Cell fate specification in an in vitro model of neural development

1998 ◽  
Vol 76 (1) ◽  
pp. 63-76 ◽  
Author(s):  
Ruth Jostock ◽  
Martin Rentrop ◽  
Alfred Maelicke
Keyword(s):  
Cell Fate ◽  
Neural Development ◽  
In Vitro Model ◽  
Cell Fate Specification ◽  
Fate Specification ◽  
Vitro Model

scholarly journals Making sense of neural development by comparing wiring strategies for seeing and hearing

Science ◽  
2021 ◽  
Vol 371 (6525) ◽  
pp. eaaz6317
Author(s):  
A. A. Sitko ◽  
L. V. Goodrich
Keyword(s):  
Cell Fate ◽  
Neural Development ◽  
Neural Circuits ◽  
Cell Fate Specification ◽  
Fate Specification ◽  
Making Sense ◽  
The World ◽  
Activity Dependent

The ability to perceive and interact with the world depends on a diverse array of neural circuits specialized for carrying out specific computations. Each circuit is assembled using a relatively limited number of molecules and common developmental steps, from cell fate specification to activity-dependent synaptic refinement. Given this shared toolkit, how do individual circuits acquire their characteristic properties? We explore this question by comparing development of the circuitry for seeing and hearing, highlighting a few examples where differences in each system’s sensory demands necessitate different developmental strategies.

scholarly journals Temporal cell fate determination in the spinal cord is mediated by the duration of Notch signalling

2021 ◽  
Author(s):  
Craig T Jacobs ◽  
Aarti Kejriwal ◽  
Katrinka M Kocha ◽  
Kevin Y Jin ◽  
Peng Huang
Keyword(s):  
Spinal Cord ◽  
Cell Fate ◽  
Neural Development ◽  
Time Windows ◽  
Notch Signalling ◽  
Cell Fate Specification ◽  
Temporal Regulation ◽  
Fate Specification ◽  
Temporal Differentiation ◽  
High Level

During neural development, progenitor cells generate different types of neurons in specific time windows. Despite the characterisation of many of the transcription factor networks involved in these differentiation events, the mechanism behind their temporal regulation is poorly understood. To address this question, we studied the temporal differentiation of the simple lateral floor plate (LFP) domain in the zebrafish spinal cord. LFP progenitors sequentially generate early-born Kolmer-Agduhr″ (KA″) interneurons and late-born V3 interneurons. Analysis using a Notch signalling reporter demonstrates that these cell populations have distinct Notch signalling profiles. Not only do V3 cells receive higher total levels of Notch response, but they collect this response over a longer duration compared to V3 cells. To test whether the duration of Notch signalling determines the temporal cell fate specification, we combined a transgene that constitutively activates Notch signalling in the ventral spinal cord with a heat shock inducible Notch signalling terminator to switch off Notch response at any given time. Sustained Notch signalling results in expanded LFP progenitors while KA″ and V3 interneurons fail to specify. Early termination of Notch signalling leads to exclusively KA″ cell fate, despite the high level of Notch signalling, whereas late attenuation of Notch signalling drives only V3 cell fate. This suggests that the duration of Notch signalling is instructive in cell fate specification. Interestingly, knockdown experiments reveal a role for the Notch ligand Jag2b in maintaining LFP progenitors and limiting their differentiation into KA″ and V3 cells. Our results indicate that Notch signalling is required for neural progenitor maintenance while a specific attenuation timetable defines the fate of the postmitotic progeny.

scholarly journals cnd-1/NeuroD1 Functions with the Homeobox Gene ceh-5/Vax2 and Hox Gene ceh-13/labial To Specify Aspects of RME and DD Neuron Fate in Caenorhabditis elegans

2020 ◽  
Vol 10 (9) ◽  
pp. 3071-3085
Author(s):  
Wendy Aquino-Nunez ◽  
Zachery E Mielko ◽  
Trae Dunn ◽  
Elise M Santorella ◽  
Ciara Hosea ◽  
...  
Keyword(s):  
Nervous System ◽  
Transcription Factor ◽  
Caenorhabditis Elegans ◽  
Cell Fate ◽  
Neural Development ◽  
Nervous System Development ◽  
Cell Fate Specification ◽  
Hox Gene ◽  
Fate Specification

Abstract Identifying the mechanisms behind neuronal fate specification are key to understanding normal neural development in addition to neurodevelopmental disorders such as autism and schizophrenia. In vivo cell fate specification is difficult to study in vertebrates. However, the nematode Caenorhabditis elegans, with its invariant cell lineage and simple nervous system of 302 neurons, is an ideal organism to explore the earliest stages of neural development. We used a comparative transcriptome approach to examine the role of cnd-1/NeuroD1 in C. elegans nervous system development and function. This basic helix-loop-helix transcription factor is deeply conserved across phyla and plays a crucial role in cell fate specification in both the vertebrate nervous system and pancreas. We find that cnd-1 controls expression of ceh-5, a Vax2-like homeobox class transcription factor, in the RME head motorneurons and PVQ tail interneurons. We also show that cnd-1 functions redundantly with the Hox gene ceh-13/labial in defining the fate of DD1 and DD2 embryonic ventral nerve cord motorneurons. These data highlight the utility of comparative transcriptomes for identifying transcription factor targets and understanding gene regulatory networks.

