Suchergebnisse

The interpeduncular nucleus (IPN) is a hindbrain structure formed by three main subdivisions, the prodromal (Pro) domain located at the isthmus (Ist), and the rostral and caudal interpeduncular domains (IPR, IPC) within rhombomere 1 (r1). Various cell populations can be detected in the IPN through the expression of the Nkx6.1, Otp, Otx2, Pax7, and/or Irx2 transcription factors. These cell populations follow independent dorsoventral tangential and radial migratory routes targeting the ventral paramedian region of Ist and r1. Here we set out to examine the influence of the Netrin-1/DCC pathway on these migrations, since it is known to regulate other processes of neuronal migration in the brain. To this end, we analyzed IPN development in late gestational wild-type and DCC–/– mice, using mainly in situ hybridization (ISH) to identify the cells expressing each of the aforementioned genes. We found that the migration of Nkx6.1+ and Irx2+ cells into the Pro domain was strongly disrupted by the loss of DCC, as occurred with the migration of Pax7+, Irx2+, and Otp+ cells that would normally form the IPR. In addition, there was mild impairment of the migration of the Pax7+ and Otx2+ cells that form the IPC. These results demonstrate that the Netrin-1/DCC signaling pathway is involved in the migration of most of the IPN populations, mainly affecting those of the Pro and IPR domains of this nucleus. There are psychiatric disorders that involve the medial habenula (mHb)-IPN system, so that this experimental model could provide a basis to study their neurodevelopmental etiology. ; This work was funded by the Seneca Foundation to LP (Autonomous Community of Murcia, Excellency Research contract, reference: 19904/GERM/15; 5672 Fundación Séneca; project name: Genoarchitectonic Brain Development and Applications to Neurodegenerative Diseases and Cancer) and by the Knowledge Generation Program of the Spanish Government to GL-B (PGC2018-096631-B-I00). IG-G was recipient of a predoctoral fellowship of the FPU program from the University of Murcia. ; Peer reviewed

PMID:17392456 ; The function of the nervous system depends on the precision of axon wiring during development. Previous studies have demonstrated that Slits, a family of secreted chemorepellent proteins, are crucial for the proper development of several major forebrain tracts. Mice deficient in Slit2 or, even more so, in both Slit1 and Slit2 have defects in multiple axonal pathways, including corticofugal, thalamocortical, and callosal connections. In the spinal cord, members of the Robo family of proteins help mediate the function of Slits, but the relative contribution of these receptors to the guidance of forebrain projections remains to be determined. In the present study, we addressed the function of Robo1 and Robo2 in the guidance of forebrain projections by analyzing Robo1-, Robo2-, and Robo1;Robo2-deficient mice. Mice deficient in Robo2 and, more dramatically, in both Robo1 and Robo2, display prominent axon guidance errors in the development of corticofugal, thalamocortical, and corticocortical callosal connections. Our results demonstrate that Robo1 and Robo2 mostly cooperate to mediate the function of Slit proteins in guiding the major forebrain projections. ; This work was supported by grants from Spanish Government (BFU2005-04773/BMC) and the European Young Investigator (EURYI) program (O.M.) and from Association pour la Recherche sur le Cancer (A.C.). ; Peer reviewed

15 pages, 9 figures.-- Supporting information (Suppl. figs S1-S3) available at: http://biology.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pbio.1000098#toclink6 ; The establishment of connectivity between specific thalamic nuclei and cortical areas involves a dynamic interplay between the guidance of thalamocortical axons and the elaboration of cortical areas in response to appropriate innervation. We show here that Sema6A mutants provide a unique model to test current ideas on the interactions between subcortical and cortical guidance mechanisms and cortical regionalization. In these mutants, axons from the dorsal lateral geniculate nucleus (dLGN) are misrouted in the ventral telencephalon. This leads to invasion of presumptive visual cortex by somatosensory thalamic axons at embryonic stages. Remarkably, the misrouted dLGN axons are able to find their way to the visual cortex via alternate routes at postnatal stages and reestablish a normal pattern of thalamocortical connectivity. These findings emphasize the importance and specificity of cortical cues in establishing thalamocortical connectivity and the spectacular capacity of the early postnatal cortex for remapping initial sensory representations. ; This work was supported by grants from Science Foundation Ireland (01/F1/B006) to KJM, Spanish Ministry of Science and Innovation (grants BFU2006–00408 and CONSOLIDER-INGENIO 2010 CSD2007–00023) to GLB, and a Medical Research Council (MRC) Career Establishment Award (G0300200) and Project Grant (G0700377) to ZM. AC is supported by the Fondation pour la Recherche Medicale (programme équipe FRM). GL has been supported by a Government of Ireland Scholarship, awarded by the Irish Research Council of Science, Engineering and Technology. AR was supported by a Health Research Board Postdoctoral Fellowship. ; Peer reviewed