scholarly journals The dorsoanterior brain of adult amphioxus shares similarities in expression profile and neuronal composition with the vertebrate telencephalon

BMC Biology ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Èlia Benito-Gutiérrez ◽  
Giacomo Gattoni ◽  
Manuel Stemmer ◽  
Silvia D. Rohr ◽  
Laura N. Schuhmacher ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Dopaminergic Neurons ◽  
Ventricular Zone ◽  
Anterior Part ◽  
Brain Regions ◽  
Specific Pattern ◽  
Vertebrate Brain ◽  
Neuronal Progenitors ◽  
Brain Parts ◽  
Combinatorial Expression

Abstract Background The evolutionary origin of the telencephalon, the most anterior part of the vertebrate brain, remains obscure. Since no obvious counterpart to the telencephalon has yet been identified in invertebrate chordates, it is difficult to trace telencephalic origins. One way to identify homologous brain parts between distantly related animal groups is to focus on the combinatorial expression of conserved regionalisation genes that specify brain regions. Results Here, we report the combined expression of conserved transcription factors known to specify the telencephalon in the vertebrates in the chordate amphioxus. Focusing on adult specimens, we detect specific co-expression of these factors in the dorsal part of the anterior brain vesicle, which we refer to as Pars anterodorsalis (PAD). As in vertebrates, expression of the transcription factors FoxG1, Emx and Lhx2/9 overlaps that of Pax4/6 dorsally and of Nkx2.1 ventrally, where we also detect expression of the Hedgehog ligand. This specific pattern of co-expression is not observed prior to metamorphosis. Similar to the vertebrate telencephalon, the amphioxus PAD is characterised by the presence of GABAergic neurons and dorsal accumulations of glutamatergic as well as dopaminergic neurons. We also observe sustained proliferation of neuronal progenitors at the ventricular zone of the amphioxus brain vesicle, as observed in the vertebrate brain. Conclusions Our findings suggest that the PAD in the adult amphioxus brain vesicle and the vertebrate telencephalon evolved from the same brain precursor region in ancestral chordates, which would imply homology of these structures. Our comparative data also indicate that this ancestral brain already contained GABA-, glutamatergic and dopaminergic neurons, as is characteristic for the olfactory bulb of the vertebrate telencephalon. We further speculate that the telencephalon might have evolved in vertebrates via a heterochronic shift in developmental timing.

scholarly journals Regulation of Social Stress and Neural Degeneration by Activity-Regulated Genes and Epigenetic Mechanisms in Dopaminergic Neurons

2020 ◽  
Vol 57 (11) ◽  
pp. 4500-4510
Author(s):  
Clement Kent ◽  
Pavan Agrawal
Keyword(s):  
Transcription Factors ◽  
Neurodegenerative Disorders ◽  
Dopaminergic Neurons ◽  
Social Stress ◽  
Social Deprivation ◽  
Specific Pattern ◽  
Gene Promoters ◽  
Stress Injury ◽  
Epigenetic Marks ◽  
Small Set

Abstract Transcriptional and epigenetic regulation of both dopaminergic neurons and their accompanying glial cells is of great interest in the search for therapies for neurodegenerative disorders such as Parkinson’s disease (PD). In this review, we collate transcriptional and epigenetic changes identified in adult Drosophila melanogaster dopaminergic neurons in response to either prolonged social deprivation or social enrichment, and compare them with changes identified in mammalian dopaminergic neurons during normal development, stress, injury, and neurodegeneration. Surprisingly, a small set of activity-regulated genes (ARG) encoding transcription factors, and a specific pattern of epigenetic marks on gene promoters, are conserved in dopaminergic neurons over the long evolutionary period between mammals and insects. In addition to their classical function as immediate early genes to mark acute neuronal activity, these ARG transcription factors are repurposed in both insects and mammals to respond to chronic perturbations such as social enrichment, social stress, nerve injury, and neurodegeneration. We suggest that these ARG transcription factors and epigenetic marks may represent important targets for future therapeutic intervention strategies in various neurodegenerative disorders including PD.

scholarly journals The potential role of neuroinflammation and transcription factors in Parkinson disease

2017 ◽  
Vol 19 (1) ◽  
pp. 71-80 ◽  
Keyword(s):  
Oxidative Stress ◽  
Transcription Factors ◽  
Substantia Nigra ◽  
Parkinson Disease ◽  
Signaling Pathways ◽  
Dopaminergic Neurons ◽  
Neurodegenerative Disorder ◽  
Brain Regions ◽  
Death Domain

