FGF8 induces formation of an ectopic isthmic organizer and isthmocerebellar development via a repressive effect on Otx2 expression

Development ◽  
1999 ◽  
Vol 126 (6) ◽  
pp. 1189-1200 ◽  
Author(s):  
S. Martinez ◽  
P.H. Crossley ◽  
I. Cobos ◽  
J.L. Rubenstein ◽  
G.R. Martin

Beads containing recombinant FGF8 (FGF8-beads) were implanted in the prospective caudal diencephalon or midbrain of chick embryos at stages 9–12. This induced the neuroepithelium rostral and caudal to the FGF8-bead to form two ectopic, mirror-image midbrains. Furthermore, cells in direct contact with the bead formed an outgrowth that protruded laterally from the neural tube. Tissue within such lateral outgrowths developed proximally into isthmic nuclei and distally into a cerebellum-like structure. These morphogenetic effects were apparently due to FGF8-mediated changes in gene expression in the vicinity of the bead, including a repressive effect on Otx2 and an inductive effect on En1, Fgf8 and Wnt1 expression. The ectopic Fgf8 and Wnt1 expression domains formed nearly complete concentric rings around the FGF8-bead, with the Wnt1 ring outermost. These observations suggest that FGF8 induces the formation of a ring-like ectopic signaling center (organizer) in the lateral wall of the brain, similar to the one that normally encircles the neural tube at the isthmic constriction, which is located at the boundary between the prospective midbrain and hindbrain. This ectopic isthmic organizer apparently sends long-range patterning signals both rostrally and caudally, resulting in the development of the two ectopic midbrains. Interestingly, our data suggest that these inductive signals spread readily in a caudal direction, but are inhibited from spreading rostrally across diencephalic neuromere boundaries. These results provide insights into the mechanism by which FGF8 induces an ectopic organizer and suggest that a negative feedback loop between Fgf8 and Otx2 plays a key role in patterning the midbrain and anterior hindbrain.

Development ◽  
2000 ◽  
Vol 127 (9) ◽  
pp. 1857-1867 ◽  
Author(s):  
K.A. Adams ◽  
J.M. Maida ◽  
J.A. Golden ◽  
R.D. Riddle

Cells in the caudal mesencephalon and rostral metencephalon become organized by signals emanating from the isthmus organizer (IsO). The IsO is associated with the isthmus, a morphological constriction of the neural tube which eventually defines the mesencephalic/ metencephalic boundary (MMB). Here we report that the transcription factor Lmx1b is expressed and functions in a distinct region of the IsO. Lmx1b expression is maintained by the glycoprotein Fgf8, a signal capable of mediating IsO signaling. Lmx1b, in turn, maintains the expression of the secreted factor Wnt1. Our conclusions are substantiated by the following: (i) Lmx1b mRNA becomes localized to the isthmus immediately after Fgf8 initiation, (ii) Wnt1 expression is localized to the Lmx1b expression domain, but with slightly later kinetics, (iii) Fgf8-soaked beads generate similar domains of expression for Lmx1b and Wnt1 and (iv) retroviral-mediated expression of Lmx1b (Lmx1b/RCAS) maintains Wnt1 expression in the mesencephalon. Ectopic Lmx1b is insufficient to alter the expression of a number of other genes expressed at the IsO, suggesting that it does not generate a new signaling center. Instead, if we allow Lmx1b/RCAS-infected brains to develop longer, we detect changes in mesencephalic morphology. Since both ectopic and endogenous Lmx1b expression occurs in regions of the isthmus undergoing morphological changes, it could normally play a role in this process. Furthermore, a similar phenotype is not observed in Wnt1/RCAS-infected brains, demonstrating that ectopic Wnt1 is insufficient to mediate the effect of ectopic Lmx1b in our assay. Since Wnt1 function has been linked to the proper segregation of mesencephalic and metencephalic cells, we suggest that Lmx1b and Wnt1 normally function in concert to affect IsO morphogenesis.


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.


