A critical period for the specification of motor pools in the chick lumbosacral spinal cord

Development ◽  
1996 ◽  
Vol 122 (2) ◽  
pp. 659-669 ◽  
Author(s):  
M.P. Matise ◽  
C. Lance-Jones

When 3–4 segments of the chick lumbosacral neural tube are reversed in the anterior-posterior axis at stage 15 (embryonic day 2.5), the spinal cord develops with a reversed organization of motoneurons projecting to individual muscles in the limb (C. Lance-Jones and L. Landmesser (1980) J. Physiol. 302, 581–602). This finding indicated that motoneuron precursors or components of their local environment were specified with respect to target by stage 15. To identify the timing of this event, we have now assessed motoneuron projections after equivalent neural tube reversals at earlier stages of development. Lumbosacral neural tube segments 1–3 (+/− one segment cranial or caudal) were reversed in the anterior-posterior axis at stages 13 and 14 (embryonic day 2). The locations of motoneurons innervating two thigh muscles, the sartorius and femorotibialis, were mapped via retrograde horseradish peroxidase labeling at stages 35–36 (embryonic days 9–10). In a sample of embryos, counts were made of the total number of motoneurons in the lateral motor columns of reversed segments. The majority of motoneurons projecting to the sartorius and femorotibialis were in a normal position within the spinal cord. Segmental differences in motor column size were also similar to normal. These observations indicate that positional cues external to the LS neural tube can affect motoneuron commitment and number at stages 13–14. Since these observations stand in contrast to results following stage 15 reversals, we conclude that regional differences related to motoneuron target identity are normally specified or stabilized within the anterior LS neural tube between stages 14 and 15. To examine the role of the notochord in this process, neural tube reversals were performed at stages 13–14 as described above, except that the underlying notochord was also reversed. Projections to the sartorius and femorotibialis muscles did not differ significantly from those in embryos with neural tube reversals alone, indicating that the notochord is not the source of cues for target identity at stages 13–14.

Development ◽  
2001 ◽  
Vol 128 (12) ◽  
pp. 2255-2268 ◽  
Author(s):  
Cynthia Lance-Jones ◽  
Natalia Omelchenko ◽  
Anya Bailis ◽  
Stephen Lynch ◽  
Kamal Sharma

We have used Hoxd10 expression as a primary marker of the lumbosacral region to examine the early programming of regional characteristics within the posterior spinal cord of the chick embryo. Hoxd10 is uniquely expressed at a high level in the lumbosacral cord, from the earliest stages of motor column formation through stages of motoneuron axon outgrowth. To define the time period when this gene pattern is determined, we assessed Hoxd10 expression after transposition of lumbosacral and thoracic segments at early neural tube stages. We present evidence that there is an early prepattern for Hoxd10 expression in the lumbosacral neural tube; a prepattern that is established at or before stages of neural tube closure. Cells within more posterior lumbosacral segments have a greater ability to develop high level Hoxd10 expression than the most anterior lumbosacral segments or thoracic segments. During subsequent neural tube stages, this prepattern is amplified and stabilized by environmental signals such that all lumbosacral segments acquire the ability to develop high levels of Hoxd10, independent of their axial environment. Results from experiments in which posterior neural segments and/or paraxial mesoderm segments were placed at different axial levels suggest that signals setting Hoxd10 expression form a decreasing posterior-to-anterior gradient. Our experiments do not, however, implicate adjacent paraxial mesoderm as the only source of graded signals. We suggest, instead, that signals from more posterior embryonic regions influence Hoxd10 expression after the early establishment of a regional prepattern. Concurrent analyses of patterns of LIM proteins and motor column organization after experimental surgeries suggest that the programming of these characteristics follows similar rules.


2001 ◽  
Vol 280 (5) ◽  
pp. R1414-R1419 ◽  
Author(s):  
Mitsuharu Yoshiyama ◽  
William C. De Groat

The contribution of different subtypes of α1-adrenoceptors in the lumbosacral spinal cord to the control of the urinary bladder was examined in urethane-anesthetized rats. Bladder pressure was recorded via a transurethral catheter under isovolumetric conditions. Drugs were administered intrathecally at the L6-S1segmental level of spinal cord. RS-100329 (an α1A-antagonist) in doses of 25, 50, and 100 nmol significantly decreased bladder-contraction amplitude by 38%, 52%, and 95%, respectively, whereas (+)-cyclazosin (an α1B-antagonist) significantly decreased bladder-contraction amplitude (48% reduction) only in a 50-nmol but not a 100-nmol dose. Fifty nanomoles of RS-100329 and (+)-cyclazosin increased bladder-contraction frequency by 54% and 44%, respectively. BMY7378 (an α1D-antagonist), in doses of 25, 50, and 100 nmol, did not change bladder activity. These studies suggest that reflex-bladder activity is modulated by two types of spinal α1-adrenergic mechanisms: 1) α1A- or α1B-inhibitory control of the frequency of voiding reflexes presumably mediated by an alteration in the processing of bladder afferent input and 2) α1A-facilitatory modulation of the descending efferent limb of the micturition-reflex pathway. Spinal α1D-adrenoceptors do not appear to have a significant role at either site.


