DOI QR코드

DOI QR Code

Wnt signaling이 neural crest lineage segregation과 specification에 미치는 영향

The Effects of Wnt Signaling on Neural Crest Lineage Segregation and Specification

  • 송진수 (원광대학교 자연과학대학 생명과학학부) ;
  • 진은정 (원광대학교 자연과학대학 생명과학학부)
  • Song, Jin-Su (Department of Biological Sciences, College of Natural Sciences and Institute of Biotechnology, Wonkwang University) ;
  • Jin, Eun-Jung (Department of Biological Sciences, College of Natural Sciences and Institute of Biotechnology, Wonkwang University)
  • 발행 : 2009.10.30

초록

Neural crest는 신경계의 발생과정에서 생긴 특정화된 외배엽으로서 말초신경계(peripheral nervous system)의 모든 sensory cells과 peripheral cells, unipolar spinal ganglion cell, cranial sensory ganglia, peripheral nerve의 neurolemmal sheath cells, ganglia의 capsule cells, sympathetic ganglia, chromaffin cells, pigment cell 등의 자율신 경계의 대부분의 세포로 분화 한다. 최근pluripotetic neural crest cells의 운명이 이미 제한되어 있으며, 이러한 fate-restricted crest cells이 neural tube에서 emigration된다고 보고된바 있다. 또한 본 연구자는 Wnt와 Wnt의 antagonist가 neural crest cell의 specification이 일어나는 시기에 발현하여, neural crest cell의 segregation과 differentiation에 직접적으로 관여함을 밝혔다. 이를 보다 명확히 규명하기 위해, 본 연구에서는 neural tube에 Wnt-3a expressing cell의 grafting 혹은 dominant negative GSK construct의 electroporation을 통해 Wnt signaling을 modulation 하여 downstream mediator를 조사하였다. Wnt signaling의 stimulation은 neural crest cell의 melanoblast 로의 commitment를 유도하였으며, 이와 더불어 cadherin 7과 slug의 발현을 조절함을 확인하였다.

Recent evidence has shown that many pluripotetic neural crest cells are fate-restricted and that different fate-restricted crest cells emigrate from the neural tube at different times. Jin et al. (2001) identified the expression patterns of Wnts and its antagonists at the time that neural crest cells were being specified and suggested that Wnt signaling was involved in the segregation/differentiation of neural crest cells in the trunk in vitro. In this study, we evaluated the effects of Wnt signaling in avian neural crest lineage segregation. To accomplish this, Wnt signaling was disturbed at the time of neural crest segregation and differentiation by grafting Wnt-3a expressing cells and conducting dominant negative glycogen synthase kinase (dnGSK) electroporation. Stimulation of Wnt signaling induced neural crest lineage segregation and melanoblast specification, and increased the expression levels of genes known to be involved in neural crest development such as cadherin 7 and Slug, which suggests that they are involved in Wnt-induced neural crest lineage differentiation into melanoblasts.

