Gli2 is required for induction of floor plate and adjacent cells, but not most ventral neurons in the mouse central nervous system

Development ◽  
1998 ◽  
Vol 125 (15) ◽  
pp. 2759-2770 ◽  
Author(s):  
M.P. Matise ◽  
D.J. Epstein ◽  
H.L. Park ◽  
K.A. Platt ◽  
A.L. Joyner

Induction of the floor plate at the ventral midline of the neural tube is one of the earliest events in the establishment of dorsoventral (d/v) polarity in the vertebrate central nervous system (CNS). The secreted molecule, Sonic hedgehog, has been shown to be both necessary and sufficient for this induction. In vertebrates, several downstream components of this signalling pathway have been identified, including members of the Gli transcription factor family. In this study, we have examined d/v patterning of the CNS in Gli2 mouse mutants. We have found that the floor plate throughout the midbrain, hindbrain and spinal cord does not form in Gli2 homozygotes. Despite this, motoneurons and ventral interneurons form in their normal d/v positions at 9.5 to 12.5 days postcoitum (dpc). However, cells that are generated in the region flanking the floor plate, including dopaminergic and serotonergic neurons, were greatly reduced in number or absent in Gli2 homozygous embryos. These results suggest that early signals derived from the notochord can be sufficient for establishing the basic d/v domains of cell differentiation in the ventral spinal cord and hindbrain. Interestingly, the notochord in Gli2 mutants does not regress ventrally after 10.5 dpc, as in normal embryos. Finally, the spinal cord of Gli1/Gli2 zinc-finger-deletion double homozygous mutants appeared similar to Gli2 homozygotes, indicating that neither gene is required downstream of Shh for the early development of ventral cell fates outside the ventral midline.

2017 ◽  
Vol 61 (3-4-5) ◽  
pp. 257-265 ◽  
Author(s):  
Sophie Khazanov ◽  
Yael Paz ◽  
Amit Hefetz ◽  
Ben J. Gonzales ◽  
Yaara Netser ◽  
...  

Development ◽  
1991 ◽  
Vol 113 (2) ◽  
pp. 625-639 ◽  
Author(s):  
P. Bovolenta ◽  
J. Dodd

The floor plate of the vertebrate nervous system has been implicated in the guidance of commissural axons at the ventral midline. Experiments in chick have also suggested that at earlier stages of development the floor plate induces the differentiation of motor neurons and other neurons of the ventral spinal cord. Here we have examined the development of the spinal cord in a mouse mutant, Danforth's short-tail, in which the floor plate is absent from caudal regions of the neuraxis. In affected regions of the spinal cord, commissural axons exhibited aberrant projection patterns as they reached and crossed the ventral midline. In addition, motor neurons were absent or markedly reduced in number in regions of the spinal cord lacking a floor plate. Our results suggest that the floor plate is indeed an intermediate target in the projection of commissural axons and support the idea that several different mechanisms operate in concert in the guidance of axons to their cellular targets in the developing nervous system. In addition, these experiments suggest that the mechanisms that govern the differentiation of the floor plate and other ventral cell types in the neural tube are common to mammals and lower vertebrates.


2020 ◽  
Author(s):  
Kalaimakan Hervé Arulkandarajah ◽  
Guillaume Osterstock ◽  
Agathe Lafont ◽  
Hervé Le Corronc ◽  
Nathalie Escalas ◽  
...  

SUMMARYIn the developing central nervous system, electrical signaling is thought to rely exclusively on differentiating neurons as they acquire the ability to generate action potentials. Accordingly, the neuroepithelial progenitors (NEPs) giving rise to all neurons and glial cells during development have been reported to remain electrically passive. Here, we investigated the physiological properties of NEPs in the mouse spinal cord at the onset of spontaneous neural activity (SNA) initiating motor behavior in embryos. Using patch-clamp recordings, we discovered that spinal NEPs exhibit spontaneous membrane depolarizations during episodes of SNA. These recurrent depolarizations exhibited a ventral-to-dorsal gradient with the highest amplitude located in the floor-plate – the ventral-most part of the neuroepithelium. Paired-recordings revealed that NEPs are extensively coupled via gap-junctions and form a single electrical syncytium. Although other NEPs were electrically passive, we discovered that floor-plate NEPs have the unique ability to generate large Na+/Ca++ action potentials. Unlike neurons, floor-plate action potentials relied primarily on the activation of voltage-gated T-type calcium channels (TTCCs). In situ hybridization showed that all 3 known subtypes of TTCCs are highly and predominantly expressed in the floor-plate. During SNA, we found that acetylcholine released by motoneurons recurrently trigger floor-plate action potentials by acting through nicotinic acetylcholine receptors. Finally, by expressing the genetically encoded calcium indicator GCaMP6f in the floor plate, we demonstrated that neuroepithelial action potentials are associated with calcium waves and propagate along the entire length of the spinal cord. By unraveling a novel physiological mechanism generating electrical signals which can propagate independently from neurons across a neural structure, our work significantly changes our understanding of the development, origin and extent of electrical signaling in the central nervous system.HIGHLIGHTSSpinal neuroepithelial progenitors (NEP) are depolarized during spontaneous neural activityNEPs form a single electrical syncytium connected by gap junctionsFloor-plate NEPs generate large Na+/Ca++ action potentials in response to acetylcholineNeuroepithelial action potentials propagate across the entire spinal cord


2018 ◽  
Vol 23 (1) ◽  
pp. 10-13
Author(s):  
James B. Talmage ◽  
Jay Blaisdell

Abstract Injuries that affect the central nervous system (CNS) can be catastrophic because they involve the brain or spinal cord, and determining the underlying clinical cause of impairment is essential in using the AMA Guides to the Evaluation of Permanent Impairment (AMA Guides), in part because the AMA Guides addresses neurological impairment in several chapters. Unlike the musculoskeletal chapters, Chapter 13, The Central and Peripheral Nervous System, does not use grades, grade modifiers, and a net adjustment formula; rather the chapter uses an approach that is similar to that in prior editions of the AMA Guides. The following steps can be used to perform a CNS rating: 1) evaluate all four major categories of cerebral impairment, and choose the one that is most severe; 2) rate the single most severe cerebral impairment of the four major categories; 3) rate all other impairments that are due to neurogenic problems; and 4) combine the rating of the single most severe category of cerebral impairment with the ratings of all other impairments. Because some neurological dysfunctions are rated elsewhere in the AMA Guides, Sixth Edition, the evaluator may consult Table 13-1 to verify the appropriate chapter to use.


1963 ◽  
Vol 44 (3) ◽  
pp. 475-480 ◽  
Author(s):  
R. Grinberg

ABSTRACT Radiologically thyroidectomized female Swiss mice were injected intraperitoneally with 131I-labeled thyroxine (T4*), and were studied at time intervals of 30 minutes and 4, 28, 48 and 72 hours after injection, 10 mice for each time interval. The organs of the central nervous system and the pituitary glands were chromatographed, and likewise serum from the same animal. The chromatographic studies revealed a compound with the same mobility as 131I-labeled triiodothyronine in the organs of the CNS and in the pituitary gland, but this compound was not present in the serum. In most of the chromatographic studies, the peaks for I, T4 and T3 coincided with those for the standards. In several instances, however, such an exact coincidence was lacking. A tentative explanation for the presence of T3* in the pituitary gland following the injection of T4* is a deiodinating system in the pituitary gland or else the capacity of the pituitary gland to concentrate T3* formed in other organs. The presence of T3* is apparently a characteristic of most of the CNS (brain, midbrain, medulla and spinal cord); but in the case of the optic nerve, the compound is not present under the conditions of this study.


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