Non cell-autonomous role of DCC in the guidance of the corticospinal tract at the midline.
DCC, a NETRIN-1 receptor, is considered as a cell-autonomous regulator for midline guidance of many commissural populations in the central nervous system. The corticospinal tract (CST), the principal motor pathway for voluntary movements, crosses the anatomic midline at the pyramidal decussation. CST fails to cross the midline in Kanga mice expressing a truncated DCC protein. Humans with heterozygous DCC mutations have congenital mirror movements (CMM). As CMM has been associated, in some cases, with malformations of the pyramidal decussation, DCC might also be involved in this process in human. Here, we investigated the role of DCC in CST midline crossing both in human and mice. First, we demonstrate by multimodal approaches, that patients with CMM due to DCC mutations have an increased proportion of ipsilateral CST projections. Second, we show that in contrast to Kanga mice, the anatomy of the CST is not altered in mice with a deletion of DCC in the CST. Altogether, these results indicate that DCC controls CST midline crossing in both humans and mice, and that this process is non cell-autonomous in mice. Our data unravel a new level of complexity in the role of DCC in CST guidance at the midline.
Sorbonne Universités, UPMC Univ Paris 06, INSERM U 1127, CNRS UMR 7225, Institut du Cerveau et de la Moelle épinière, F-75013, Paris, France.|Sorbonne Universités, UPMC Univ Paris 06, INSERM, CNRS, Institut de Biologie Paris Seine, Neuroscience Paris Seine, F-75005, Paris, France.
Quentin
Q
Welniarz
Sorbonne Universités, UPMC Univ Paris 06, INSERM, CNRS, Institut de Biologie Paris Seine, Neuroscience Paris Seine, F-75005, Paris, France.
Marie-Pierre
MP
Morel
Sorbonne Universités, UPMC Univ Paris 06, INSERM U 1127, CNRS UMR 7225, Institut du Cerveau et de la Moelle épinière, F-75013, Paris, France.|Sorbonne Universités, UPMC Univ Paris 06, INSERM, CNRS, Institut de Biologie Paris Seine, Neuroscience Paris Seine, F-75005, Paris, France.
Oriane
O
Pourchet
Sorbonne Universités, UPMC Univ Paris 06, INSERM U 1127, CNRS UMR 7225, Institut du Cerveau et de la Moelle épinière, F-75013, Paris, France.
Cécile
C
Gallea
Sorbonne Universités, UPMC Univ Paris 06, INSERM U 1127, CNRS UMR 7225, Institut du Cerveau et de la Moelle épinière, F-75013, Paris, France.
Jean-Charles
JC
Lamy
Unità Operativa di Neurologia-Firenze, Azienda USL Toscana Centro, Ospedale San Giovanni di Dio, 50143, Firenze, Italy.
Massimo
M
Cincotta
Sorbonne Universités, UPMC Univ Paris 06, INSERM, CNRS, Institut de Biologie Paris Seine, Adaptation Biologique et vieillissement, F-75005, Paris, France.
Mohamed
M
Doulazmi
Sorbonne Universités, UPMC Univ Paris 06, INSERM, CNRS, Institut de la Vision, F-75012, Paris, France.
Morgane
M
Belle
Sorbonne Universités, UPMC Univ Paris 06, INSERM U 1127, CNRS UMR 7225, Institut du Cerveau et de la Moelle épinière, F-75013, Paris, France.|Département de Neurologie, AP-HP, Hôpital Pitié Salpêtrière, Paris, France.
Aurélie
A
Méneret
Sorbonne Universités, UPMC Univ Paris 06, INSERM U 1127, CNRS UMR 7225, Institut du Cerveau et de la Moelle épinière, F-75013, Paris, France.
Oriane
O
Trouillard
Sorbonne Universités, UPMC Univ Paris 06, INSERM U 1127, CNRS UMR 7225, Institut du Cerveau et de la Moelle épinière, F-75013, Paris, France.
Marta
M
Ruiz
Centre d'Investigation Clinique 14-22, INSERM/AP-HP, Paris, France.
Vanessa
V
Brochard
Sorbonne Universités, UPMC Univ Paris 06, INSERM U 1127, CNRS UMR 7225, Institut du Cerveau et de la Moelle épinière, F-75013, Paris, France.
Sabine
S
Meunier
Sorbonne Universités, UPMC Univ Paris 06, INSERM, CNRS, Institut de Biologie Paris Seine, Neuroscience Paris Seine, F-75005, Paris, France.
Alain
A
Trembleau
Sorbonne Universités, UPMC Univ Paris 06, INSERM U 1127, CNRS UMR 7225, Institut du Cerveau et de la Moelle épinière, F-75013, Paris, France.|Département de Neurologie, AP-HP, Hôpital Pitié Salpêtrière, Paris, France.
Marie
M
Vidailhet
Sorbonne Universités, UPMC Univ Paris 06, INSERM, CNRS, Institut de la Vision, F-75012, Paris, France.
Alain
0000-0001-7577-3794
A
Chédotal
Sorbonne Universités, UPMC Univ Paris 06, INSERM, CNRS, Institut de Biologie Paris Seine, Neuroscience Paris Seine, F-75005, Paris, France.
Isabelle
I
Dusart
Sorbonne Universités, UPMC Univ Paris 06, INSERM U 1127, CNRS UMR 7225, Institut du Cerveau et de la Moelle épinière, F-75013, Paris, France. emmanuel.flamand-roze@psl.aphp.fr.|Département de Neurologie, AP-HP, Hôpital Pitié Salpêtrière, Paris, France. emmanuel.flamand-roze@psl.aphp.fr.
Emmanuel
E
Roze
D000328:Adult; D000368:Aged; D000818:Animals; D000071437:Axon Guidance; D001369:Axons / Q000378:metabolism; D003337:Corpus Callosum / Q000378:metabolism; D000075389:DCC Receptor / Q000235:genetics / Q000502:physiology*; D019054:Evoked Potentials, Motor; D005260:Female; D006225:Hand / Q000294:innervation / Q000503:physiopathology; D006801:Humans; D008297:Male; D008822:Mice, Transgenic; D008875:Middle Aged; D009044:Motor Cortex / Q000503:physiopathology; D009068:Movement; D019579:Neocortex / Q000378:metabolism; D011712:Pyramidal Tracts / Q000473:pathology* / Q000503:physiopathology*; D050781:Transcranial Magnetic Stimulation
D000075389:DCC Receptor; C501909:DCC protein, human; C501910:Dcc protein, mouse