2010 ◽  
Vol 299 (4) ◽  
pp. F785-F791 ◽  
Author(s):  
Masaru Yoshizumi ◽  
Kazumasa Matsumoto-Miyai ◽  
Akihiko Yonezawa ◽  
Masahito Kawatani

α1-Adrenergic receptor subtypes are widely distributed in the central nervous system and are involved in autonomic functions such as micturition. We investigated the presence and the role of supraspinal and/or spinal α1-adrenergic receptors in modulating the micturition reflex in conscious female Wistar rats. The expression of α1-adrenergic receptor subtypes in rat brain and lumbosacral spinal cord was studied using RT-PCR. Continuous-infusion cystometrograms were obtained in conscious rats, and α1-adrenergic receptor antagonists were administered via intracerebroventricular or intrathecal routes. The mRNA expression of α1A-, α1B-, and α1D-adrenergic receptors was detected in rat brain (midbrain and pons) and lumbosacral spinal cord (dorsal and ventral parts of spinal cord). In addition, intracerebroventricular injection of the α1-adrenergic receptor antagonist tamsulosin (1–10 μg), the selective α1A-adrenergic receptor antagonist silodosin (1–10 μg), and the selective α1D-adrenergic receptor antagonist BMY 7378 (1–10 μg) significantly prolonged the intercontraction interval (ICI) but did not alter maximum voiding pressure (MVP). Although intrathecal injection of BMY 7378 (0.0001–10 μg) did not affect ICI, tamsulosin and silodosin prolonged ICI in a dose-dependent manner. MVP was significantly reduced by intrathecal injection of tamsulosin (10 μg) but not by silodosin or BMY 7378 (0.0001–10 μg). Supraspinal α1A- and α1D-adrenergic receptors are apparently important for the regulation of reflex-bladder activity in conscious rats. Noradrenergic projection from the brain stem to the lumbosacral spinal cord may promote the afferent limb rather than the efferent limb of the micturition reflex pathway via α1A-adrenergic receptors.


2018 ◽  
Vol 6 (3) ◽  
pp. 22 ◽  
Author(s):  
Diana Juriloff ◽  
Muriel Harris

The human neural tube defects (NTD), anencephaly, spina bifida and craniorachischisis, originate from a failure of the embryonic neural tube to close. Human NTD are relatively common and both complex and heterogeneous in genetic origin, but the genetic variants and developmental mechanisms are largely unknown. Here we review the numerous studies, mainly in mice, of normal neural tube closure, the mechanisms of failure caused by specific gene mutations, and the evolution of the vertebrate cranial neural tube and its genetic processes, seeking insights into the etiology of human NTD. We find evidence of many regions along the anterior–posterior axis each differing in some aspect of neural tube closure—morphology, cell behavior, specific genes required—and conclude that the etiology of NTD is likely to be partly specific to the anterior–posterior location of the defect and also genetically heterogeneous. We revisit the hypotheses explaining the excess of females among cranial NTD cases in mice and humans and new developments in understanding the role of the folate pathway in NTD. Finally, we demonstrate that evidence from mouse mutants strongly supports the search for digenic or oligogenic etiology in human NTD of all types.


Development ◽  
1996 ◽  
Vol 122 (3) ◽  
pp. 905-914 ◽  
Author(s):  
M. Fukushima ◽  
M. Nakamura ◽  
K. Ohta ◽  
R. Okamura ◽  
A. Negi

Cek8 and low affinity NGF receptor (LNGFR) are expressed at high levels on the chick spinal motoneurons of the brachial and lumbar segments from embryonic day (E) 5 to E7, but weakly on the motoneurons of the non-limb-innervating segments. We determined by means of heterotopic neural tube transplantation, that the expression of these molecules was already intrinsically determined at E2. We used these spatiotemporal specific molecules as markers of motoneuron subpopulations. To analyze how motoneurons acquire regional specification along the anterior-posterior (A-P) axis and in the transverse plane, we observed the expression of these molecules on ectopic motoneurons induced by implanting a supernumerary notochord or floor plate at E2. The ectopic motoneurons induced by the graft obtained from either the thoracic or lumbar segments had the same expression profile as the normal motoneurons at each A-P level. These findings suggest that regional specification of motoneurons, at least of Cek8 and LNGFR expression, is independent of the notochord and the floor plate and that the whole neural tube appears to be committed to differentiate into the motoneuron subtypes along the A-P axis at the operative stages.


Development ◽  
1997 ◽  
Vol 124 (19) ◽  
pp. 3805-3814 ◽  
Author(s):  
M. Epstein ◽  
G. Pillemer ◽  
R. Yelin ◽  
J.K. Yisraeli ◽  
A. Fainsod

Patterning along the anterior-posterior axis takes place during gastrulation and early neurulation. Homeobox genes like Otx-2 and members of the Hox family have been implicated in this process. The caudal genes in Drosophila and C. elegans have been shown to determine posterior fates. In vertebrates, the caudal genes begin their expression during gastrulation and they take up a posterior position. By injecting sense and antisense RNA of the Xenopus caudal gene Xcad-2, we have studied a number of regulatory interactions among homeobox genes along the anterior-posterior axis. Initially, the Xcad-2 and Otx-2 genes are mutually repressed and, by late gastrulation, they mark the posterior- or anterior-most domains of the embryo, respectively. During late gastrulation and neurulation, Xcad-2 plays an additional regulatory function in relation to the Hox genes. Hox genes normally expressed anteriorly are repressed by Xcad-2 overexpression while those normally expressed posteriorly exhibit more anterior expression. The results show that the caudal genes are part of a posterior determining network which during early gastrulation functions in the subdivision of the embryo into anterior head and trunk domains. Later in gastrulation and neurulation these genes play a role in the patterning of the trunk region.


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