Regional variations in the extent and timing of motoneuron cell death in the lumbosacral spinal cord of the chick embryo

doi:10.1016/0165-3806(87)90210-0

Developmental Brain Research

Volume 34, Issue 2, August 1987, Pages 215-221

https://doi.org/10.1016/0165-3806(87)90210-0 Get rights and content

Abstract

We have examined the distribution of motoneurons in different segments of the chick lumbosacral spinal cord before and after the period of motoneuron cell death. The extent of cell death was found to be greatest at the boundaries of the lumbosacral cord where over 60% of the motoneurons died and least in the central region where only 30% died. After cell death at stage 40 the number of motoneurons in each segment was linearly correlated with segment length, suggesting that growth of the segment and motoneuron numbers may be regulated by a common factor. The time of completion of motoneuron cell death exhibited a rostrocaudal gradient along the lumbar cord. Cell death was complete in the anterior segments by stage 35 but not until stage 38 in the caudal 4 segments. The regional variations in the extent and timing of motoneuron cell death suggest that the relative importance of the factors mediating cell death vary in different regions of the lumbar cord.

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There are more references available in the full text version of this article.

Cited by (19)

Neuromuscular synapses mediate motor axon branching and motoneuron survival during the embryonic period of programmed cell death
2003, Developmental Biology
The embryonic period of motoneuron programmed cell death (PCD) is marked by transient motor axon branching, but the role of neuromuscular synapses in regulating motoneuron number and axonal branching is not known. Here, we test whether neuromuscular synapses are required for the quantitative association between reduced skeletal muscle contraction, increased motor neurite branching, and increased motoneuron survival. We achieved this by comparing agrin and rapsyn mutant mice that lack acetylcholine receptor (AChR) clusters. There were significant reductions in nerve-evoked skeletal muscle contraction, increases in intramuscular axonal branching, and increases in spinal motoneuron survival in agrin and rapsyn mutant mice compared with their wild-type littermates at embryonic day 18.5 (E18.5). The maximum nerve-evoked skeletal muscle contraction was reduced a further 17% in agrin mutants than in rapsyn mutants. This correlated to an increase in motor axon branch extension and number that was 38% more in agrin mutants than in rapsyn mutants. This suggests that specializations of the neuromuscular synapse that ensure efficient synaptic transmission and muscle contraction are also vital mediators of motor axon branching. However, these increases in motor axon branching did not correlate with increases in motoneuron survival when comparing agrin and rapsyn mutants. Thus, agrin-induced synaptic specializations are required for skeletal muscle to effectively control motoneuron numbers during embryonic development.
The spatial-temporal gradient of naturally occurring motoneuron death reflects the time of prior exit from the cell cycle and position within the lateral motor column
1999, Developmental Biology
Embryonic lumbar spinal motoneurons (MNs) are characterized by a period of programmed cell death (PCD) that spans several days and occurs in a rostrocaudal gradient. The generation of these MNs also takes place in a temporal–spatial gradient, such that MNs within rostral lumbar segments exit the cell cycle earlier and MNs within progressively caudal regions are born later. In vitro studies have shown that the latest born spinal MNs, presumably through the possession of endogenous “survival properties,” are also the last to acquire their trophic dependence. If the birth date and therefore spinal cord location of lumbar spinal MNs influence the spatial–temporal pattern of PCD, then earlier born MNs should die sooner and be located more rostrally than those generated later. Alternatively, if the time at which MNs die during development is unrelated to their prior exit from the cell cycle, those born at various phases should die throughout the period of PCD. We report here that lumbar MNs generated during the earliest part (embryonic day 2–3) of the proliferative period in the developing chick spinal cord tend to die during the earliest stages of the PCD period and that MNs born in successive 12-h intervals die at correspondingly later periods during PCD. Furthermore, the spatial progression of PCD of these subpopulations of MNs occurs in a rostrocaudal gradient. Finally, while MNs do appear to die in a mediolateral gradient during the period of MN PCD, this pattern is only partly accounted for by MNs born in consecutive intervals. These data support the notion that the timing and rostrocaudal location of MNs undergoing PCD reflect their time of exit from the cell cycle.
Patterns of programmed cell death in populations of developing spinal motoneurons in chicken, mouse, and rat
1999, Developmental Biology
