Hes genes regulate sequential stages of neurogenesis in the olfactory epithelium

Development ◽  
2000 ◽  
Vol 127 (11) ◽  
pp. 2323-2332 ◽  
Author(s):  
E. Cau ◽  
G. Gradwohl ◽  
S. Casarosa ◽  
R. Kageyama ◽  
F. Guillemot
Keyword(s):  
Double Mutant ◽  
Neural Progenitor Cells ◽  
Mouse Embryos ◽  
Neural Progenitors ◽  
Regulatory Mechanisms ◽  
Transcriptional Repressors ◽  
Normal Domain ◽  
Proneural Gene ◽  
Bhlh Gene ◽  
Olfactory Placode

We have characterised the functions of the bHLH transcriptional repressors HES1 and HES5 in neurogenesis, using the development of the olfactory placodes in mouse embryos as a model. Hes1 and Hes5 are expressed with distinct patterns in the olfactory placodes and are subject to different regulatory mechanisms. Hes1 is expressed in a broad placodal domain, which is maintained in absence of the neural determination gene Mash1. In contrast, expression of Hes5 is restricted to clusters of neural progenitor cells and requires Mash1 function. Mutations in Hes1 and Hes5 also have distinct consequences on olfactory placode neurogenesis. Loss of Hes1 function leads both to expression of Mash1 outside of the normal domain of neurogenesis and to increased density of MASH1-positive progenitors within this domain, and results in an excess of neurons after a delay. A mutation in Hes5 does not produce any apparent defect. However, olfactory placodes that are double mutant for Hes1 and Hes5 upregulate Ngn1, a neural bHLH gene activated downstream of Mash1, and show a strong and rapid increase in neuronal density. Together, our results suggest that Hes1 regulates Mash1 transcription in the olfactory placode in two different contexts, initially as a prepattern gene defining the placodal domain undergoing neurogenesis and, subsequently, as a neurogenic gene controlling the density of neural progenitors in this domain. Hes5 synergizes with Hes1 and regulates neurogenesis at the level of Ngn1 expression. Therefore, the olfactory sensory neuron lineage is regulated at several steps by negative signals acting through different Hes genes and targeting the expression of different proneural gene homologs.

scholarly journals Temporal and epigenetic regulation of neurodevelopmental plasticity

2007 ◽  
Vol 363 (1489) ◽  
pp. 23-38 ◽  
Author(s):  
Nicholas D Allen
Keyword(s):  
Stem Cells ◽  
Progenitor Cells ◽  
Developmental Plasticity ◽  
Neural Progenitor Cells ◽  
Embryonic Stem ◽  
Neural Progenitor ◽  
Neural Progenitors ◽  
Developmental Potential ◽  
Neural Lineage

The anticipated therapeutic uses of neural stem cells depend on their ability to retain a certain level of developmental plasticity. In particular, cells must respond to developmental manipulations designed to specify precise neural fates. Studies in vivo and in vitro have shown that the developmental potential of neural progenitor cells changes and becomes progressively restricted with time. For in vitro cultured neural progenitors, it is those derived from embryonic stem cells that exhibit the greatest developmental potential. It is clear that both extrinsic and intrinsic mechanisms determine the developmental potential of neural progenitors and that epigenetic, or chromatin structural, changes regulate and coordinate hierarchical changes in fate-determining gene expression. Here, we review the temporal changes in developmental plasticity of neural progenitor cells and discuss the epigenetic mechanisms that underpin these changes. We propose that understanding the processes of epigenetic programming within the neural lineage is likely to lead to the development of more rationale strategies for cell reprogramming that may be used to expand the developmental potential of otherwise restricted progenitor populations.

scholarly journals The Role of Leptin in the Development of the Cerebral Cortex in Mouse Embryos

Endocrinology ◽  
2006 ◽  
Vol 147 (2) ◽  
pp. 647-658 ◽  
Author(s):  
Jun Udagawa ◽  
Ryuju Hashimoto ◽  
Hiroaki Suzuki ◽  
Toshihisa Hatta ◽  
Yusuke Sotomaru ◽  
...  
Keyword(s):  
Neuronal Development ◽  
Mrna Level ◽  
Mouse Embryos ◽  
Neural Progenitors ◽  
Cortical Plate ◽  
High Dose ◽  
Wild Type ◽  
Leptin Receptors ◽  
Astrocyte Differentiation

