Netrin-1 Confines Rhombic Lip-Derived Neurons to the CNS

Publication date: 13 February 2018
Source:Cell Reports, Volume 22, Issue 7
Author(s): Andrea R. Yung, Noah R. Druckenbrod, Jean-François Cloutier, Zhuhao Wu, Marc Tessier-Lavigne, Lisa V. Goodrich
During brainstem development, newborn neurons originating from the rhombic lip embark on exceptionally long migrations to generate nuclei important for audition, movement, and respiration. Along the way, this highly motile population passes several cranial nerves yet remains confined to the CNS. We found that Ntn1 accumulates beneath the pial surface separating the CNS from the PNS, with gaps at nerve entry sites. In mice null for Ntn1 or its receptor DCC, hindbrain neurons enter cranial nerves and migrate into the periphery. CNS neurons also escape when Ntn1 is selectively lost from the sub-pial region (SPR), and conversely, expression of Ntn1 throughout the mutant hindbrain can prevent their departure. These findings identify a permissive role for Ntn1 in maintaining the CNS-PNS boundary. We propose that Ntn1 confines rhombic lip-derived neurons by providing a preferred substrate for tangentially migrating neurons in the SPR, preventing their entry into nerve roots.

Graphical abstract

Teaser

Yung et al. show that Ntn1 prevents pontine neurons from migrating into the periphery along cranial nerves by providing a preferred substrate in the sub-pial region. These findings introduce a local, permissive role for Ntn1 in the maintenance of the CNS-PNS boundary in the developing mouse hindbrain.


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