Genetic dissection of axonal hindbrain commissures
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1
inserm UMRS968, equipe 1, Institut de la Vision, France
In all bilateria, a variety of axon tracts cross the midline of the central nervous system, forming well-defined commissures. In mammals, the function of commissures is well established in the forebrain and visual system, but much less understood at other axial levels. We used the emerging knowledge of axon guidance mechanisms to dissect the function of several commissures in the hindbrain. It has been shown that the receptor Robo3 acts as a master regulator of midline crossing in growing axons in mice and humans. Moreover, patients suffering from Horizontal Gaze Palsy with Progressive Scoliosis disease (HGPPS) bear homozygous Robo3 mutations, and have uncrossed dorsal median lemniscus and pyramidal tracts. We show that site-specific deletions of the Robo3 receptor using the Cre-lox system result in the absence of select commissures in the sensory, motor or sensorimotor systems and lead to specific functional deficits. Krox20::cre; Robo3lox/lox mice are lacking commissures in the 3rd and 5th rhombomeres. Although the abducens (VIth oculomotor nerve) is still projecting to the lateral rectus muscle, DiI tracing reveals the absence of internuclear crossed projection from the abducens to the oculomotor (IIIrd) nucleus. These mice exhibit defects in horizontal (but not vertical) eye movements. They also have uncrossed projection from the the aVCN (anterior Ventral Cochlear Nucleus) to the MNTB (Median Nucleus of the Trapezoid Body) associated with abnormal Acoustic BrainStem Response diagrams. Ptf1a::cre; Robo3lox/lox mice are strongly ataxic and have mostly uncrossed axonal projections from the Inferior Olive. Some Cre; Robo3 lines represent good models for HGPPS and other human syndromes. Thus, the Robo3 conditional allele is a powerful genetic tool to probe the precise functions of individual commissures and to identify the cellular substrate of related human dysfunction.
Conference:
3rd Mediterranean Conference of Neuroscience , Alexandria, Egypt, 13 Dec - 16 Dec, 2009.
Presentation Type:
Poster Presentation
Topic:
CNS Diseases
Citation:
Renier
N,
Schonewille
M,
Giraudet
F,
Avan
P,
Zeeuw
CD and
Chedotal
A
(2009). Genetic dissection of axonal hindbrain commissures.
Front. Neurosci.
Conference Abstract:
3rd Mediterranean Conference of Neuroscience .
doi: 10.3389/conf.neuro.01.2009.16.155
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Received:
25 Nov 2009;
Published Online:
25 Nov 2009.
*
Correspondence:
Nicolas Renier, inserm UMRS968, equipe 1, Institut de la Vision, Paris, France, nicolas.renier@inserm.fr