Telencephalic Neurogenesis Versus Telencephalic Differentiation of Pluripotent Stem Cells

Nat, Roxana; Apostolova, Galina; Dechant, Georg

doi:10.5772/54251

Cited by 4 publications

(6 citation statements)

References 119 publications

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“…We found a very different pattern in the adult cerebral vesicle, with the ventral-anterior part now devoid of expression ( Fig2G-H and G’ ) and the dorsal half showing expanded expression, thus resembling the situation in vertebrates. This dorsal Pax4/6 domain is no longer associated with the lamellar body, which in adult brains is fragmented into scattered lamellar cells (Wicht and Lacalli 2005), but overlaps the Emx and Lhx2/9 domains, as observed in the developing vertebrate telencephalon (Nat et al, 2013). In this overlapping region Pax4/6 reaches the anterior neural border, in a domain starting just above the neuropore ( Fig2I-J ).…”

Section: Resultsmentioning

confidence: 99%

“…In zebrafish and mouse, the telencephalon is divided into a dorsal (pallial) and a ventral (subpallial) domain characterised by the expression of Pax6 and Nkx2.1 , respectively (Hebert and Fishell, 2008). The ventral limit of Pax6 defines the subpallial-pallial boundary (Tole and Hebert 2013, Cocas et al, 2011, Sugahara et al, 2011) helped by the antagonistic interaction with Nk2.1, essential to establish the correct position of this boundary (Nat et al, 2013). Shh is expressed in a ventromedial domain partially overlapping Nkx2.1 (Hebert and Fishell, 2008; Sugahara et al, 2016).…”

Section: Resultsmentioning

confidence: 99%

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

Benito‐Gutiérrez

Stemmer

et al. 2018

Preprint

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The 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.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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

Benito‐Gutiérrez

Stemmer

et al. 2018

Preprint

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“… 48 ) in control and expression of ventral determinates, such as PAX2 and NKX2-1 (basal forebrain progenitors 49 ), involved in formation of the medial ganglionic eminence and GABAergic interneuron differentiation 50 in BP neurons suggest that neuronal identity is altered, as mutual inhibition between PAX6 and NKX2-1 determines dorsal/ventral boundaries in the telencephalon. 51 …”

Section: Resultsmentioning

confidence: 99%

“…These results support the concept that many complex, neuropsychiatric disorders that are identified later in life, including BP, 61 , 62 , 63 may result from alterations in neural differentiation that occur during development. BP neurons expressed transcripts involved in the differentiation of ventral neuronal subtypes, including FOXP2 and NKX2-1 , the hallmark of the medial ganglionic eminence, 51 whereas controls expressed higher levels of factors that confer (or maintain) dorsal telencephalic neuronal identity, including EMX2 , PAX6 , TBR2 , TCF3 and ZNF536 . As telencephalic neurons are involved in a number of neurodegenerative (Huntington's disease and Alzheimer's disease) and neurodevelopmental conditions (autism spectrum disorder, schizophrenia, BP and Rett syndrome), alterations in subtype specification may begin to explain the origin or susceptibility to these conditions.…”

Section: Discussionmentioning

confidence: 99%

Transcripts involved in calcium signaling and telencephalic neuronal fate are altered in induced pluripotent stem cells from bipolar disorder patients

et al. 2014

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Bipolar disorder (BP) is a chronic psychiatric condition characterized by dynamic, pathological mood fluctuations from mania to depression. To date, a major challenge in studying human neuropsychiatric conditions such as BP has been limited access to viable central nervous system tissue to examine disease progression. Patient-derived induced pluripotent stem cells (iPSCs) now offer an opportunity to analyze the full compliment of neural tissues and the prospect of identifying novel disease mechanisms. We have examined changes in gene expression as iPSC derived from well-characterized patients differentiate into neurons; there was little difference in the transcriptome of iPSC, but BP neurons were significantly different than controls in their transcriptional profile. Expression of transcripts for membrane bound receptors and ion channels was significantly increased in BP-derived neurons compared with controls, and we found that lithium pretreatment of BP neurons significantly altered their calcium transient and wave amplitude. The expression of transcription factors involved in the specification of telencephalic neuronal identity was also altered. Control neurons expressed transcripts that confer dorsal telencephalic fate, whereas BP neurons expressed genes involved in the differentiation of ventral (medial ganglionic eminence) regions. Cells were responsive to dorsal/ventral patterning cues, as addition of the Hedgehog (ventral) pathway activator purmorphamine or a dorsalizing agent (lithium) stimulated expression of NKX2-1 (ventral identity) or EMX2 (dorsal) in both groups. Cell-based models should have a significant impact on our understanding of the genesis and therefore treatment of BP; the iPSC cell lines themselves provide an important resource for comparison with other neurodevelopmental disorders.

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“…To this aim, we serially sectioned whole amphioxus heads and reconstructed each of the patterns obtained by stitching multidimensional image datasets. We then focused on the expression analysis of genes orthologous to the major vertebrate telencephalic specification genes FoxG1, Emx and Lhx2; of the anterior forebrain marker Fezf [27]; and of dorsoventral regionalisation factors Pax6 and Nkx2 [28][29][30]. In addition, we looked at the expression of the amphioxus Hedgehog ligand, whose vertebrate counterpart plays a crucial role in telencephalic induction.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2021

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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.

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Telencephalic Neurogenesis Versus Telencephalic Differentiation of Pluripotent Stem Cells

Cited by 4 publications

References 119 publications

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

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

Transcripts involved in calcium signaling and telencephalic neuronal fate are altered in induced pluripotent stem cells from bipolar disorder patients

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

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