Motoneuron cell death in the developing lumbar spinal cord of the mouse

Lance‐Jones, Cynthia

doi:10.1016/0165-3806(82)90192-4

Cited by 224 publications

(74 citation statements)

References 33 publications

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“…Mouse spinal cord has six lumbar segments, with hindlimb muscles being innervated by LMC motoneurons in segments L1-L5 (Lance-Jones, 1982;Lin and Carpenter, 2003;Tarchini et al, 2005). All three Hox10 transcripts were first detected in lumbar spinal cord at E10.5, and the rostrocaudal expression domain of each did not change in any of the ages examined (data not shown).…”

Section: Hoxc10mentioning

confidence: 90%

Hoxc10 and Hoxd10 regulate mouse columnar, divisional and motor pool identity of lumbar motoneurons

Wang

Scott

et al. 2008

Development

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A central question in neural development is how the broad diversity of neurons is generated in the vertebrate CNS. We have investigated the function of Hoxc10 and Hoxd10 in mouse lumbar motoneuron development. We show that Hoxc10 and Hoxd10 are initially expressed in most newly generated lumbar motoneurons, but subsequently become restricted to the lateral division of the lateral motor column (lLMC). Disruption of Hoxc10 and Hoxd10 caused severe hindlimb locomotor defects. Motoneurons in rostral lumbar segments were found to adopt the phenotype of thoracic motoneurons. More caudally the lLMC and dorsalprojecting axons were missing, yet most hindlimb muscles were innervated. The loss of the lLMC was not due to decreased production of motoneuron precursors or increased apoptosis. Instead, presumptive lLMC neurons failed to migrate to their normal position, and did not differentiate into other motoneurons or interneurons. Together, these results show that Hoxc10 and Hoxd10 play key roles in establishing lumbar motoneuron columnar, divisional and motor pool identity.

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Section: Hoxc10mentioning

confidence: 90%

Hoxc10 and Hoxd10 regulate mouse columnar, divisional and motor pool identity of lumbar motoneurons

Wang

Scott

et al. 2008

Development

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“…This was the earliest time that motoneurons in the mouse spinal cord could be retrogradely labeled by the injection of HRP into the limbs. Second, counts of motoneuronal cell bodies throughout embryogenesis indicate that the period of cell death in the motoneuronal pool begins at about day 14 in the mouse, with a precipitous drop in the number of cells occurring between 14 and 15 d in term (Flanagan, 1969;Lance-Jones, 1982). Therefore, injections just prior to this time would be expected to label the maximum number of motoneurons.…”

Section: Discussionmentioning

confidence: 99%

Fluorescence-activated cell sorting of embryonic mouse and rat motoneurons and their long-term survival in vitro

1987

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Motoneurons from embryonic mice and rats were labeled with retrogradely transported succinyl wheat germ agglutinin (WGA)-fluorescein isothiocyanate (FITC). After dissociation of the spinal cord, fluorescent motoneurons were isolated by flow cytometry. Sorted motoneurons were maintained for as long as 6 weeks in vitro on monolayers of astrocytes in muscle-conditioned medium. Immunocytochemical staining of the cultures for various neuronal antigens suggested that sorted motoneurons are receptive to GABAergic and glycinergic, as well as cholinergic, innervation. Many of the sorted cells were also labeled intracellularly with antibodies to choline acetyltransferase (ChAT) and GABA.

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“…This period includes the time of neurogenesis for almost all neurons and glial cells in the spinal cord (Altman and Bayer, 1984;Nornes and Carry, 1978;Sims and Vaughn, 1979), as well as the early stages of process outgrowth and synaptogenesis by the neurons (Flanagan, 1969; Holley et , 1982a-c;Lance-Jones, 1982;Wentworth, 1984a, b). Thus, most or all cell types in the spinal cord should be tractable to analysis or isolation by cell sorting from the earliest developmental stages.…”

Section: Discussionmentioning

confidence: 99%

“…Although axons and dendrites have already begun to develop in vivo at E12.5 (Flanagan, 1969;Holley et al, 1982a-c;Lance-Jones, 1982;Wentworth, 1984a, b), most were sheared off during dissociation, leaving only cell bodies and subcellular fragments.…”

Section: Spinal Cordmentioning

confidence: 99%

Analysis and isolation of embryonic mammalian neurons by fluorescence- activated cell sorting

et al. 1986

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Cells were dissociated from the CNS of the embryonic mouse and rat to produce cell suspensions suitable for analysis and separation on a fluorescence-activated cell sorter (FACS). Cells from the spinal cord of the embryonic mouse were analyzed in the most detail. Cell suspensions generated three major peaks in histograms of forward-angle light scatter. Examination of material isolated from each peak and labeling of cell suspensions with the nonvital and supravital fluorescent dyes propidiurn iodide, ethidium bromide, and acridine orange demonstrated that the three peaks represented live cells, dead cells, and subcellular fragments. Passage through the cell sorter did not detectably damage live cells, as shown by light microscopy, FACS analysis, and in vitro culture of sorted cells. Neurons and glial cells collected by sorting survived at least 4 weeks in culture.Cell suspensions dissociated from the dorsal root ganglia, hippocampus, hypothalamus, cerebellum, and cerebral cortex of the embryonic mouse and from the spinal cord of the embryonic rat produced similar results. Analysis of samples prepared at different developmental stages showed that viable cells could be recovered from each of these regions throughout the important stages of neurogenesis and early cellular differentiation, but that few viable cells could be recovered from animals beyond late embryonic or early postnatal ages.Quantitative FACS analysis of monoclonal antibody A2B5, tetanus toxin and cholera toxin, and lectins binding to live dissociated cells from the embryonic spinal cord demonstrated that these cells had already developed binding sites for these cellsurface ligands by embryonic day 13.These results demonstrate that a fluorescence-activated cell sorter can be used for quantitative analysis of specific cellular properties, that FACS analysis and sorting can be used to identify and isolate live cells from many regions of the embryonic mammalian CNS during important developmental periods, and that sorted neurons and glial cells can be maintained for weeks in culture.Understanding of cellular development and intercellular interactions in the developing nervous system is a fundamental goal in neurobiology. However, the vast numbers of cell types and the complexity of their interactions can make in vivo studies of cellular mechanisms difficult, if not impossible. The use of tissue culture allows studies at a level of detail usually not possible in vivo. However, most primary cultures contain a mixture of cell types, which usually cannot be distinguished on the basis of morphology, thus making it difficult or impossible to identify

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Motoneuron cell death in the developing lumbar spinal cord of the mouse

Cited by 224 publications

References 33 publications

Hoxc10 and Hoxd10 regulate mouse columnar, divisional and motor pool identity of lumbar motoneurons

Hoxc10 and Hoxd10 regulate mouse columnar, divisional and motor pool identity of lumbar motoneurons

Fluorescence-activated cell sorting of embryonic mouse and rat motoneurons and their long-term survival in vitro

Analysis and isolation of embryonic mammalian neurons by fluorescence- activated cell sorting

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