TY - JOUR
T1 - Brief Report
T2 - Robo1 Regulates the Migration of Human Subventricular Zone Neural Progenitor Cells During Development
AU - Guerrero-Cazares, Hugo
AU - Lavell, Emily
AU - Chen, Linda
AU - Schiapparelli, Paula
AU - Lara-Velazquez, Montserrat
AU - Capilla-Gonzalez, Vivian
AU - Clements, Anna Christina
AU - Drummond, Gabrielle
AU - Noiman, Liron
AU - Thaler, Katrina
AU - Burke, Anne
AU - Quiñones-Hinojosa, Alfredo
N1 - Funding Information:
We thank Sural Ranamukhaarachchi, Raisa Rauf, and Matt Sklar for their help in this work and Dr. Oscar Gonzalez-Perez for his critical comments. H.G.C., A.Q.H., V.C.G., and P.S. were supported by the National Institutes of Health (R01NS070024); H.G.C. and E.L. were supported by the National Cancer Institute (R21CA199295) and the Maryland Stem Cells Research Fund; L.C. was supported by the Howard Hughes Medical Institute; V.C.G. was supported by the Fundacion Progreso y Salud of the Andalusian Regional Ministry of Health (PI01092014).
Publisher Copyright:
© 2017 AlphaMed Press
PY - 2017/7
Y1 - 2017/7
N2 - Human neural progenitor cell (NPC) migration within the subventricular zone (SVZ) of the lateral ganglionic eminence is an active process throughout early brain development. The migration of human NPCs from the SVZ to the olfactory bulb during fetal stages resembles what occurs in adult rodents. As the human brain develops during infancy, this migratory stream is drastically reduced in cell number and becomes barely evident in adults. The mechanisms regulating human NPC migration are unknown. The Slit–Robo signaling pathway has been defined as a chemorepulsive cue involved in axon guidance and neuroblast migration in rodents. Slit and Robo proteins expressed in the rodent brain help guide neuroblast migration from the SVZ through the rostral migratory stream to the olfactory bulb. Here, we present the first study on the role that Slit and Robo proteins play in human-derived fetal neural progenitor cell migration (hfNPC). We describe that Robo1 and Robo2 isoforms are expressed in the human fetal SVZ. Furthermore, we demonstrate that Slit2 is able to induce a chemorepellent effect on the migration of hfNPCs derived from the human fetal SVZ. In addition, when Robo1 expression is inhibited, hfNPCs are unable to migrate to the olfactory bulb of mice when injected in the anterior SVZ. Our findings indicate that the migration of human NPCs from the SVZ is partially regulated by the Slit–Robo axis. This pathway could be regulated to direct the migration of NPCs in human endogenous neural cell therapy. Stem Cells 2017;35:1860–1865.
AB - Human neural progenitor cell (NPC) migration within the subventricular zone (SVZ) of the lateral ganglionic eminence is an active process throughout early brain development. The migration of human NPCs from the SVZ to the olfactory bulb during fetal stages resembles what occurs in adult rodents. As the human brain develops during infancy, this migratory stream is drastically reduced in cell number and becomes barely evident in adults. The mechanisms regulating human NPC migration are unknown. The Slit–Robo signaling pathway has been defined as a chemorepulsive cue involved in axon guidance and neuroblast migration in rodents. Slit and Robo proteins expressed in the rodent brain help guide neuroblast migration from the SVZ through the rostral migratory stream to the olfactory bulb. Here, we present the first study on the role that Slit and Robo proteins play in human-derived fetal neural progenitor cell migration (hfNPC). We describe that Robo1 and Robo2 isoforms are expressed in the human fetal SVZ. Furthermore, we demonstrate that Slit2 is able to induce a chemorepellent effect on the migration of hfNPCs derived from the human fetal SVZ. In addition, when Robo1 expression is inhibited, hfNPCs are unable to migrate to the olfactory bulb of mice when injected in the anterior SVZ. Our findings indicate that the migration of human NPCs from the SVZ is partially regulated by the Slit–Robo axis. This pathway could be regulated to direct the migration of NPCs in human endogenous neural cell therapy. Stem Cells 2017;35:1860–1865.
KW - Cell migration
KW - Human subventricular zone
KW - Neural stem cells
KW - Slit2
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UR - http://www.scopus.com/inward/citedby.url?scp=85018884678&partnerID=8YFLogxK
U2 - 10.1002/stem.2628
DO - 10.1002/stem.2628
M3 - Article
C2 - 28406573
AN - SCOPUS:85018884678
SN - 1066-5099
VL - 35
SP - 1860
EP - 1865
JO - Stem Cells
JF - Stem Cells
IS - 7
ER -