Leptin is detected in the sera, and leptin receptors are expressed in the cerebrum of mouse embryos, suggesting that leptin plays a role in cerebral development. Compared with the wild type, leptin-deficient (ob/ob) mice had fewer cells at embryonic day (E) 16 and E18 and had fewer 5-bromo-2′-deoxyuridine+ cells at E14 and E16 in the neuroepithelium. Intracerebroventricular leptin injection in E14 ob/ob embryos increased the number of neuroepithelium cells at E16. In cultured neurosphere cells, leptin treatment increased Hes1 mRNA expression and maintained neural progenitors. Astrocyte differentiation was induced by low-dose (0.1 μg/ml) but not high-dose (1 μg/ml) leptin. High-dose leptin decreased Id mRNA and increased Ngn1 mRNA in neurosphere cells. The neuropeptide Y mRNA level in the cortical plate was lower in ob/ob than the wild type at E16 and E18. These results suggest that leptin maintains neural progenitors and is related to glial and neuronal development in embryos.

scholarly journals Lengthening the G1 Phase of Neural Progenitor Cells is Concurrent with An Increase of Symmetric Neuron Generating Division after Stroke

2007 ◽  
Vol 28 (3) ◽  
pp. 602-611 ◽  
Author(s):  
Rui L Zhang ◽  
Zheng G Zhang ◽  
Cynthia Roberts ◽  
Yvonne LeTourneau ◽  
Mei Lu ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cycle Length ◽  
Neural Progenitor Cells ◽  
Neural Progenitors ◽  
Adult Rats ◽  
Neuronal Marker ◽  
Daughter Cells ◽  
P Fraction ◽  
Labeling Scheme ◽  
Cell Cycle Length

The proportion of neural progenitors that remain in ( P fraction) and exit from ( Q fraction) the cell cycle determines the degree of neurogenesis. Using S-phase labeling with 5-bromo-2′-deoxyuridine and a double nucleoside analog-labeling scheme, we measured the cell-cycle kinetics of neural progenitors and estimated the proportion of P and Q fractions in the subventricular zone (SVZ) of adult rats subjected to stroke. Stroke increased SVZ cell proliferation, starting 2 days, reaching a maximum 4 and 7 days after stroke. The cell-cycle length ( TC) of SVZ cells changed dynamically over a period of 2 to 14 days after stroke, with the shortest length of 11 h at 2 days after stroke. The reduction of the TC resulted from a decrease of the G1 phase because the G2, M, and S phases were unchanged. In addition, during this period, reduction of the G1 phase was concomitant with an increase in the P fraction, whereas an augmentation of the Q fraction was associated with lengthening of the G1 phase. Furthermore, approximately 90% of cells that exited the cell cycle were neurons and the population of a pair of dividing daughter cells with a neuronal marker increased from 9% at 2 days to 26% at 14 days after stroke. These data suggest that stroke triggers early expansion of the progenitor pool via shortening the cell-cycle length and retaining daughter cells within the cell cycle, and the lengthening of G1 leads to daughter cells exiting the cell cycle and differentiating into neurons.

scholarly journals The Drosophila Sp8 transcription factor Buttonhead prevents premature differentiation of intermediate neural progenitors

eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Yonggang Xie ◽  
Xiaosu Li ◽  
Xian Zhang ◽  
Shaolin Mei ◽  
Hongyu Li ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Transcription Factor ◽  
Neural Progenitor Cells ◽  
Neural Progenitors ◽  
Homeodomain Protein ◽  
Cell Cycle Exit ◽  
Developmental Potential ◽  
Drosophila Homolog ◽  
Ets Transcription Factor ◽  
Mother Cells

Intermediate neural progenitor cells (INPs) need to avoid differentiation and cell cycle exit while maintaining restricted developmental potential, but mechanisms preventing differentiation and cell cycle exit of INPs are not well understood. In this study, we report that the Drosophila homolog of mammalian Sp8 transcription factor Buttonhead (Btd) prevents premature differentiation and cell cycle exit of INPs in Drosophila larval type II neuroblast (NB) lineages. We show that the loss of Btd leads to elimination of mature INPs due to premature differentiation of INPs into terminally dividing ganglion mother cells. We provide evidence to demonstrate that Btd prevents the premature differentiation by suppressing the expression of the homeodomain protein Prospero in immature INPs. We further show that Btd functions cooperatively with the Ets transcription factor Pointed P1 to promote the generation of INPs. Thus, our work reveals a critical mechanism that prevents premature differentiation and cell cycle exit of Drosophila INPs.

