Journal
MOLECULAR AND CELLULAR NEUROSCIENCE
Volume 39, Issue 4, Pages 529-538Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.mcn.2008.07.023
Keywords
DCC; Netrin; Locus coeruleus; Tangential migration; Alar plate; Rhombomere 1; Development
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Funding
- National Natural Science Foundation of China [30525014, 30628016, 30570637]
- Ministry of Science and Technology of China [2006CB806601, 2006CB500808, 2007CB512303]
- Chinese Academy of Sciences [KSCX2-YW-R-35, KSCX2-YW-R-100]
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The tangential migration from the dorsal rhombomere (r) 1 to the dorsolateral pontine tegmentum is a crucial event in the development of locus coeruleus (LC), but the molecular mechanisms underlying the migration are not well Understood. We show that the Netrin receptor DCC is expressed in LC neurons and is required for their tangential migration. In DCC-/- embryos, fate determination of LC neurons appeared normal but tangential migration failed to initiate properly. Although many LC neurons eventually reached the a Substantial number of LC dorsolateral pontine tegmentum in DCC-/- embryos at late embryonic stages, neurons were abnormally distributed in the rostral pons and cerebellum. In DCCkanga mice that lack the intracellular P3 domain of DCC, these defects were not observed. In addition, although Unc5h3, another Netrin receptor, was expressed in the dorsal r1, Unc5h3(-/-) mice exhibited the normal LC morphology and gene expression profiles in the LC compared with wild-type mice. Thus, our findings demonstrate that DCC is a key regulator of tangential migration of LC neurons during the embryonic development. (C) 2008 Published by Elsevier Inc.
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