TY - JOUR
T1 - Subdomain-mediated axon-axon signaling and chemoattraction cooperate to regulate afferent innervation of the lateral habenula
AU - Schmidt, Ewoud Roberto Eduard
AU - Brignani, Sara
AU - Adolfs, Youri
AU - Lemstra, Suzanne
AU - Demmers, Jeroen
AU - Vidaki, Marina
AU - Donahoo, Amber Lee Skye
AU - Lilleväli, Kersti
AU - Vasar, Eero
AU - Richards, Linda Jane
AU - Karagogeos, Domna
AU - Kolk, Sharon Margriet
AU - Pasterkamp, Ronald Jeroen
N1 - Funding Information:
We thank members of the R.J.P. laboratory for assistance and discussions and Alex Kolodkin and Guillermina Lopez-Bendito for reading the manuscript. We thank Marc Tessier-Lavigne, Anton Berns, Cecilia Flores, Wolfgang Wurst, Alain Chedotal, Meng Li, Seji Miyata, and Helen Cooper for sharing reagents and mice. We thank Nicoletta Kessaris and Jerre van Veluw for advice and technical assistance. Anti-Tag1 and anti-LAMP antibodies were obtained from the Developmental Studies Hybridoma Bank. This study is supported by grants from the Netherlands Organization for Scientific Research (TopTalent; to E.R.E.S.), Stichting Parkinson Fonds, the Netherlands Organization for Health Research and Development (VIDI, ZonMW-TOP), the European Union (mdDANeurodev, FP7/2007-2011, Grant 222999), and the People Programme (Marie Curie Actions) of the European Union’s Seventh Framework Programme FP7/2007-2013/under REA grant agreement number [289581] (NPlast) (to R.J.P.). This study was partly performed within the framework of Dutch Top Institute Pharma Project T5-207 (to R.J.P.). This work was partly supported by project grants (631466 and 1043045) from the National Health and Medical Research Council, Australia (NHMRC). L.J.R. was supported by an NHMRC Principal Research fellowship, A.-L.S.D was supported by an Australian Post-graduate Award scholarship and a top-up scholarship from the QBI, and E.V. was supported by an Institutional investigation grant (IUT20-41) from the Estonian Research Council.
PY - 2014/7/16
Y1 - 2014/7/16
N2 - A dominant feature of neural circuitry is the organization of neuronal projections and synapses into specific brain nuclei or laminae. Lamina-specific connectivity is controlled by the selective expression of extracellular guidance and adhesion molecules in the target field. However, how (sub)nucleus-specific connections are established and whether axon-derived cues contribute to subdomain targeting are largely unknown. Here, we demonstrate that the lateral subnucleus of the habenula (lHb) determines its own afferent innervation by sending out efferent projections that express the cell adhesion molecule LAMP to reciprocally collect and guide dopaminergic afferents to the lHb-a phenomenon we term subdomain-mediated axon-axon signaling. This process of reciprocal axon-axon interactions cooperates with lHb-specific chemoattraction mediated by Netrin-1, which controls axon target entry, to ensure specific innervation of the lHb. We propose that cooperation between pretarget reciprocal axon-axon signaling and subdomain-restricted instructive cues provides a highly precise and general mechanism to establish subdomain-specific neural circuitry.
AB - A dominant feature of neural circuitry is the organization of neuronal projections and synapses into specific brain nuclei or laminae. Lamina-specific connectivity is controlled by the selective expression of extracellular guidance and adhesion molecules in the target field. However, how (sub)nucleus-specific connections are established and whether axon-derived cues contribute to subdomain targeting are largely unknown. Here, we demonstrate that the lateral subnucleus of the habenula (lHb) determines its own afferent innervation by sending out efferent projections that express the cell adhesion molecule LAMP to reciprocally collect and guide dopaminergic afferents to the lHb-a phenomenon we term subdomain-mediated axon-axon signaling. This process of reciprocal axon-axon interactions cooperates with lHb-specific chemoattraction mediated by Netrin-1, which controls axon target entry, to ensure specific innervation of the lHb. We propose that cooperation between pretarget reciprocal axon-axon signaling and subdomain-restricted instructive cues provides a highly precise and general mechanism to establish subdomain-specific neural circuitry.
UR - http://www.scopus.com/inward/record.url?scp=84904344844&partnerID=8YFLogxK
U2 - 10.1016/j.neuron.2014.05.036
DO - 10.1016/j.neuron.2014.05.036
M3 - Article
C2 - 25033181
AN - SCOPUS:84904344844
SN - 0896-6273
VL - 83
SP - 372
EP - 387
JO - Neuron
JF - Neuron
IS - 2
ER -