Parkinson disease (PD) is a neurodegenerative disorder characterized by dopaminergic neurons affected by inflammatory processes. Post-mortem analyses of brain and cerebrospinal fluid from PD patients show the accumulation of proinflammatory cytokines, confirming an ongoing neuroinflammation in the affected brain regions. These inflammatory mediators may activate transcription factors—notably nuclear factor κB, Ying-Yang 1 (YY1), fibroblast growth factor 20 (FGF20), and mammalian target of rapamycin (mTOR)—which then regulate downstream signaling pathways that in turn promote death of dopaminergic neurons through death domain-containing receptors. Dopaminergic neurons are vulnerable to oxidative stress and inflammatory attack. An increased level of inducible nitric oxide synthase observed in the substantia nigra and striatum of PD patients suggests that both cytokine—and chemokine-induced toxicity and inflammation lead to oxidative stress that contributes to degeneration of dopaminergic neurons and to disease progression. Lipopolysaccharide activation of microglia in the proximity of dopaminergic neurons in the substantia nigra causes their degeneration, and this appears to be a selective vulnerability of dopaminergic neurons to inflammation. In this review, we will look at the role of various transcription factors and signaling pathways in the development of PD.

scholarly journals Patterning of a telencephalon-like region in the adult brain of amphioxus

2018 ◽  
Author(s):  
Èlia Benito-Gutiérrez ◽  
Manuel Stemmer ◽  
Silvia D Rohr ◽  
Laura N Schuhmacher ◽  
Jocelyn Tang ◽  
...  
Keyword(s):  
Ventricular Zone ◽  
Brain Evolution ◽  
Adult Brain ◽  
Evolutionary Origin ◽  
Embryonic Brain ◽  
Neuronal Progenitors ◽  
Neuronal Types ◽  
The Brain ◽  
Brain Parts ◽  
Invertebrate Chordate

ABSTRACTThe evolutionary origin of the vertebrate telencephalon remains unsolved. A major challenge has been the identification of homologous brain parts in invertebrate chordates. Here we report evidence for a telencephalic region in the brain of amphioxus, the most basally branching invertebrate chordate. This region is characterised, like its vertebrate counterpart, by the combined expression of the telencephalic markers FoxG1, Emx and Lhx2/9. It is located at the anterior neural border and dorsal-ventrally patterned, as in vertebrates, by the antagonistic expression of Pax4/6 and Nkx2.1, and a ventral Hh signal. This part of the brain develops only after metamorphosis via sustained proliferation of neuronal progenitors at the ventricular zone. This is concomitant with a massive expansion of late differentiating neuronal types as revealed by neuropeptide and neurotransmitter profiling. Overall, our results suggest that the adult amphioxus brain shows remarkable similarities to the vertebrate embryonic brain, thus providing a key missing link in understanding the invertebrate-to-vertebrate transition in chordate brain evolution.

scholarly journals Combinatorial programming of human neuronal progenitors using magnetically-guided stoichiometric mRNA delivery

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Sayyed M Azimi ◽  
Steven D Sheridan ◽  
Mostafa Ghannad-Rezaie ◽  
Peter M Eimon ◽  
Mehmet Fatih Yanik
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Progenitor Cells ◽  
Dopaminergic Neurons ◽  
Neural Progenitor Cells ◽  
Expression Patterns ◽  
Neural Progenitor ◽  
Dynamically Reconfigurable ◽  
Neuronal Progenitors ◽  
Copy Numbers

Identification of optimal transcription factor expression patterns to direct cellular differentiation along a desired pathway presents significant challenges. We demonstrate massively combinatorial screening of temporally-varying mRNA transcription factors to direct differentiation of neural progenitor cells using a dynamically-reconfigurable magnetically-guided spotting technology for localizing mRNA, enabling experiments on millimetre size spots. In addition, we present a time-interleaved delivery method that dramatically reduces fluctuations in the delivered transcription factor copy numbers per cell. We screened combinatorial and temporal delivery of a pool of midbrain-specific transcription factors to augment the generation of dopaminergic neurons. We show that the combinatorial delivery of LMX1A, FOXA2 and PITX3 is highly effective in generating dopaminergic neurons from midbrain progenitors. We show that LMX1A significantly increases TH-expression levels when delivered to neural progenitor cells either during proliferation or after induction of neural differentiation, while FOXA2 and PITX3 increase expression only when delivered prior to induction, demonstrating temporal dependence of factor addition.

Interacting functions of snail, twist and huckebein during the early development of germ layers in Drosophila

Development ◽  
1994 ◽  
Vol 120 (5) ◽  
pp. 1137-1150 ◽  
Author(s):  
R. Reuter ◽  
M. Leptin
Keyword(s):  
Transcription Factors ◽  
Digestive Tract ◽  
Early Development ◽  
Target Genes ◽  
Anterior Part ◽  
Posterior Part ◽  
Germ Layers ◽  
Mesoderm Development ◽  
Ventral Furrow

Two zygotic genes, snail (sna) and twist (twi), are required for mesoderm development, which begins with the formation of the ventral furrow. Both twi and sna are expressed ventrally in the blastoderm, encode transcription factors and promote the invagination of the ventral furrow by activating or repressing appropriate target genes. However, sna and twi alone do not define the position of the ventral furrow, since they are also expressed in ventral cells that do not invaginate. We show that huckebein (hkb) sets the anterior and the posterior borders of the ventral furrow, but acts by different modes of regulation. In the posterior part of the blastoderm, hkb represses the expression of sna in the endodermal primordium (which we suggest to be adjacent to the mesodermal primordium). In the anterior part, hkb antagonizes the activation of target genes by twi and sna. Here, bicoid permits the co-expression of hkb, sna and twi, which are all required for the development of the anterior digestive tract. We suggest that mesodermal fate is determined where sna and twi but not hkb are expressed. Anteriorly hkb together with sna determines endodermal fate, and hkb together with sna and twi are required for foregut development.

