title: A new role of hindbrain boundaries as pools of neural stem/progenitor cells regulated by Sox2.
abstract: Compartment boundaries are an essential developmental mechanism throughout evolution, designated to act as organizing centers and to regulate and localize differently fated cells. The hindbrain serves as a fascinating example for this phenomenon as its early development is devoted to the formation of repetitive rhombomeres and their well-defined boundaries in all vertebrates. Yet, the actual role of hindbrain boundaries remains unresolved, especially in amniotes.
  
  
  
  Here, we report that hindbrain boundaries in the chick embryo consist of a subset of cells expressing the key neural stem cell (NSC) gene Sox2. These cells co-express other neural progenitor markers such as Transitin (the avian Nestin), GFAP, Pax6 and chondroitin sulfate proteoglycan. The majority of the Sox2(+) cells that reside within the boundary core are slow-dividing, whereas nearer to and within rhombomeres Sox2(+) cells are largely proliferating. In vivo analyses and cell tracing experiments revealed the contribution of boundary Sox2(+) cells to neurons in a ventricular-to-mantle manner within the boundaries, as well as their lateral contribution to proliferating Sox2(+) cells in rhombomeres. The generation of boundary-derived neurospheres from hindbrain cultures confirmed the typical NSC behavior of boundary cells as a multipotent and self-renewing Sox2(+) cell population. Inhibition of Sox2 in boundaries led to enhanced and aberrant neural differentiation together with inhibition in cell-proliferation, whereas Sox2 mis-expression attenuated neurogenesis, confirming its significant function in hindbrain neuronal organization.
  
  
  
  Data obtained in this study deciphers a novel role of hindbrain boundaries as repetitive pools of neural stem/progenitor cells, which provide proliferating progenitors and differentiating neurons in a Sox2-dependent regulation.
authors.affiliation: Koret School of Veterinary Medicine, The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot, 76100, Israel.
authors.forename: Yuval
authors.initials: Y
authors.lastname: Peretz
authors.affiliation: Koret School of Veterinary Medicine, The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot, 76100, Israel.
authors.forename: Noa
authors.initials: N
authors.lastname: Eren
authors.affiliation: Koret School of Veterinary Medicine, The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot, 76100, Israel.
authors.forename: Ayelet
authors.initials: A
authors.lastname: Kohl
authors.affiliation: Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Gideon
authors.initials: G
authors.lastname: Hen
authors.affiliation: Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Karina
authors.initials: K
authors.lastname: Yaniv
authors.affiliation: Department of Stem Cell and Regenerative Biology, Harvard Stem Cell Institute, Harvard University, Cambridge, MA, USA.
authors.forename: Karen
authors.initials: K
authors.lastname: Weisinger
authors.affiliation: Institute of Animal Sciences, Department of Poultry and Aquaculture Sciences, Agricultural Research Organization, The Volcani Center, Bet Dagan, Israel.
authors.forename: Yuval
authors.initials: Y
authors.lastname: Cinnamon
authors.affiliation: Koret School of Veterinary Medicine, The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot, 76100, Israel. dalit.seladon@mail.huji.ac.il.
authors.forename: Dalit
authors.identifier: 0000-0001-7498-061X
authors.initials: D
authors.lastname: Sela-Donenfeld
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D019521:Body Patterning; D002454:Cell Differentiation; D002465:Cell Movement; D049109:Cell Proliferation; D000066673:Cell Self Renewal; D002642:Chick Embryo; D008954:Models, Biological; D058953:Neural Stem Cells / Q000166:cytology* / Q000378:metabolism; D012249:Rhombencephalon / Q000166:cytology* / Q000196:embryology; D055748:SOXB1 Transcription Factors / Q000378:metabolism*; D018874:Spheroids, Cellular / Q000166:cytology; D013997:Time Factors
chemical_list: D015415:Biomarkers; D055748:SOXB1 Transcription Factors
keywords: Hindbrain boundaries; Neural differentiation; Neural stem/progenitors; Rhombomere; Sox2