Study on the role of DLK1 on neurogenic cell differentiation.
| Autor: | Ching-Yu Lai, 賴靜玉 |
|---|---|
| Rok vydání: | 2008 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 96 Delta-like 1 Homologue (Dlk1) is a transmembranous protein of 383 amino acids, belonging to the epidermal growth factor-like homeotic superfamily that includes Notch, Delta and Serrate. Dlk1 is known to participate in several differentiation processes. It was initially found to function as a negative regulator of adipocyte differentiation. It was lately reported to be able to inhibit differentiation of hematopoietic cells, osteoblasts, and colonic epithelial cells and to overexpress in transit amplification of oval cells in the liver. Its role in differentiation, therefore, is most likely a negative regulator. Dlk1 has also been reported to be involved in differentiation and growth arrest of the peripheral and central nervous system. It is currently known that Dlk1 is highly expressed in the neuroendocrine tumors such as pheochromocytomas and neuroblastomas, whereas the exact stage that Dlk1 is involved in the neurogenic cell differentiation is still unclear. Immature teratoma is composed of variable amounts of immature embryonal-type tissue mostly including neuroepithelial component admixed with mature tissue, and neuroblastoma (NB), ganglioneuroblastoma (GNB) and ganglioneuroma (GN) are a spectrum of tumors with various degrees of neuroblastic differentiation and maturation. To investigate the expression of Dlk1 during neurogenic cell differentiation, we selected both immature teratoma containing neuroepithelial component and NB/GNB/GN as models to study the distribution of Dlk1 comparing with other stem cell and neurogenic differentiation markers including Oct4, Nestin, CD56 (N-CAM), GFAP, synaptophysin and neurofilaments by immunohistochemistry on tissue microarray, and performed in situ hybridization for the distribution of Dlk1 mRNA on the paraffin-embedded tissue of both immature teratoma and NB/GNB/GN. The results showed that there was moderate Dlk1 expression in the cells around the neural tube structures in the immature teratomas, whereas the expression became weakened in the differentiated neuroepithelial cells. In the mature brain-like glial tissue, Dlk1 expression was much weaker or undetectable. In addition, Dlk1 was detected in the undifferentiated neuroblasts, and was still present in the differentiating neuroblasts and immature ganglion cells in the NB and GNB. In GN, variable Dlk1 expression was found in the ganglion cells, but not in the Schwann-like cells. The expression of Dlk1 mRNA detected by in situ hybridization was compatible with that of the Dlk1 protein detected by immunohistochemistry. This study demonstrated that during neuroepithelial cell differentiation Dlk1 was mainly expressed in the early stage and the expression was decreased in the late stage. To further investigate the functional role of Dlk1 on neuroepithelial differentiation, we will knock down Dlk1 by siRNA on neuroblastoma cell line to study the influences of Dlk1 on cell phenotype and differentiation. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
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