2021 ◽  
Vol 11 (8) ◽  
pp. 3397
Author(s):  
Gustavo Assunção ◽  
Nuno Gonçalves ◽  
Paulo Menezes

Human beings have developed fantastic abilities to integrate information from various sensory sources exploring their inherent complementarity. Perceptual capabilities are therefore heightened, enabling, for instance, the well-known "cocktail party" and McGurk effects, i.e., speech disambiguation from a panoply of sound signals. This fusion ability is also key in refining the perception of sound source location, as in distinguishing whose voice is being heard in a group conversation. Furthermore, neuroscience has successfully identified the superior colliculus region in the brain as the one responsible for this modality fusion, with a handful of biological models having been proposed to approach its underlying neurophysiological process. Deriving inspiration from one of these models, this paper presents a methodology for effectively fusing correlated auditory and visual information for active speaker detection. Such an ability can have a wide range of applications, from teleconferencing systems to social robotics. The detection approach initially routes auditory and visual information through two specialized neural network structures. The resulting embeddings are fused via a novel layer based on the superior colliculus, whose topological structure emulates spatial neuron cross-mapping of unimodal perceptual fields. The validation process employed two publicly available datasets, with achieved results confirming and greatly surpassing initial expectations.


2016 ◽  
Vol 74 (8) ◽  
pp. 632-637 ◽  
Author(s):  
Vernon Furtado da Silva ◽  
Mauricio Rocha Calomeni ◽  
Rodolfo Alkmim Moreira Nunes ◽  
Carlos Elias Pimentel ◽  
Gabriela Paes Martins ◽  
...  

ABSTRACT This study focused upon the functional capacity of mirror neurons in autistic children. 30 individuals, 10 carriers of the autistic syndrome (GCA), 10 with intellectual impairments (GDI), and 10 non-autistics (GCN) had registered eletroencephalogram from the brain area theoretically related to mirror neurons. Data collection procedure occurred prior to brain stimulation and after the stimulation session. During the second session, participants had to alternately process figures evoking neutral, happy, and/or sorrowful feelings. Results proved that, for all groups, the stimulation process in fact produced additional activation in the neural area under study. The level of activation was related to the format of emotional stimuli and the likelihood of boosting such stimuli. Since the increase of activation occurred in a model similar to the one observed for the control group, we may suggest that the difficulty people with autism have at expressing emotions is not due to nonexistence of mirror neurons.


2014 ◽  
Vol 43 (2) ◽  
pp. 218-223 ◽  
Author(s):  
Diego Blanco ◽  
José M. Vázquez ◽  
Miguel A. Rivero ◽  
Juan A. Corbera ◽  
Alberto Arencibia

2017 ◽  
Vol 19 (3) ◽  
pp. 349-377
Author(s):  
Leonardo Niro Nascimento

This article first aims to demonstrate the different ways the work of the English neurologist John Hughlings Jackson influenced Freud. It argues that these can be summarized in six points. It is further argued that the framework proposed by Jackson continued to be pursued by twentieth-century neuroscientists such as Papez, MacLean and Panksepp in terms of tripartite hierarchical evolutionary models. Finally, the account presented here aims to shed light on the analogies encountered by psychodynamically oriented neuroscientists, between contemporary accounts of the anatomy and physiology of the nervous system on the one hand, and Freudian models of the mind on the other. These parallels, I will suggest, are not coincidental. They have a historical underpinning, as both accounts most likely originate from a common source: John Hughlings Jackson's tripartite evolutionary hierarchical view of the brain.


