesencephalon during early postnatal brain development.

Bottom Line: Interestingly, we found that Odin was exclusively expressed in ependymal cells along the brain ventricles.In addition, Odin-dPTB expression disrupted proper development of the subcommissural organ and interfered with ependymal cell maturation in the cerebral aqueduct.Taken together, our findings strongly suggest that Odin plays a role in the differentiation of ependymal cells during early postnatal brain development.

View Article: PubMed Central - PubMed

Affiliation: Department of Biological Science, Sookmyung Women's University, Seoul 140-742, Korea.

ABSTRACT
Odin has been implicated in the downstream signaling pathway of receptor tyrosine kinases, such as the epidermal growth factor and Eph receptors. However, the physiologically relevant function of Odin needs to be further determined. In this study, we used Odin heterozygous mice to analyze the Odin expression pattern; the targeted allele contained a β-geo gene trap vector inserted into the 14th intron of the Odin gene. Interestingly, we found that Odin was exclusively expressed in ependymal cells along the brain ventricles. In particular, Odin was highly expressed in the subcommissural organ, a small ependymal glandular tissue. However, we did not observe any morphological abnormalities in the brain ventricles or ependymal cells of Odin -mutant mice. We also generated BAC transgenic mice that expressed the PTB-deleted Odin (dPTB) after a floxed GFP-STOP cassette was excised by tissue-specific Cre expression. Strikingly, Odin-dPTB expression played a causative role in the development of the hydrocephalic phenotype, primarily in the midbrain. In addition, Odin-dPTB expression disrupted proper development of the subcommissural organ and interfered with ependymal cell maturation in the cerebral aqueduct. Taken together, our findings strongly suggest that Odin plays a role in the differentiation of ependymal cells during early postnatal brain development.

No MeSH data available.


Related in: MedlinePlus