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Cell Migration and Layer/Nuclear Formation

開催日 2014/9/11
時間 16:00 - 17:00
会場 Poster / Exhibition(Event Hall B)

Sharp turn of tangentially-migrating hindbrain neurons controlled by modulating responsiveness to attractive midline via chemokine signalling and cAMP

  • P1-088
  • Zhu Yan / Yan Zhu:1 村上 富士夫 / Fujio Murakami:1 
  • 1:大阪大学大学院 生命機能研究科 / Graduate School of Frontier Biosciences, Osaka University, Japan 

Tangential migration is employed to construct the complex mammalian brain by
transporting neurons over long distances to destinations far from their birth places, thus enabling neuronal types from distant origins to interact and connect efficiently. The precision of long distance tangential migration is clearly important for the subsequent circuit formation. How neurons that are migrating in complex tissue environment integrate and/or prioritize multiple environment signals and make precise directional decisions is still far from complete understanding.

To address this issue, we have studied the long distance migration of pontine neurons (PN) in mouse hindbrain. These neurons born from the lower rhombic lip migrate anteriorly within the hindbrain alar plate, and just before reaching the root of trigeminal ganglion they make a sharp turn towards the ventral midline. The midline-directed migration was shown before to be attracted by Netrin in and around the floor plate (Yee et al, 1999, Neuron, 24, p607). Our previous observation that PN prematurely turn to ventral midline in CXCL12/CXCR4 mutants (Zhu et al, 2009, Developoment, 136, p1919) prompted us to hypothesize that the position and timing of the sharp ventral turning is controlled by switching Netrin responsiveness from a suppressed state during anterior migration to an activated state at the turning point. Here, we present evidence that stimulating CXCL12/CXCR4 signalling in PN dampens the attractive response of PN towards the floor plate. This dampening effect is mimicked by lowering the cAMP level pharmacologically, but is alleviated by increasing the cAMP level. Together these results suggest that attractive response of PN to midline is supressed by CXCL12/CXCR4 signalling possibly via regulating the cAMP level. We then established a culture method where whole hindbrains were cultured in rotating bottles. We show that this method could successfully recapitulate the sophisticated PN migration in their natural three dimensional tissue environment. Using this culture paradigm in combination with in utero electroporation, we are exploring further mechanisms at tissue and molecular levels that underlie the cellular decisions at a migratory turning point.

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