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Loss of Projections, Functional Compensation, and Residual Deficits in the Mammalian Vestibulospinal System of Hoxb1-Deficient Mice.

Di Bonito M, Boulland JL, Krezel W, Setti E, Studer M, Glover JC - eNeuro (2015)

Bottom Line: Several general motor skills appear unimpaired, but hindlimb vestibulospinal reflexes, which are mediated by the LVST, are greatly reduced.This functional deficit recovers, however, during the second postnatal week, indicating a substantial compensation for the missing LVST.Our results provide a comprehensive account of the developmental role of Hoxb1 in patterning the vestibular system and evidence for a remarkable developmental plasticity in the descending control of reflex limb movements.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institute of Biology Valrose, UMR 7277, University of Nice Sophia Antipolis, 06108 Nice, France; Institute of Biology Valrose, INSERM, U1091, 06108 Nice, France; Institute of Biology Valrose, CNRS, UMR 7277, 06108 Nice, France.

ABSTRACT
The genetic mechanisms underlying the developmental and functional specification of brainstem projection neurons are poorly understood. Here, we use transgenic mouse tools to investigate the role of the gene Hoxb1 in the developmental patterning of vestibular projection neurons, with particular focus on the lateral vestibulospinal tract (LVST). The LVST is the principal pathway that conveys vestibular information to limb-related spinal motor circuits and arose early during vertebrate evolution. We show that the segmental hindbrain expression domain uniquely defined by the rhombomere 4 (r4) Hoxb1 enhancer is the origin of essentially all LVST neurons, but also gives rise to subpopulations of contralateral medial vestibulospinal tract (cMVST) neurons, vestibulo-ocular neurons, and reticulospinal (RS) neurons. In newborn mice homozygous for a Hoxb1- mutation, the r4-derived LVST and cMVST subpopulations fail to form and the r4-derived RS neurons are depleted. Several general motor skills appear unimpaired, but hindlimb vestibulospinal reflexes, which are mediated by the LVST, are greatly reduced. This functional deficit recovers, however, during the second postnatal week, indicating a substantial compensation for the missing LVST. Despite the compensatory plasticity in balance, adult Hoxb1- mice exhibit other behavioral deficits that manifest particularly in proprioception and interlimb coordination during locomotor tasks. Our results provide a comprehensive account of the developmental role of Hoxb1 in patterning the vestibular system and evidence for a remarkable developmental plasticity in the descending control of reflex limb movements. They also suggest an involvement of the lateral vestibulospinal tract in proprioception and in ensuring limb alternation generated by locomotor circuitry.

No MeSH data available.


Related in: MedlinePlus

Behavioral effects of the Hoxb1- mutation in adult mice: righting reflex and open field test. A, Comparison of time required for the righting reflex in wild-type mice (blue) and Hoxb1- (red) mice. B–F, Open field behavior. Naive Hoxb1- mice and their littermate controls were tested during 30 min in the open field, and total distance was scored for three consecutive 10 min time epochs for distance covered (B), total rearing events (C), unsupported rearing (D), leaning (rearing supported against the wall of the arena, E), and time spent in the central zone of the arena (F). Error bars represent SEM. Significant differences with respect to control mice were calculated using the PLSD Fischer test. *p < 0.05 (second and third time bins in D).
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Figure 7: Behavioral effects of the Hoxb1- mutation in adult mice: righting reflex and open field test. A, Comparison of time required for the righting reflex in wild-type mice (blue) and Hoxb1- (red) mice. B–F, Open field behavior. Naive Hoxb1- mice and their littermate controls were tested during 30 min in the open field, and total distance was scored for three consecutive 10 min time epochs for distance covered (B), total rearing events (C), unsupported rearing (D), leaning (rearing supported against the wall of the arena, E), and time spent in the central zone of the arena (F). Error bars represent SEM. Significant differences with respect to control mice were calculated using the PLSD Fischer test. *p < 0.05 (second and third time bins in D).

Mentions: Focusing initially on potential perturbation of the vestibular system, we noted that the righting reflex assessed by the contact righting test, known to be a sensitive measure of equilibrium, was not impaired in Hoxb1- mice (Student’s t test, p > 0.4 for each trial; Fig. 7A). Nor did Hoxb1- mice display head tilting or circling behaviors frequently associated with different types of vestibular dysfunctions (data not shown). Thus, the compensation in the vestibulospinal reflex seen during the second postnatal week evidently translated into a generally normalized capacity for vestibular function in the adult.