Effects of resveratrol on the differentiation fate of neural progenitor cells of mouse embryos infected with Trypanosoma cruzi

2019 ◽  
Vol 132 ◽  
pp. 156-161 ◽  
Author(s):  
Mateus Fracasso ◽  
Nathieli B. Bottari ◽  
Aniélen D. da Silva ◽  
Thirssa H. Grando ◽  
Micheli M. Pillat ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Progenitor Cells ◽  
Neural Progenitor Cells ◽  
Neural Progenitor ◽  
Mouse Embryos

scholarly journals DOT1L-mediated murine neuronal differentiation associates with H3K79me2 accumulation and preserves SOX2-enhancer accessibility

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Francesco Ferrari ◽  
Laura Arrigoni ◽  
Henriette Franz ◽  
Annalisa Izzo ◽  
Ludmila Butenko ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neuronal Differentiation ◽  
Promoter Region ◽  
Cellular Differentiation ◽  
Neural Progenitor Cells ◽  
Embryonic Stem ◽  
Neural Progenitors ◽  
Murine Embryonic Stem Cells ◽  
Transcriptional State

Abstract During neuronal differentiation, the transcriptional profile and the epigenetic context of neural committed cells is subject to significant rearrangements, but a systematic quantification of global histone modification changes is still missing. Here, we show that H3K79me2 increases and H3K27ac decreases globally during in-vitro neuronal differentiation of murine embryonic stem cells. DOT1L mediates all three degrees of methylation of H3K79 and its enzymatic activity is critical to modulate cellular differentiation and reprogramming. In this context, we find that inhibition of DOT1L in neural progenitor cells biases the transcriptional state towards neuronal differentiation, resulting in transcriptional upregulation of genes marked with H3K27me3 on the promoter region. We further show that DOT1L inhibition affects accessibility of SOX2-bound enhancers and impairs SOX2 binding in neural progenitors. Our work provides evidence that DOT1L activity gates differentiation of progenitors by allowing SOX2-dependent transcription of stemness programs.

scholarly journals A Casz1–NuRD complex regulates temporal identity transitions in neural progenitors

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Pierre Mattar ◽  
Christine Jolicoeur ◽  
Thanh Dang ◽  
Sujay Shah ◽  
Brian S. Clark ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Neural Progenitor Cells ◽  
Neural Progenitors ◽  
Biochemical Process ◽  
Nurd Complex ◽  
Nucleosome Remodeling ◽  
Correct Sequence ◽  
Different Types ◽  
Temporal Identity ◽  
Identity Transitions

AbstractNeural progenitor cells undergo identity transitions during development to ensure the generation different types of neurons and glia in the correct sequence and proportions. A number of temporal identity factors that control these transitions in progenitor competence have been identified, but the molecular mechanisms underlying their function remain unclear. Here, we asked how Casz1, the mammalian orthologue of Drosophila castor, regulates competence during retinal development. We show that Casz1 is required to control the transition between neurogenesis and gliogenesis. Using BioID proteomics, we reveal that Casz1 interacts with the nucleosome remodeling and deacetylase (NuRD) complex in retinal cells. Finally, we show that both the NuRD and the polycomb repressor complexes are required for Casz1 to promote the rod fate and suppress gliogenesis. As additional temporal identity factors have been found to interact with the NuRD complex in other contexts, we propose that these factors might act through this common biochemical process to regulate neurogenesis.

scholarly journals LPA signaling acts as a cell-extrinsic mechanism to initiate cilia disassembly and promote neurogenesis

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Huai-Bin Hu ◽  
Zeng-Qing Song ◽  
Guang-Ping Song ◽  
Sen Li ◽  
Hai-Qing Tu ◽  
...  
Keyword(s):  
Primary Cilia ◽  
Neural Progenitor Cells ◽  
Regulatory Mechanisms ◽  
Systematic Analysis ◽  
Lpa Receptor ◽  
Genetic Inactivation ◽  
Dynamic Assembly ◽  
A Cell ◽  
Extracellular Factor ◽  
Serum Components

