Regulation of downstream neuronal genes by proneural transcription factors during initial neurogenesis in the vertebrate brain

Abstract

BackgroundNeurons arise in very specific regions of the neural tube, controlled by components of the Notch signalling pathway, proneural genes, and other bHLH transcription factors. How these specific neuronal areas in the brain are generated during development is just beginning to be elucidated. Notably, the critical role of proneural genes during differentiation of the neuronal populations that give rise to the early axon scaffold in the developing brain is not understood. The regulation of their downstream effectors remains poorly defined.ResultsThis study provides the first overview of the spatiotemporal expression of proneural genes in the neuronal populations of the early axon scaffold in both chick and mouse. Overexpression studies and mutant mice have identified a number of specific neuronal genes that are targets of proneural transcription factors in these neuronal populations.ConclusionTogether, these results improve our understanding of the molecular mechanisms involved in differentiation of the first neuronal populations in the brain.Electronic supplementary materialThe online version of this article (doi:10.1186/s13064-016-0077-7) contains supplementary material, which is available to authorized users.

Ldb1 and Rnf12-dependent regulation of Lhx2 controls the relative balance between neurogenesis and gliogenesis in retina

“…This indicates that, although Lhx2 is required for both Notch pathway gene expression and Notch-mediated Müller gliogenesis (de Melo et al, 2016a), misexpression of Lhx2 in RPCs can inhibit Notch signaling and promote retinal neurogenesis, similar to the effects of overexpressing Lhx2 in the hippocampus (Subramanian et al, 2011). One mechanism by which this might occur is through Lhx2dependent regulation of the expression of Ascl1 and Neurog2 in RPCs, which, depending on context, can negatively (Hufnagel et al, 2010;Vasconcelos et al, 2016;Ware et al, 2016) or positively (Nelson et al, 2009) regulate Notch signaling in neural progenitors.…”

Disrupted Hypothalamo-Pituitary Axis in Association With Reduced SHH Underlies the Pathogenesis of NOTCH-Deficiency

“…In situ hybridisation All embryos were fixed in 4% PFA/PBS at 4˚C overnight, rinsed and processed for whole-mount RNA in situ hybridisation. Sense and anti-sense probes were generated from plasmids cloned as previously described (24) or plasmids provided as a gift. The protocol for single and double in situ hybridisation has been previously described (23).…”

“…3D, arrow), further observation of the developing forebrain was compromised in these Rbpj knockout embryos as they are dying at this stage from heart failure (30). Therefore, to attempt a rescue of these dying embryos, we used Rbpj L/L ;CreER T2 mice where the activity of the Cre-recombinase could be induced at a specific time point during pregnancy using tamoxifen (24). Rbpj L/L excision was fully efficient 12 hours after the tamoxifen injection ( Fig.…”

“…How NOTCH signalling contributes to maintaining Shh expression in the AH during this period is not yet defined. However, we know that NOTCH signalling pathway plays a key role in cell fate choice during AH neurogenesis (23,24) in balancing the number of progenitors cells with that of differentiating neurons (57). Our previous studies show that transient inhibition of NOTCH signalling during early hypothalamic development enhances neurogenesis in the AH.…”

“…This complex is then capable of transcriptional regulation (22). Early in development, NOTCH is implicated in the correct patterning of the first neuronal population of the developing hypothalamus (23,24). Colocalisation of SHH activity and NOTCH components, such as Dll1 and Hes5, in both chick and mouse embryos is present at the level of the developing ventral forebrain corresponding to the hypothalamus primordium (23)(24)(25).…”