Loss of Projections, Functional Compensation, and Residual Deficits in the Mammalian Vestibulospinal System of Hoxb1-Deficient Mice.

Di Bonito M, Boulland JL, Krezel W, Setti E, Studer M, Glover JC - eNeuro (2015)

Behavioral effects of the Hoxb1- mutation in adult mice: righting reflex and open field test. A, Comparison of time required for the righting reflex in wild-type mice (blue) and Hoxb1- (red) mice. B–F, Open field behavior. Naive Hoxb1- mice and their littermate controls were tested during 30 min in the open field, and total distance was scored for three consecutive 10 min time epochs for distance covered (B), total rearing events (C), unsupported rearing (D), leaning (rearing supported against the wall of the arena, E), and time spent in the central zone of the arena (F). Error bars represent SEM. Significant differences with respect to control mice were calculated using the PLSD Fischer test. *p < 0.05 (second and third time bins in D).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4697082&req=5

Figure 7: Behavioral effects of the Hoxb1- mutation in adult mice: righting reflex and open field test. A, Comparison of time required for the righting reflex in wild-type mice (blue) and Hoxb1- (red) mice. B–F, Open field behavior. Naive Hoxb1- mice and their littermate controls were tested during 30 min in the open field, and total distance was scored for three consecutive 10 min time epochs for distance covered (B), total rearing events (C), unsupported rearing (D), leaning (rearing supported against the wall of the arena, E), and time spent in the central zone of the arena (F). Error bars represent SEM. Significant differences with respect to control mice were calculated using the PLSD Fischer test. *p < 0.05 (second and third time bins in D).
Mentions: Focusing initially on potential perturbation of the vestibular system, we noted that the righting reflex assessed by the contact righting test, known to be a sensitive measure of equilibrium, was not impaired in Hoxb1- mice (Student’s t test, p > 0.4 for each trial; Fig. 7A). Nor did Hoxb1- mice display head tilting or circling behaviors frequently associated with different types of vestibular dysfunctions (data not shown). Thus, the compensation in the vestibulospinal reflex seen during the second postnatal week evidently translated into a generally normalized capacity for vestibular function in the adult.

Bottom Line: Several general motor skills appear unimpaired, but hindlimb vestibulospinal reflexes, which are mediated by the LVST, are greatly reduced.This functional deficit recovers, however, during the second postnatal week, indicating a substantial compensation for the missing LVST.Our results provide a comprehensive account of the developmental role of Hoxb1 in patterning the vestibular system and evidence for a remarkable developmental plasticity in the descending control of reflex limb movements.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institute of Biology Valrose, UMR 7277, University of Nice Sophia Antipolis, 06108 Nice, France; Institute of Biology Valrose, INSERM, U1091, 06108 Nice, France; Institute of Biology Valrose, CNRS, UMR 7277, 06108 Nice, France.

ABSTRACT
The genetic mechanisms underlying the developmental and functional specification of brainstem projection neurons are poorly understood. Here, we use transgenic mouse tools to investigate the role of the gene Hoxb1 in the developmental patterning of vestibular projection neurons, with particular focus on the lateral vestibulospinal tract (LVST). The LVST is the principal pathway that conveys vestibular information to limb-related spinal motor circuits and arose early during vertebrate evolution. We show that the segmental hindbrain expression domain uniquely defined by the rhombomere 4 (r4) Hoxb1 enhancer is the origin of essentially all LVST neurons, but also gives rise to subpopulations of contralateral medial vestibulospinal tract (cMVST) neurons, vestibulo-ocular neurons, and reticulospinal (RS) neurons. In newborn mice homozygous for a Hoxb1- mutation, the r4-derived LVST and cMVST subpopulations fail to form and the r4-derived RS neurons are depleted. Several general motor skills appear unimpaired, but hindlimb vestibulospinal reflexes, which are mediated by the LVST, are greatly reduced. This functional deficit recovers, however, during the second postnatal week, indicating a substantial compensation for the missing LVST. Despite the compensatory plasticity in balance, adult Hoxb1- mice exhibit other behavioral deficits that manifest particularly in proprioception and interlimb coordination during locomotor tasks. Our results provide a comprehensive account of the developmental role of Hoxb1 in patterning the vestibular system and evidence for a remarkable developmental plasticity in the descending control of reflex limb movements. They also suggest an involvement of the lateral vestibulospinal tract in proprioception and in ensuring limb alternation generated by locomotor circuitry.

No MeSH data available.


Related in: MedlinePlus