2018 ◽  
Vol 43 (1) ◽  
pp. 180-189 ◽  
Author(s):  
Kanako Saito ◽  
Ryotaro Kawasoe ◽  
Hiroshi Sasaki ◽  
Ayano Kawaguchi ◽  
Takaki Miyata

Abstract Spatiotemporally ordered production of cells is essential for brain development. Normally, most undifferentiated neural progenitor cells (NPCs) face the apical (ventricular) surface of embryonic brain walls. Pathological detachment of NPCs from the apical surface and their invasion of outer neuronal territories, i.e., formation of NPC heterotopias, can disrupt the overall structure of the brain. Although NPC heterotopias have previously been observed in a variety of experimental contexts, the underlying mechanisms remain largely unknown. Yes-associated protein 1 (Yap1) and the TEA domain (Tead) proteins, which act downstream of Hippo signaling, enhance the stem-like characteristics of NPCs. Elevated expression of Yap1 or Tead in the neural tube (future spinal cord) induces massive NPC heterotopias, but Yap/Tead-induced expansion of NPCs in the developing brain has not been previously reported to produce NPC heterotopias. To determine whether NPC heterotopias occur in a regionally characteristic manner, we introduced the Yap1-S112A or Tead-VP16 into NPCs of the telencephalon and diencephalon, two neighboring but distinct forebrain regions, of embryonic day 10 mice by in utero electroporation, and compared NPC heterotopia formation. Although NPCs in both regions exhibited enhanced stem-like behaviors, heterotopias were larger and more frequent in the diencephalon than in the telencephalon. This result, the first example of Yap/Tead-induced NPC heterotopia in the forebrain, reveals that Yap/Tead-induced NPC heterotopia is not specific to the neural tube, and also suggests that this phenomenon depends on regional factors such as the three-dimensional geometry and assembly of these cells.


Author(s):  
Tim Palmer

It is proposed that both human creativity and human consciousness are (unintended) consequences of the human brain’s extraordinary energy efficiency. The topics of creativity and consciousness are treated separately, though have a common sub-structure. It is argued that creativity arises from a synergy between two cognitive modes of the human brain (which broadly coincide with Kahneman’s Systems 1 and 2). In the first, available energy is spread across a relatively large network of neurons. As such, the amount of energy per active neuron is so small that the operation of such neurons is susceptible to thermal (ultimately quantum decoherent) noise. In the second, available energy is focussed on a small enough subset of neurons to guarantee a deterministic operation. An illustration of how this synergy can lead to creativity with implications for computing in silicon are discussed. Starting with a discussion of the concept of free will, the notion of consciousness is defined in terms of an awareness of what are perceived to be nearby counterfactual worlds in state space. It is argued that such awareness arises from an interplay between our memories on the one hand, and quantum physical mechanisms (where, unlike in classical physics, nearby counterfactual worlds play an indispensable dynamical role) in the ion channels of neural networks. As with the brain’s susceptibility to noise, it is argued that in situations where quantum physics plays a role in the brain, it does so for reasons of energy efficiency. As an illustration of this definition of consciousness, a novel proposal is outlined as to why quantum entanglement appears so counter-intuitive.


2021 ◽  
Vol 1 (12) ◽  
pp. 896-903
Author(s):  
Genta Faesal Atsani ◽  
Zanetha Mauly Ilawanda ◽  
Ilma Fahira Basyir

Neural tube defects (NTD) are one of the birth defects or congenital abnormalities that occur in the brain and spine, and commonly find in newborns worldwide. Anencephaly and spina bifida are the two prevalent forms of NTD. The incidence of spina bifida happen on average 1 in 1000 cases of birth worldwide and there are 140,000 cases per year worldwide. Source searches were carried out on the online portal of journal publications as many as 20 sources from MedScape, Google Scholar and the Nation Center for Biotechnology Information / NCBI with the keywords “Neural tube defects (NTD), prevention, and spina bifida”. Spina bifida is a congenital abnormality that occurs in the womb due to a failure of closing process the neural tube during the first few weeks of embryonic development which causes the spine not completely close around the developing spinal cord nerves. NTD can ensue multifactorial conditions such as genetic, environmental, and folate deficiency. The use of folic acid supplementation starting at least 3 months before pregnancy, those are 400 mcg (0.4 mg) per day and 800 mcg per day during pregnancy can reduce the risk of developing neural tube defects such as spina bifida. Generally, spina bifida is undertaking by surgery and the regulation of patients comorbid. Public can find out prevention to avoid or reduce the risk of spina bifida so that the incidence of spina bifida can decrease along with the increasing awareness of the community regarding this disease.


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