Proneural genes and the specification of neural cell types

Bertrand, Nicolas; Castro, Diogo S.; Guillemot, François

doi:10.1038/nrn874

Cited by 1,373 publications

(1,396 citation statements)

References 158 publications

Supporting

Mentioning

1,316

Contrasting

Unclassified

Order By: Relevance

“…The idea that the growth of a new cerebellar lobule is the result of adult neurogenesis was further supported by the expression patterns of Mash1 and Ngn2, markers specific for NPCs 46, 47. Mash1 is predominantly expressed at the tip of the growing lobule, overlapping with CB expression (Fig.…”

Section: Resultsmentioning

confidence: 88%

Peripheral nerve injury induces adult brain neurogenesis and remodelling

Rusanescu

Mao

2016

J Cellular Molecular Medi

View full text Add to dashboard Cite

Unilateral peripheral nerve chronic constriction injury (CCI) has been widely used as a research model of human neuropathic pain. Recently, CCI has been shown to induce spinal cord adult neurogenesis, which may contribute to the chronic increase in nociceptive sensitivity. Here, we show that CCI also induces rapid and profound asymmetrical anatomical rearrangements in the adult rodent cerebellum and pons. This remodelling occurs throughout the hindbrain, and in addition to regions involved in pain processing, also affects other sensory modalities. We demonstrate that these anatomical changes, partially reversible in the long term, result from adult neurogenesis. Neurogenic markers Mash1, Ngn2, doublecortin and Notch3 are widely expressed in the rodent cerebellum and pons, both under normal and injured conditions. CCI‐induced hindbrain structural plasticity is absent in Notch3 knockout mice, a strain with impaired neuronal differentiation, demonstrating its dependence on adult neurogenesis. Grey matter and white matter structural changes in human brain, as a result of pain, injury or learned behaviours have been previously detected using non‐invasive neuroimaging techniques. Because neurogenesis‐mediated structural plasticity is thought to be restricted to the hippocampus and the subventricular zone, such anatomical rearrangements in other parts of the brain have been thought to result from neuronal plasticity or glial hypertrophy. Our findings suggest the presence of extensive neurogenesis‐based structural plasticity in the adult mammalian brain, which may maintain a memory of basal sensory levels, and act as an adaptive mechanism to changes in sensory inputs.

show abstract

Section: Resultsmentioning

confidence: 88%

Peripheral nerve injury induces adult brain neurogenesis and remodelling

Rusanescu

Mao

2016

J Cellular Molecular Medi

View full text Add to dashboard Cite

show abstract

“…The activity of Cath6 to inhibit neuronal differentiation was unexpected because all of the Atonal superfamily molecules thus far identified promote neuronal differentiation (Yan and Wang, 1998;Morrow et al, 1999;Perron et al, 1999;Tomita et al, 2000;Hutcheson and Vetter, 2001;Inoue et al, 2002) and act as transcriptional activators (Cabrera and Alonso, 1991;Johnson et al, 1992;Bertrand et al, 2002). We speculated that Cath6 might function as a transcriptional repressor to counteract the function of these Atonal family genes, although Cath6 did not display significant sequence similarities to known transcriptional repressors.…”

Section: Cath6 Functions As a Transcriptional Activatormentioning

confidence: 86%

“…3E). On the other hand, mutant Cath6 (Cath6 Dbasic) lacking the basic region of bHLH domain, which is required for its DNA-binding activity (Bertrand et al, 2002), did not decrease the ratio of Islet1-positive cells (Fig. 3E).…”

Section: Cath6 Inhibits Differentiation Of the Retinal Ganglion Cellsmentioning

confidence: 95%

Cath6, a bHLH atonal family proneural gene, negatively regulates neuronal differentiation in the retina

Kubo

Nakagawa

2010

Developmental Dynamics

View full text Add to dashboard Cite

Basic helix-loop-helix (bHLH) transcription factors play important roles in cell type specification and differentiation during the development of the nervous system. In this study, we identified a chicken homolog of Atonal 8/ath6 (Cath6) and examined its role in the developing retina. Unlike other Atonal-family proneural genes that induce neuronal differentiation, Cath6 was expressed in stem cell-like progenitor cells in the marginal region of the retina, and its overexpression inhibited neuronal differentiation. A Cath6 fused with a VP16 transactivation domain recapitulated the inhibitory effect of Cath6 on neuronal differentiation, indicating that Cath6 functions as a transcription activator. These results demonstrate that Cath6 constitutes a unique member of the Atonal-family of genes in that it acts as a negative regulator of neuronal differentiation. Developmental Dynamics 239:2492-2500,

show abstract

“…During brain development, NEUROG2 has a specific spatiotemporal expression pattern, because it is exclusively detected in the ventricular zone and only during neurogenesis (Fig 5A) 25. It has been demonstrated that a negative feedback mechanism is essential for the correct transition between the inhibition of neurogenesis and the induction of early gliogenesis 26. Furthermore, the disruption of proneuronal gene activity, such as that of NEUROG2 , may result in loss of commitment in specific neural progenitor cells27 and the generation of ectopic neurons 28.…”

Section: Discussionmentioning

confidence: 99%

Dysregulation of NEUROG2 plays a key role in focal cortical dysplasia

Avansini

Torres

Vieira

et al. 2018

Annals of Neurology

View full text Add to dashboard Cite

ObjectiveFocal cortical dysplasias (FCDs) are an important cause of drug‐resistant epilepsy. In this work, we aimed to investigate whether abnormal gene regulation, mediated by microRNA, could be involved in FCD type II.MethodsWe used total RNA from the brain tissue of 16 patients with FCD type II and 28 controls. MicroRNA expression was initially assessed by microarray. Quantitative polymerase chain reaction, in situ hybridization, luciferase reporter assays, and deep sequencing for genes in the mTOR pathway were performed to validate and further explore our initial study.Resultshsa‐let‐7f (p = 0.039), hsa‐miR‐31 (p = 0.0078), and hsa‐miR34a (p = 0.021) were downregulated in FCD type II, whereas a transcription factor involved in neuronal and glial fate specification, NEUROG2 (p < 0.05), was upregulated. We also found that the RND2 gene, a NEUROG2‐target, is upregulated (p < 0.001). In vitro experiments showed that hsa‐miR‐34a downregulates NEUROG2 by binding to its 5′‐untranslated region. Moreover, we observed strong nuclear expression of NEUROG2 in balloon cells and dysmorphic neurons and found that 28.5% of our patients presented brain somatic mutations in genes of the mTOR pathway.InterpretationOur findings suggest a new molecular mechanism, in which NEUROG2 has a pivotal and central role in the pathogenesis of FCD type II. In this way, we found that the downregulation of hsa‐miR‐34a leads to upregulation of NEUROG2, and consequently to overexpression of the RND2 gene. These findings indicate that a faulty coupling in neuronal differentiation and migration mechanisms may explain the presence of aberrant cells and complete dyslamination in FCD type II. Ann Neurol 2018;83:623–635

show abstract

Proneural genes and the specification of neural cell types

Cited by 1,373 publications

References 158 publications

Peripheral nerve injury induces adult brain neurogenesis and remodelling

Peripheral nerve injury induces adult brain neurogenesis and remodelling

Cath6, a bHLH atonal family proneural gene, negatively regulates neuronal differentiation in the retina

Dysregulation of NEUROG2 plays a key role in focal cortical dysplasia

Contact Info

Product

Resources

About