Differential regulation of specification and subsequent migration of neural crest progenitors

• Applicant: Professor Dr. Klaus Unsicker
• Co-Applicant: Professorin Chaya Kalcheim, Ph.D.
• Subject Area: Molecular Biology and Physiology of Neurons and Glial Cells
• Term: from 2012 to 2016
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 209911085

• Final Report Year: 2016

Final Report Abstract

The main goal of this proposal was to shed light on the relationship between cell specification and migration. To this end, we focused on two main developmental choices. The neural-melanocyte switch and the NC-roof plate switch. We found that the melanocyte lineage segregates from the neural lineages of the NC earlier than previously reported and that this segregation is associated with the expression of the appropriate guidance molecules that take the cells through their normal journey towards their homing sites. We defined the role of the transcription factor Foxd3 as well as that of Snail2 and Sox9 as crucial players in the specification/guidance choice. We found that this holds true both for melanocytes derived directly from late- emigrating NC (epaxial) as well as for the Schwann cell progenitor-derived melanocytes. Additionally, although specification and guidance are intimately linked during normal ontogeny, these processes can be experimentally uncoupled. Finally, we demonstrated that distinct levels of BMP signaling (and/or various durations of the signal) are not only essential for NC delamination but also for the transition from a migratory NC (PNS) to a roof plate phase (CNS) of neural tube development.

Publications

• (2013) A dynamic code of dorsal neural tube genes regulates the segregation between neurogenic and melanogenic neural crest cells. Development, 140, 2269-79
  Nitzan, E; Krispin, S; Pfaltzgraff, E; Klar, A; Labosky, P and Kalcheim, C.
  
• (2013) Neural crest and somitic mesoderm as paradigms to investigate cell fate decisions during development. Dev. Growth Differ. 55, 60-78
  Nitzan, E. and Kalcheim, C.
  
• (2013). Neural crest and Schwann cell progenitor-derived melanocytes constitute two spatially segregated populations similarly regulated by Foxd3. Proc. Natl. Acad. Sci. USA, 110,12709-14
  Nitzan, E., Pfaltzgraff, E.R., Labosky, P.R., and Kalcheim, C.
  
• (2013). Resolved and open issues in chromaffin cell development. Mech. Devel. 130, 324-329
  Unsicker, K., Huber, K., Schober, A., and Kalcheim, C.
  
• (2013). Sympathetic neurons and chromaffin cells share a common progenitor in the neural crest in vivo. Neural Development, 8:12
  Shtukmaster, S., Schier. M., Huber, K., Krispin, S., Kalcheim, C. and Unsicker, K.
  
• Epithelial-Mesenchymal transitions during Neural Crest and Somite development. J. Clin. Med, 2015 Dec 25;5(1)
  Kalcheim, C.
  
• (2016) Dynamics of BMP and Hes1/Hairy1 signaling in the dorsal neural tube underlies the transition from Neural Crest to definitive Roof Plate. BMC Biology, 14:23
  Nitzan, E.; Avraham, O., Kahane, N., Ofek, S., Kumar, D., and Kalcheim, C.
  
• MiR-124 is differentially expressed in derivatives of the sympathoadrenal cell lineage and promotes neurite elongation in chromaffin cells. Cell Tiss. Res. 2016 April 19 (Epub ahead of print)
  Shtukmaster, S., Narasimhan, P., El Taiwri, T., Stubbusch, J., Enrsberger, U., Rohrer, H., Unsicker, K., Huber, K.