Integrative genomic analysis of early neurogenesis reveals a temporal genetic program for differentiation and specification of preplate and Cajal-Retzius neurons

Li, Jia; Sun, Lei; Peng, Xue-Liang; Yu, Xiaoming; Qi, Shao-Jun; Lu, Zhi John; Han, Jing‐Dong J.; Shen, Qin

doi:10.1101/331900

Cited by 3 publications

(4 citation statements)

References 73 publications

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“…We previously performed RNA sequencing (RNA-seq) analysis of cortical NSPCs from the Ebf2-EGFP mouse embryos (Figure 1A)(Chuang et al, 2011; Li et al, 2019a). Among the genes that are differentially expressed in E11.5 cortical NSPCs (with the expression level of FPKM > 1 and fold change > 2 compared with that in the preplate neurons), we identified 25 NSPC-enriched lncRNAs (Figure 1A).…”

Section: Resultsmentioning

confidence: 99%

Self-balanced regulation by the long non-coding RNALockdon the cell cycle progression of cortical neural progenitor cells through counteractingcisandtransroles

Qi,

Zheng,

Shen

2024

Preprint

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Neural stem/progenitor cells (NSPCs) undergo active proliferation and exit the cell cycle upon precise regulation to produce differentiated progenies in order. Long noncoding RNAs (lncRNAs) have emerged as critical players in the developmental processes of NSPCs; however, relatively few have been shown to regulate the cell cycle in vivo directly. Here, we identified an NSPC expressed lncRNA Lockd (lncRNA downstream of Cdkn1b) in the developing forebrain. Using in vivo loss of function models by premature termination of Lockd transcription via knockin polyadenylation signals or shRNA-mediated knockdown of Lockd (Lockd-KD), we show that Lockd is required for proper cell cycle progression of cortical NSPCs and the production of TBR2+ intermediate neural progenitor cells during cortical development. Interestingly, a comparison of genetic profiling in the two models reveals that Lockd promotes the expression of two counteracting cell cycle-related genes, Cdkn1b in cis and Ccnd1 in trans. Overexpression of Ccnd1 or Cdkn1b-KD can rescue the cellular phenotypes of reduced cycling progenitors in Lockd-KD. Our results imply that lncRNA could act through distinct cis and trans mechanisms to achieve a self-balanced function.

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Section: Resultsmentioning

confidence: 99%

Self-balanced regulation by the long non-coding RNALockdon the cell cycle progression of cortical neural progenitor cells through counteractingcisandtransroles

Qi,

Zheng,

Shen

2024

Preprint

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“…An unexpected feature is that the transcriptome of the β-catenin GOF ChP has some components that fit with a CR cell-like profile, such as Ebf2, Jph3, Reelin, Slit1 53 and others that fit with a medial cortical/hippocampal-like profile (Lef1, Prox1, Wif1), in addition to an array of cortical neuroepithelial or postmitotic neuronal markers (Supplementary Table 1). While it is not possible to delineate whether there is a heterogenous population of CR-like, hippocampal-like, and cortical neuron/neuronal progenitor-like cells in the β-catenin GOF ChP using bulk RNAseq, it appears that the overall picture is one of mixed transcriptomic signatures, at least at a population level.…”

Section: Discussionmentioning

confidence: 99%

Constitutive activation of canonical Wnt signaling disrupts choroid plexus epithelial fate

Parichha

Suresh

Chatterjee

et al. 2020

Preprint

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The choroid plexus (CP) secretes cerebrospinal fluid and is critical for the development and function of the brain. In the telencephalon, the CP epithelium (CPe) arises from the Wnt- and Bmp- expressing cortical hem. We examined the role of canonical Wnt signaling in CPe development and report that the mouse and human embryonic CPe expresses molecules in this pathway. Either loss of function or constitutive activation of β-catenin, a key mediator of canonical Wnt signaling, causes a profound disruption of mouse CPe development. Loss of β-catenin results in a dysmorphic CPe, while constitutive activation of β-catenin causes a loss of CPe identity and a transformation of this tissue to a hippocampal-like identity. Aspects of this phenomenon are recapitulated in human embryonic stem cell (hESC)-derived organoids. Our results indicate that canonical Wnt signaling is required in a precisely regulated manner for normal CP development in the mammalian brain.

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“…Having observed CR cell abnormalities in Lmx1a mutants (Fig. 2D-E'), we studied whether our newly identified Lmx1a downstream targets include genes associated with CR cells, taking advantage of recently identified datasets of genes enriched in CR cells (Franzén et al, 2019;Li et al, 2021). 11 known CR cell-enriched genes were downregulated (Car10,Lhx1,Trp73,Cntnap2,Reln,Cdkn1a,Chst8,Spock1,Akap6,Cacna2d2,Tbr2) and six -were upregulated (Tmem163,Sema6a,Lhx5,Lingo1,Edil3,MAPK8) in the CH of Lmx1a-/-embryos (green dots in Fig.…”

Section: Reduced Exit Of Ch Progenitors From the Cell Cycle And Compr...mentioning

confidence: 99%

“…1K-M): the first segment (labeled as DMS) was between the DNe and FDJ, the second was along the surface of the FDJ, and the third was in the DG (Cai et al, 2018). (Franzén et al, 2019;Li et al, 2021) are shown in green; the only previously identified Lmx1a target in the CH, Cux2 (Fregoso et al, 2019), is shown in red.…”

Section: Lmx1a Protein)mentioning

confidence: 99%

Lmx1a is a master regulator of the cortical hem

Iskusnykh

Fattakhov

et al. 2022

Preprint

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Development of the nervous system depends on signaling centers – specialized cellular populations that produce secreted molecules to regulate neurogenesis in the neighboring neuroepithelium. Some signaling centers also generate key types of neurons. The formation of a signaling center involves its induction, the maintenance of expression of its secreted molecules, and cell differentiation and migration events. How these distinct processes are coordinated during signaling center development remains unknown. Here we show that Lmx1a acts as a master regulator to orchestrate the formation and function of the cortical hem (CH), a critical signaling center that controls hippocampus development. Lmx1a co-regulates CH induction, its Wnt signaling, and the differentiation and migration of CH-derived Cajal-Retzius neurons. Combining RNAseq, genetic, and rescue experiments, we identified major downstream genes that mediate distinct Lmx1a-dependent processes. Our work revealed that signaling centers in the mammalian brain employ master regulatory genes and established a framework for analyzing signaling center development.

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Integrative genomic analysis of early neurogenesis reveals a temporal genetic program for differentiation and specification of preplate and Cajal-Retzius neurons

Abstract: 28Background: Neurogenesis in the developing cerebral cortex begins with the generation of the 29

Cited by 3 publications

References 73 publications

Self-balanced regulation by the long non-coding RNALockdon the cell cycle progression of cortical neural progenitor cells through counteractingcisandtransroles

Self-balanced regulation by the long non-coding RNALockdon the cell cycle progression of cortical neural progenitor cells through counteractingcisandtransroles

Constitutive activation of canonical Wnt signaling disrupts choroid plexus epithelial fate

Lmx1a is a master regulator of the cortical hem

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