Protease nexin I (PNI) is a member of the family of serine protease inhibitors (serpins) that have been shown to promote neurite outgrowth in vitro from different neuronal cell types. These include neuroblastoma cells, hippocampal neurons, and sympathetic neurons. Free PNI protein is markedly decreased in various anatomical brain regions, including hippocampus, of patients with Alzheimer diseas...

Accurate pathfinding is a crucial step in formation of a functional nervous system. Individually identified zebrafish primary motoneurons undergo a stereotyped temporal sequence of axonal outgrowth and pathway selection during which their growth cones follow a common pathway to a "choice point" and then select divergent cell-specific pathways that lead to separate muscle territories. The charac...

The importance of neural activity and motoneuronal cell death in the formation of specific synaptic connections between muscle afferents and motoneurons was studied in chick embryos. Patterned neural activity was blocked by applying d-tubocurarine (dtc) chronically to embryos during the period when sensory-motor connections are formed [stages (St) 28-42]. Dtc blocks neurogenic muscle contractio...

The quantitative matching hypothesis of neuronal cell death was tested for the chick hindlimb by determining the relationship between myotube number at the onset of motoneuron cell death and the number of motoneurons that survive in chicks, quail, and chick-quail chimeras. Hindlimb buds, which differ in size between the 2 species, were exchanged at stages 16 1/2-19, myosin ATPase-stained myotub...

Several protocols direct human embryonic stem cells (hESCs) toward differentiation into functional motoneurons, but the efficiency of motoneuron generation varies based on the human ESC line used. We aimed to develop a novel protocol to increase the formation of motoneurons from human ESCs. In this study, we tested a nuclear histone deacetylase protein, Sirt1, to promote neural precursor cell (...

Previous reports from this laboratory have shown that the chronic treatment of chick embryos with neuromuscular blocking agents (e.g., curare, alpha-bungarotoxin), during the period of naturally occurring cell death of spinal motoneurons (days 5 to 10), greatly reduces the amount of cell death in this system. The surviving motoneurons continue differentiation and innervate the peripheral muscul...

Mitra P, Brownstone RM. An in vitro spinal cord slice preparation for recording from lumbar motoneurons of the adult mouse. J Neurophysiol 107: 728–741, 2012. First published October 26, 2011; doi:10.1152/jn.00558.2011.—The development of central nervous system slice preparations for electrophysiological studies has led to an explosion of knowledge of neuronal properties in health and disease. ...

Dye-, tracer- and electrotonic coupling were studied independently in genioglossal (GG) motoneurons using intracellular recordings in in vitro brainstem slices from rats postnatal ages 1-30 days. The subpopulation of GG motoneurons were retrogradely labeled after an injection of dextran-rhodamine into the posterior tongue. Dye-coupling was studied with Lucifer yellow injected into 55 motoneuron...

Motoneurons are an essential component of all metazoan nervous systems, but it is unknown whether there is an evolutionarily conserved mechanism for generating motoneurons during neurogenesis. In the vertebrate CNS, HB9/MNR2 transcription factors are specifically expressed in all somatic motoneurons and are necessary to distinguish motoneurons from interneurons, in part by repressing interneuro...

Ciliary neutrophic factor (CNTF) can enhance motoneuron survival during naturally occurring cell death in the chick (Oppenheim et al, 1991). Because receptors for CNTF are expressed in both motoneurons and their target muscles (Davis et al., 1991; lp et al., 1993), both tissues are potential sites of CNTF action in development. We examined the ability of CNTF to prevent the degeneration of a ne...