Cerebral Cortex Advance Access originally published online on April 8, 2009
Cerebral Cortex 2009 19(Supplement 1):i11-i21; doi:10.1093/cercor/bhp027
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This article appears in the following Cerebral Cortex issue: Cortical Development: Neural Stem Cells to Neural Circuits Chania, Greece, May 22-25, 2008 [View the issue table of contents]
Neuropilin 1-Sema Signaling Regulates Crossing of Cingulate Pioneering Axons during Development of the Corpus Callosum
1 Queensland Brain Institute, 2 The School of Biomedical Sciences, The University of Queensland, Brisbane, Queensland 4072, Australia, 3 Deptartment of Anatomy and Neurobiology and the Program in Neuroscience, University of Maryland, Baltimore, School of Medicine, Baltimore, MD 21201, USA, 4 Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, 37077 Göttingen, Germany, 5 Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA
Address correspondence to email: richards{at}uq.edu.au.
Pioneer axons from the cingulate cortex initiate corpus callosum (CC) development, yet nothing is known about the molecules that regulate their guidance. We demonstrate that neuropilin 1 (Npn1) plays an integral role in the development of the CC. Npn1 is localized to axons of cingulate neurons as they cross the midline, and multiple class 3 semaphorins (Semas) are expressed around the developing CC, implicating these guidance molecules in the regulation of Npn1-expressing axons emanating from the cingulate cortex. Furthermore, axons from the cingulate cortex display guidance errors in Npn1Sema- mice, a knockin mouse line in which Npn1 is unable to bind Semas. Analysis of mice deficient in the transcription factor Emx2 demonstrated that the cingulate cortex of these mice was significantly reduced in comparison to wild-type controls at E17 and that the CC was absent in rostral sections. Expression of Npn1 was absent in rostral sections of Emx2 mutants, suggesting that Npn1-expressing cingulate pioneers are required for CC formation. These data highlight a central role for Npn1 in the development of projections from the cingulate cortex and further illustrate the importance of these pioneer axons in the formation of the CC.
Key Words: axon guidance • cingulate cortex • Emx2 • neuropilin 1 • Sema
Michael Piper and Céline Plachez contributed equally to this work.