키워드

참고문헌

  1. Barrio, M. G. and A. Nieto. 2002. Overexpression of Snail family members highlights their ability to promote chick neural crest formation. Development 129, 1583-1593
  2. Bienz, M. 1998. TCF: transcriptional activator or repressor? Curro Opin. Cell BioI. 10, 366-372 https://doi.org/10.1016/S0955-0674(98)80013-6
  3. Bradley, R S., P. Cowin, and A. M. Brown. 1993. Expression of Wnt-1 in PC12 cells results in modulation of plakoglobin and E-cadherin and increased cellular adhesion. J. Cell BioI. 123, 1857-1865 https://doi.org/10.1083/jcb.123.6.1857
  4. Chapman, S. c., J. Collignon, G. Schownwolf, and A. Lumsden. 2001. Improved method for chick whole-embryo culture using a filter paper carrier. Dev. Dyn. 220, 284-289 https://doi.org/10.1002/1097-0177(20010301)220:3<284::AID-DVDY1102>3.0.CO;2-5
  5. Clevers, H. and M. Van De Watering. 1997. TCF/LEF factors earn their wings. Trends Genet. 13, 485-489
  6. Garcia-Castro, M. I., C. Marcelle, and M. Bronner-Fraser. 2002. Ectodermal Wnt function as a neural crest inducer. Science 297, 848-851
  7. Goulding, M. D., A. Lumsden, and P. Gruss. 1993. Signals from the notochord and floor plate regulate the region-specific expression of two Pax genes in the developing spinal cord. Development 117, 1001-1016
  8. Hamburger, V. and H. 1. Hamilton. 1951. A series of normal stages in the development of the chick embryo. J. Morphol. 88, 49-92 https://doi.org/10.1002/jmor.1050880104
  9. Henion, P. D. and J. A. Weston. 1997. Timing and pattern of cell fate restrictions in the neural crest lineage. Development 124, 4351-4359
  10. Hinck, 1., W. J. Nelson, and J. Papkoff. 1994. Wnt-1 modulates cell-cell adhesion in mammalian cells by stabilizing ~catenin binding to the cell adhesion protein cadherin. J. Cell BioI. 124, 729-741 https://doi.org/10.1083/jcb.124.5.729
  11. Hollyday, M., J. A. McMahon, and A. P. McMahon. 1995. Wnt expression patterns in chick embryo nervous system. Mech. Dev. 52, 9-25 https://doi.org/10.1016/0925-4773(95)00385-E
  12. Jin, E-J., C. A. Erickson, S. Takada, and 1. W. Burrus. 2001. Wnt and BMP signaling govern lineage segregation of melanocytes in the avian embryo. Dev. BioI. 233, 22-37 https://doi.org/10.1006/dbio.2001.0222
  13. Kos R, M. V. Reedy, R 1. Johnson, and C. A Erickson. 2001. The winged-helix transcription factor FoxD3 is important for establishing the neural crest lineage and repressing melanogenesis in avian embryos. Development 128, 1467-1479
  14. Nakagawa, S. and M. Takeichi. 1995. Neural crest cell-cell adhesion controlled by sequential and subpopulation-specific expression of novel cadherins. Development 121, 1321-1332 https://doi.org/10.1126/science.2762814
  15. Nakagawa, S. and M. Takeichi. 1998. Neural crest emigration from the neural tube depends on regulated cadherin expression. Development 125, 2963-2971
  16. Nieto, M. A, M. G. Sargent, D. G. Wilkinson, and J. Cooke. 1994. Control of cell behaviour during vertebrate development by Slug, a zinc finger gene. Science 264, 835-839 https://doi.org/10.1126/science.7513443
  17. Nusse, R 1997. A versatile transcriptional effector of Wingless signaling. Cell 6, 1302-1306
  18. Papkoff, J., B. Rubinfeld, B. Schryver, and P. Polakis. 1996. Wnt-1 regulates free pools of catenins and stabilizers APC-catenin complexes. Mol. Cell BioI. 16, 2128-2134
  19. Reedy, M. V., C. D. Faraco, and C. A Erickson. 1998. The delayed entry of thoracic neural crest cells into the dorsolateral path is a consequence of the late emigration of melanogenic neural crest cells from the neural tube. Dev. BioI. 200, 234-246 https://doi.org/10.1006/dbio.1998.8963
  20. Roelink, H. and R Nusse. 1991. Expression of two members of the Wnt family during mouse development-restricted temporal and spatial patterns in the developing neural tube. Genes Dev. 5, 381-388 https://doi.org/10.1101/gad.5.3.381
  21. Takada, K, K Yaumoto, R Takada, S. Takada, K Watanabe, T. Udono, H. Saito, K Takahashi, and S. Shibahara. 2000. Induction of melanocyte-specific microphthalmia-associated transcription factor by Wnt-3a. J. BioI. Chem. 275, 14012-14016
  22. Trainor, P. and R Krumlauf. 2002. Develpoment. Riding the crest of the Wnt signaling wave. Science 297, 781-783 https://doi.org/10.1126/science.1075454
  23. Wilkinson, D. G., J. A. Bailes, and A. P. McMahon. 1987. Expression of the proto-oncogene int-1 is restricted to specific neural cells in the developing mouse embryo. Cell 50, 79-88 https://doi.org/10.1016/0092-8674(87)90664-7