AbstractDynamic assembly and disassembly of primary cilia controls embryonic development and tissue homeostasis. Dysregulation of ciliogenesis causes human developmental diseases termed ciliopathies. Cell-intrinsic regulatory mechanisms of cilia disassembly have been well-studied. The extracellular cues controlling cilia disassembly remain elusive, however. Here, we show that lysophosphatidic acid (LPA), a multifunctional bioactive phospholipid, acts as a physiological extracellular factor to initiate cilia disassembly and promote neurogenesis. Through systematic analysis of serum components, we identify a small molecular—LPA as the major driver of cilia disassembly. Genetic inactivation and pharmacological inhibition of LPA receptor 1 (LPAR1) abrogate cilia disassembly triggered by serum. The LPA-LPAR-G-protein pathway promotes the transcription and phosphorylation of cilia disassembly factors-Aurora A, through activating the transcription coactivators YAP/TAZ and calcium/CaM pathway, respectively. Deletion of Lpar1 in mice causes abnormally elongated cilia and decreased proliferation in neural progenitor cells, thereby resulting in defective neurogenesis. Collectively, our findings establish LPA as a physiological initiator of cilia disassembly and suggest targeting the metabolism of LPA and the LPA pathway as potential therapies for diseases with dysfunctional ciliogenesis.

scholarly journals Notch signalling maintains Hedgehog responsiveness via a Gli-dependent mechanism during spinal cord patterning in zebrafish

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Craig T Jacobs ◽  
Peng Huang
Keyword(s):  
Spinal Cord ◽  
Primary Cilia ◽  
Neural Progenitor Cells ◽  
Cell Signalling ◽  
Notch Signalling ◽  
Neural Progenitors ◽  
Loss Of Function ◽  
Dynamic Interactions ◽  
Dependent Mechanism

Spinal cord patterning is orchestrated by multiple cell signalling pathways. Neural progenitors are maintained by Notch signalling, whereas ventral neural fates are specified by Hedgehog (Hh) signalling. However, how dynamic interactions between Notch and Hh signalling drive the precise pattern formation is still unknown. We applied the PHRESH (PHotoconvertible REporter of Signalling History) technique to analyse cell signalling dynamics in vivo during zebrafish spinal cord development. This approach reveals that Notch and Hh signalling display similar spatiotemporal kinetics throughout spinal cord patterning. Notch signalling functions upstream to control Hh response of neural progenitor cells. Using gain- and loss-of-function tools, we demonstrate that this regulation occurs not at the level of upstream regulators or primary cilia, but rather at the level of Gli transcription factors. Our results indicate that Notch signalling maintains Hh responsiveness of neural progenitors via a Gli-dependent mechanism in the spinal cord.

scholarly journals The peptidyl-prolyl isomerases FKBP15-1 and FKBP15-2 negatively regulate lateral root development by repressing a vacuolar invertase in Arabidopsis

2019 ◽  
Author(s):  
Jun Wang ◽  
Wenjie Sun ◽  
Xiuzhen Kong ◽  
Chunyan Zhao ◽  
Jianfu Li ◽  
...  
Keyword(s):  
Root Development ◽  
Lateral Root ◽  
Protein Modification ◽  
Double Mutant ◽  
Regulatory Mechanisms ◽  
Vacuolar Invertase ◽  
Lateral Root Development ◽  
Peptidyl Prolyl Isomerases ◽  
Fk506 Binding Proteins ◽  
Basal Meristem

Abstract Background Lateral root (LR) architecture determines the efficiency of nutrient absorption and anchors the plant. Internal auxin regulatory mechanisms that control the development of LR have been identified, but how external nutrients influence lateral root development remains elusive. Results We have characterized the functions of the FK506-binding proteins FKBP15-1 and FKBP15-2 in Arabidopsis. FKBP genes are mainly expressed in the vascular bundle of the root basal meristem region, and the FKBP proteins are localized to the endoplasmic reticulum. Co-IP and BIFC assays showed that FKBP15-1 and FKBP15-2 interact with the vacuolar invertase 2 (VIN2). Compared to Col-0 and the single mutants, the double mutant fkbp15-1fkbp15-2 had more LRs and LR initiation density, and possessed higher sucrose catalytic activity. Moreover, VIN2 can complement the phenotype of increased LRs in the fkbp15-1fkbp15-2 double mutant. Conclusion Our results indicate that FKBP15-1 and FKBP15-2 together participate in the control of LR numbers by regulating the enzyme activity of VIN2. Due to the activity of peptidylprolyl cis-trans isomerases owned by FKBP family proteins, our results provide a clue to further analysis the interplay between lateral root development and protein modification.

Sign in / Sign up

Export Citation Format

Share Document