During embryonic development, approximately one-half of the spinal motoneurons initially generated are lost during a wave of programmed cell death (PCD). Classical studies in this system laid the basis of much work on the role and control of neuronal cell death during development. However, we have little information concerning the timing of cell death in motoneuron pools at different rostrocaudal levels, especially in rodents. We developed a novel protocol for whole-mount TUNEL labeling that allows apoptotic nuclei to be visualized in whole-mount preparations of embryonic spinal cord; double labeling with antibodies to Islet 1/2 showed that nearly all TUNEL-positive cells were motoneurons. In chicken and mouse embryos, the density of TUNEL-positive nuclei was specifically increased following target ablation. The pattern of naturally occurring motoneuron PCD was studied in spinal cords from different species and ages: chick (E4.5–E9.0), mouse (E11.5–E15.5), and rat (E13.5–E16.5). In all species, motoneuron PCD is first apparent at cervical levels and last at sacral levels. However, motoneuron PCD does not follow a strict rostrocaudal sequence. Following cervical motoneuron PCD, TUNEL profiles are first observed at lumbar levels in chick but at thoracic levels in rat. At a given rostrocaudal level, medial motoneurons tend to die before lateral populations, but here too there are exceptions. Motoneuron cell death is thus regulated in a highly stereotyped manner during development of vertebrate spinal cord. Our technique will provide a basis for the monitoring even localized changes in this pattern.
Functionally related motor neuron pool and muscle sensory afferent subtypes defined by coordinate ETS gene expression
1998, Cell
Motor function depends on the formation of selective connections between sensory and motor neurons and their muscle targets. The molecular basis of the specificity inherent in this sensory-motor circuit remains unclear. We show that motor neuron pools and subsets of muscle sensory afferents can be defined by the expression of ETS genes, notably PEA3 and ER81. There is a matching in PEA3 and ER81 expression by functionally interconnected sensory and motor neurons. ETS gene expression by motor and sensory neurons fails to occur after limb ablation, suggesting that their expression is coordinated by signals from the periphery. ETS genes may therefore participate in the development of selective sensory-motor circuits in the spinal cord.
Development of muscle afferents in the spinal cord of the tammar wallaby
1998, Developmental Brain Research
The development of muscle afferents in the tammar wallaby was examined to address whether proprioceptive input contributes to the marked asymmetry of the fore and hindlimb movement. Anatomical tracing with biocytin showed that the muscle afferents had reached the brachial motor horn by postnatal day (P1), but were less advanced in the lumbar region. Labelled cells lying outside the motor horn, presumably filled via gap junctions, were evident in the neonatal lumbar cord. By the 4th postnatal week, the afferent innervation of both brachial and lumbar cords became similar. Afferent discharges from stretching the biceps muscle could be recorded at birth, but not until P4 from the hindlimb gastrocnemius muscle. The discharges were predominantly phasic until P35 when tonic activity could also be recorded. Short latency spinal reflex responses superimposed upon a longer lasting potential were present in the brachial cord at birth, appearing in the lumbar cord at P4. By the 3rd postnatal week, spinal reflex became comparable in both segmental levels. The time course of muscle afferent development was compared to the progression of natural cell death in the lumbar cord. Sensorimotor connections were established towards the end of the rapid phase cell death as observed in other vertebrates.
Transient expression of somatostatin messenger RNA and peptide in the hypoglossal nucleus of the neonatal rat
1991, Developmental Brain Research
The postnatal developmental expression of somatostatin mRNA and peptide in the rat hypoglossal nucleus was analyzed using immunocytochemical and in situ hybridization techniques. Both the neuropeptide and its cognate mRNA were found to be transiently present within a subpopulation of hypoglossal motoneurons during the neonatal period. At the day of birth, a large population of perikarya situated in caudal, ventral regions of the hypoglossal nucleus expressed somatostatin. By postnatal day 7, the number of hypoglossal somata which expressed somatostatin had diminished considerably, and by 2 weeks postnatal, only few such cell bodies were found. By 3–4 weeks postnatal, somatostatin peptide- and mRNA-containing hypoglossal motoneurons were rarely observed, and in the adult, they were never detected, despite the use of colchicine. A double-labeling co-localization technique was used to demonstrate that somatostatin, when present perinatally, always coexisted with calcitonin gene-related peptide in hypoglossal motoneurons. The latter peptide, in contrast to somatostatin, was expressed in large numbers of somata throughout the entire hypoglossal nucleus and persisted within the motoneurons throughout development into adulthood. These results demonstrate that somatostatin is transiently expressed in motoneurons of the caudal, ventral tier of the hypoglossal nucleus in the neonatal rat. The developmental disappearance of somatostatin is most likely not due to cell death; hypoglossal somata continue to express calcitonin gene-related peptide, with which somatostatin coexisted perinatally, at high levels throughout development. Thus, it appears that the regulation of somatostatin in expression in hypoglossal neurons occurs at the level of gene transcription or mRNA stability/degradation. The restricted temporal and spatial distribution suggests that somatostatin may have a role in some developmental aspect of a population of hypoglossal motoneurons which function to protrude the tongue.

