Analysis of expression pattern and genetic deletion of Netrin5 in the developing mouse

Andrew M. Garrett, Thomas J. Jucius, Liam P.R. Sigaud, Fu Lei Tang, Wen Cheng Xiong, Susan L. Ackerman, Robert W. Burgess

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

Boundary cap cells (BCC) are a transient, neural-crest-derived population found at the motor exit point (MEP) and dorsal root entry zone (DREZ) of the embryonic spinal cord. These cells contribute to the central/peripheral nervous system (CNS/PNS) boundary, and in their absence neurons and glia from the CNS migrate into the PNS. We found Netrin5 (Ntn5), a previously unstudied member of the netrin gene family, to be robustly expressed in BCC. We generated Ntn5 knockout mice and examined neurodevelopmental and BCC-related phenotypes. No abnormalities in cranial nerve guidance, dorsal root organization, or sensory projections were found. However, Ntn5 mutant embryos did have ectopic motor neurons (MNs) that migrated out of the ventral horn and into the motor roots. Previous studies have implicated semaphorin6A (Sema6A) in BCC signaling to plexinA2 (PlxnA2)/neuropilin2 (Nrp2) in MNs in restricting MN cell bodies to the ventral horn, particularly in the caudal spinal cord. In Ntn5 mutants, ectopic MNs are likely to be a different population, as more ectopias were found rostrally. Furthermore, ectopic MNs in Ntn5 mutants were not immunoreactive for NRP2. The netrin receptor deleted in colorectal cancer (DCC) is a potential receptor for NTN5 in MNs, as similar ectopic neurons were found in Dcc mutant mice, but not in mice deficient for other netrin receptors. Thus, Ntn5 is a novel netrin family member that is expressed in BCC, functioning to prevent MN migration out of the CNS.

Original languageEnglish (US)
Article number3
JournalFrontiers in Molecular Neuroscience
Volume9
Issue numberJAN
DOIs
StatePublished - Jan 26 2016

Keywords

  • Axon guidance
  • Chemorepulsion
  • Dorsal root entry zone
  • Motor exit point

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience

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    Garrett, A. M., Jucius, T. J., Sigaud, L. P. R., Tang, F. L., Xiong, W. C., Ackerman, S. L., & Burgess, R. W. (2016). Analysis of expression pattern and genetic deletion of Netrin5 in the developing mouse. Frontiers in Molecular Neuroscience, 9(JAN), [3]. https://doi.org/10.3389/fnmol.2016.00003