scholarly journals 14-3-3 Proteins Regulate a Cell-Intrinsic Switch from Sonic Hedgehog-Mediated Commissural Axon Attraction to Repulsion after Midline Crossing

Neuron ◽  
2012 ◽  
Vol 76 (4) ◽  
pp. 735-749 ◽  
Author(s):  
Patricia T. Yam ◽  
Christopher B. Kent ◽  
Steves Morin ◽  
W. Todd Farmer ◽  
Ricardo Alchini ◽  
...  
eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Keisuke Onishi ◽  
Yimin Zou

Commissural axons switch on responsiveness to Wnt attraction during midline crossing and turn anteriorly only after exiting the floor plate. We report here that Sonic Hedgehog (Shh)-Smoothened signaling downregulates Shisa2, which inhibits the glycosylation and cell surface presentation of Frizzled3 in rodent commissural axon growth cones. Constitutive Shisa2 expression causes randomized turning of post-crossing commissural axons along the anterior–posterior (A–P) axis. Loss of Shisa2 led to precocious anterior turning of commissural axons before or during midline crossing. Post-crossing commissural axon turning is completely randomized along the A–P axis when Wntless, which is essential for Wnt secretion, is conditionally knocked out in the floor plate. This regulatory link between Shh and planar cell polarity (PCP) signaling may also occur in other developmental processes.


2007 ◽  
Vol 301 (1) ◽  
pp. 166-177 ◽  
Author(s):  
Elena Simionato ◽  
Natalia Barrios ◽  
Louise Duloquin ◽  
Elisabeth Boissonneau ◽  
Pierrette Lecorre ◽  
...  

2008 ◽  
Vol 294 (4) ◽  
pp. G844-G849 ◽  
Author(s):  
Shohreh F. Farzan ◽  
Samer Singh ◽  
Neal S. Schilling ◽  
David J. Robbins

The Hedgehog (Hh) family of secreted proteins is necessary for aspects of the development and maintenance of the gastrointestinal tract. Hh is thought to function as a morphogen, a mitogen, a cell survival factor, and an axon guidance factor. Given its wide role in development, as well as in a variety of disease states, understanding the regulation of Hh function and activity is critically important. However, the study of Hh signaling has been impeded by its unusual biology. Hh is unique in that it is the only protein covalently modified by cholesterol, which in turn affects numerous aspects of its localization, release, movement, and activity. All are important factors when considering Hh's physiological role, and animals have developed an intricate system of regulators responsible for both promoting and inhibiting the activity of Hh. This review is intended to give a broad overview of how the biosynthesis and movement of Hh contributes to its biological activity.


2015 ◽  
Vol 29 (24) ◽  
pp. 2617-2632
Author(s):  
Berenice Hernandez-Enriquez ◽  
Zhuhao Wu ◽  
Edward Martinez ◽  
Olav Olsen ◽  
Zaven Kaprielian ◽  
...  

Commissural axon guidance depends on a myriad of cues expressed by intermediate targets. Secreted semaphorins signal through neuropilin-2/plexin-A1 receptor complexes on post-crossing commissural axons to mediate floor plate repulsion in the mouse spinal cord. Here, we show that neuropilin-2/plexin-A1 are also coexpressed on commissural axons prior to midline crossing and can mediate precrossing semaphorin-induced repulsion in vitro. How premature semaphorin-induced repulsion of precrossing axons is suppressed in vivo is not known. We discovered that a novel source of floor plate-derived, but not axon-derived, neuropilin-2 is required for precrossing axon pathfinding. Floor plate-specific deletion of neuropilin-2 significantly reduces the presence of precrossing axons in the ventral spinal cord, which can be rescued by inhibiting plexin-A1 signaling in vivo. Our results show that floor plate-derived neuropilin-2 is developmentally regulated, functioning as a molecular sink to sequester semaphorins, preventing premature repulsion of precrossing axons prior to subsequent down-regulation, and allowing for semaphorin-mediated repulsion of post-crossing axons.


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