Netrin-1 is crucial for the establishment of the dorsal column-medial lemniscal system.
The dorsal column-medial lemniscal system is a significant sensory pathway that mediates touch and limb position sense. In this system, axons from the second-order neurons in the dorsal column nuclei form the internal arcuate fibers, cross the ventral midline (floor plate) within the medulla oblongata, and then project to the thalamus as the medial lemniscus. Here we demonstrate that Netrin-1, which is secreted from the floor plate in the medulla oblongata, is indispensable to the formation of the dorsal column-medial lemniscal system. Axons from the dorsal column nuclei cross the midline at around embryonic day 11 in mice. Concurrently, Netrin-1 mRNA and its receptor DCC (deleted in colorectal cancer) were expressed in the floor plate and commissural axons there, respectively. In our explant culture experiments, the floor plates of the embryonic 11-day-old mutant Netrin-1 homozygous mice did not attract axons from the dorsal column nuclei of ICR mice, while those from the wild type littermates did. Moreover, we observed that although the dorsal column nuclei developed in situ in mutant mice, their axons were not attracted toward the floor plate: they did not cross midline and remained ipsilaterally, without forming the internal arcuate fibers, in embryonic 17-day-old mutant Netrin-1 homozygous mice.
Kubota
Chikara
C
Division of Cell Biology and Neuroscience, Department of Morphological and Physiological Sciences, Faculty of Medical Sciences, University of Fukui, 23 Shimoaizuki, Matsuoka, Fukui 910-1193, Japan.
Nagano
Takashi
T
Baba
Hisatoshi
H
Sato
Makoto
M
D000344:Afferent Pathways / Q000196:embryology* / Q000378:metabolism*; D000818:Animals; D001369:Axons / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000096:biosynthesis; D002478:Cells, Cultured; D000075389:DCC Receptor; D005456:Fluorescent Dyes; D006720:Homozygote; D008297:Male; D008526:Medulla Oblongata / Q000196:embryology* / Q000378:metabolism*; D008636:Mesencephalon / Q000196:embryology / Q000378:metabolism*; D051379:Mice; D008813:Mice, Inbred ICR; D008817:Mice, Mutant Strains; D009414:Nerve Growth Factors / Q000235:genetics / Q000502:physiology*; D000075388:Netrin-1; D016501:Neurites / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011956:Receptors, Cell Surface; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis
D015815:Cell Adhesion Molecules; D000075389:DCC Receptor; C501910:Dcc protein, mouse; D005456:Fluorescent Dyes; D009414:Nerve Growth Factors; C000617353:Ntn1 protein, mouse; C000617354:Ntn1 protein, rat; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D025521:Tumor Suppressor Proteins; D000075388:Netrin-1