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Developmental Brain Research

Abstract

References (20)

Ontogeny of leg motor output in the chick embryo: a neural analysis

Brain Res.

Dorsal root ganglion removal in Rana pipiens produces fewer motoneurons

Brain Res.

An autoradiographic study of the formation of the lateral motor column in the chick embryo

Brain Res.

The retrograde transport of horseradish peroxidase from the developing limb of the chick embryo

Brain Res.

Regression versus peripheral control of differentiation in motor hypoplasia

Am. J. Anat.

Cell death in the development of the lateral motor column of the chick embryo

J. Comp. Neurol.

The developmental history of the motoneuron

Neurosci. Res. Bull.

A series of normal stages in the development of the chick embryo

J. Morphol.

Organization of motor pools in the chick lumbar lateral motor column

J. Comp. Neurol.

Reduction of the naturally occurring motor neuron loss by enlargement of the periphery

J. Comp. Neurol.

Cited by (19)

Neuromuscular synapses mediate motor axon branching and motoneuron survival during the embryonic period of programmed cell death

The spatial-temporal gradient of naturally occurring motoneuron death reflects the time of prior exit from the cell cycle and position within the lateral motor column

Patterns of programmed cell death in populations of developing spinal motoneurons in chicken, mouse, and rat

Functionally related motor neuron pool and muscle sensory afferent subtypes defined by coordinate ETS gene expression

Development of muscle afferents in the spinal cord of the tammar wallaby

Transient expression of somatostatin messenger RNA and peptide in the hypoglossal nucleus of the neonatal rat

Research reportRegional variations in the extent and timing of motoneuron cell death in the lumbosacral spinal cord of the chick embryo

Abstract

Brain Res.

Brain Res.

Brain Res.

Brain Res.

Regression versus peripheral control of differentiation in motor hypoplasia

Am. J. Anat.

Cell death in the development of the lateral motor column of the chick embryo

J. Comp. Neurol.

The developmental history of the motoneuron

Neurosci. Res. Bull.

A series of normal stages in the development of the chick embryo

J. Morphol.

Organization of motor pools in the chick lumbar lateral motor column

J. Comp. Neurol.

Reduction of the naturally occurring motor neuron loss by enlargement of the periphery

J. Comp. Neurol.

Research report
Regional variations in the extent and timing of motoneuron cell death in the lumbosacral spinal cord of the chick embryo