Hedonic-Specific Activity in Piriform Cortex During Odor Imagery Mimics That During Odor Perception

2007 ◽  
Vol 98 (6) ◽  
pp. 3254-3262 ◽  
Author(s):  
Moustafa Bensafi ◽  
Noam Sobel ◽  
Rehan M. Khan
Keyword(s):  
Specific Activity ◽  
Piriform Cortex ◽  
Brain Regions ◽  
Specific Pattern ◽  
Functional Magnetic Resonance ◽  
Resonance Imaging ◽  
Odor Perception ◽  
Cortical Areas ◽  
Visual Cortical ◽  
Left Insula

Although it is known that visual imagery is accompanied by activity in visual cortical areas, including primary visual cortex, whether olfactory imagery exists remains controversial. Here we asked whether cue-dependent olfactory imagery was similarly accompanied by activity in olfactory cortex, and in particular whether hedonic-specific patterns of activity evident in olfactory perception would also be present during olfactory imagery. We used functional magnetic resonance imaging to measure activity in subjects who alternated between smelling and imagining pleasant and unpleasant odors. Activity induced by imagining odors mimicked that induced by perceiving real odorants, not only in the particular brain regions activated, but also in its hedonic-specific pattern. For both real and imagined odors, unpleasant stimuli induced greater activity than pleasant stimuli in the left frontal portion of piriform cortex and left insula. These findings combine with findings from other modalities to suggest activation of primary sensory cortical structures during mental imagery of sensory events.

scholarly journals Prolonged inhibition of hepatocellular carcinoma cell proliferation by combinatorial expression of defined transcription factors

2018 ◽  
Vol 109 (11) ◽  
pp. 3543-3553 ◽  
Author(s):  
Yasuo Takashima ◽  
Kenichi Horisawa ◽  
Miyako Udono ◽  
Yasuyuki Ohkawa ◽  
Atsushi Suzuki
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Transcription Factors ◽  
Carcinoma Cell ◽  
Hepatocellular Carcinoma Cell ◽  
Combinatorial Expression

scholarly journals Ibogaine Modifies GDNF, BDNF and NGF Expression in Brain Regions Involved in Mesocorticolimbic and Nigral Dopaminergic Circuits

2018 ◽  
Author(s):  
Soledad Marton ◽  
Bruno González ◽  
Sebastián Rodríguez ◽  
Ernesto Miquel ◽  
Laura Martínez Palma ◽  
...  
Keyword(s):  
Neurotrophic Factor ◽  
Dopaminergic Neurons ◽  
Brain Regions ◽  
Dopamine Neurons ◽  
Acute Administration ◽  
Dependent Manner ◽  
Self Administration ◽  
Seeking Behavior ◽  
A Site ◽  
Dose Dependent

<p>Ibogaine is a psychedelic alkaloid which has been subject of intense scientific research due to its reported ability to attenuate drug-seeking behavior. Recent work suggested that ibogaine effects on alcohol self-administration in rats was related to the release of Glial Cell Derived Neurotrophic Factor (GDNF) in the Ventral Tegmental Area (VTA), a mesencephalic region which hosts soma of dopamine neurons. It is well known that neurotrophic factors (NFs) mediate the neuroadaptations induced in the mesocorticolimbic dopaminergic system by repeated exposure to drugs. Although previous reports have shown ibogaine´s ability to induce GDNF expression in rat midbrain, there are no studies addressing its effect on the expression of GDNF, Brain Derived Neurotrophic Factor (BDNF) or Nerve Growth Factor (NGF) in distinct regions containing dopaminergic neurons. In this work, we examined the effect of ibogaine acute administration on the expression of these NFs in the VTA, Prefrontal Cortex (PFC), Nucleus Accumbens (NAcc) and the Substantia Nigra (SN). Thus, rats were i.p. treated with ibogaine 20 mg/kg (I<sub>20</sub>), 40 mg/kg (I<sub>40</sub>) or vehicle, and NFs expression was analyzed after 3 and 24 hours. Only at 24 h an increase of the expression for the three NFs were observed in a site and dose dependent manner. Results for GDNF showed that only I<sub>40</sub> selectively upregulated its expression in the VTA and SN. Both doses of ibogaine elicited a large increase in the expression of BDNF in the NAcc, SN and PFC, while a significant effect was found in the VTA only for I<sub>40</sub>. Finally, NGF was found to be upregulated in all regions after I<sub>40</sub>, while a selective upregulation was found in PFC and VTA for the I<sub>20</sub> treatment. An increase in the content of mature GDNF was observed in the VTA but no significant increase in the mature BDNF protein content was found in all the studied areas. Interestingly, an increase in the content of proBDNF was detected in the NAcc for both treatments. Further research is needed to understand the neurochemical bases of these changes, and to confirm their contribution to the anti-addictive properties of ibogaine. </p>

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