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. 2015 Apr 8;9:119. doi: 10.3389/fncel.2015.00119

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Copyright © 2015 Yap and Winckler.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution and reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Roles of numb in polarizing signaling responses downstream of BDNF in migrating granule cell precursors (GCPs) in cerebellar development. Polarized distribution of numb at the leading process of a migrating GCP creates a positive feed-forward loop for directional migration. The following steps are proposed (based on Zhou et al., 2011). (1) Higher BDNF in front of migrating GCP. (2) Higher activation of TrkB. (3) Higher recruitment of numb. (4) Higher recruitment of downstream effectors, such as aPKC. (5) Higher numb leads to higher TrkB-P endocytosis via clathrin/AP-2. (6) Higher TrkB endocytosis leads to more TrkB-P in endosomes. (7) More TrkB-P in endosomes recruits more signaling effectors to endosomes. (8) Higher activation of Tiam and Rac to promote more actin assembly in front of cell. (9) Higher signaling promotes preferential recycling of TrkB back to surface at front. (10) TrkB distribution becomes more polarized near front.