MicroRNA Profiling as a Tool for Pathway Analysis in a Human In Vitro Model for Neural Development

2012 ◽  
Vol 19 (36) ◽  
pp. 6214-6223 ◽  
Author(s):  
S. Nerini-Molteni ◽  
M. Mennecozzi ◽  
M. Fabbri ◽  
M. G. Sacco ◽  
K. Vojnits ◽  
...  
Keyword(s):  
Pathway Analysis ◽  
Neural Development ◽  
In Vitro Model ◽  
Microrna Profiling ◽  
Vitro Model

MicroRNA Profiling as a Tool for Pathway Analysis in a Human In Vitro Model for Neural Development

2012 ◽  
Vol 19 (36) ◽  
pp. 6214-6223 ◽  
Author(s):  
S. Nerini-Molteni ◽  
M. Mennecozzi ◽  
M. Fabbri ◽  
M. G. Sacco ◽  
K. Vojnits ◽  
...  
Keyword(s):  
Pathway Analysis ◽  
Neural Development ◽  
In Vitro Model ◽  
Microrna Profiling ◽  
Vitro Model

Caenorhabditis elegans lin-25: A Study of Its Role in Multiple Cell Fate Specification Events Involving Ras and the Identification and Characterization of Evolutionarily Conserved Domains

Genetics ◽  
2000 ◽  
Vol 156 (3) ◽  
pp. 1083-1096
Author(s):  
Lars Nilsson ◽  
Teresa Tiensuu ◽  
Simon Tuck
Keyword(s):  
Caenorhabditis Elegans ◽  
Cell Fate ◽  
Nuclear Translocation ◽  
Cell Fate Specification ◽  
Sequence Comparisons ◽  
Vulval Development ◽  
Fate Specification ◽  
C Elegans

Abstract Caenorhabditis elegans lin-25 functions downstream of let-60 ras in the genetic pathway for the induction of the 1° cell fate during vulval development and encodes a novel 130-kD protein. The biochemical activity of LIN-25 is presently unknown, but the protein appears to function together with SUR-2, whose human homologue binds to Mediator, a protein complex required for transcriptional regulation. We describe here experiments that indicate that, besides its role in vulval development, lin-25 also participates in the fate specification of a number of other cells in the worm that are known to require Ras-mediated signaling. We also describe the cloning of a lin-25 orthologue from C. briggsae. Sequence comparisons suggest that the gene is evolving relatively rapidly. By characterizing the molecular lesions associated with 10 lin-25 mutant alleles and by assaying in vivo the activity of mutants lin-25 generated in vitro, we have identified three domains within LIN-25 that are required for activity or stability. We have also identified a sequence that is required for efficient nuclear translocation. We discuss how lin-25 might act in cell fate specification in C. elegans within the context of models for lin-25 function in cell identity and cell signaling.

scholarly journals Evolutionary conservation of a cell fate specification gene: the Hydra achaete-scute homolog has proneural activity in Drosophila

Development ◽  
1995 ◽  
Vol 121 (12) ◽  
pp. 4027-4035 ◽  
Author(s):  
A. Grens ◽  
E. Mason ◽  
J.L. Marsh ◽  
H.R. Bode
Keyword(s):  
Cell Fate ◽  
Sequence Similarity ◽  
Ectopic Expression ◽  
Bhlh Protein ◽  
Amino Acid Sequence Similarity ◽  
Cell Fate Specification ◽  
Fate Specification ◽  
Helix Loop Helix ◽  
Bhlh Genes

Members of the Achaete-scute family of basic helix-loop-helix transcription factors are involved in cell fate specification in vertebrates and invertebrates. We have isolated and characterized a cnidarian achaete-scute homolog, CnASH, from Hydra vulgaris, a representative of an evolutionarily ancient branch of metazoans. There is a single achaete-scute gene in Hydra, and the bHLH domain of the predicted gene product shares a high degree of amino acid sequence similarity with those of vertebrate and Drosophila Achaete-scute proteins. In Hydra, CnASH is expressed in a subset of the interstitial cells as well as differentiation intermediates of the nematocyte pathways. In vitro translated CnASH protein can form heterodimers with the Drosophila bHLH protein Daughterless, and these dimers bind to consensus Achaete-scute DNA binding sites in a sequence-specific manner. Ectopic expression of CnASH in wild-type late third instar Drosophila larvae and early pupae leads to the formation of ectopic sensory organs, mimicking the effect of ectopic expression of the endogenous achaete-scute genes. Expression of CnASH in flies that are achaete and scute double mutants gives partial rescue of the mutant phenotype, comparable to the degree of rescue obtained by ectopic expression of the Drosophila genes. These results indicate that the achaete-scute type of bHLH genes for cell fate specification, as well as their mode of action, arose early and have been conserved during metazoan evolution.

An in vitro model for investigation of vitamin A effects on wound healing

2021 ◽  
pp. 1-6
Author(s):  
Hoda Keshmiri Neghab ◽  
Mohammad Hasan Soheilifar ◽  
Gholamreza Esmaeeli Djavid
Keyword(s):  
Wound Healing ◽  
Endothelial Cell ◽  
Vitamin A ◽  
In Vitro Model ◽  
Cellular Proliferation ◽  
Endothelial Cell Migration ◽  
Normal Fibroblast ◽  
Anti Inflammatory ◽  
Vitro Model

Abstract. Wound healing consists of a series of highly orderly overlapping processes characterized by hemostasis, inflammation, proliferation, and remodeling. Prolongation or interruption in each phase can lead to delayed wound healing or a non-healing chronic wound. Vitamin A is a crucial nutrient that is most beneficial for the health of the skin. The present study was undertaken to determine the effect of vitamin A on regeneration, angiogenesis, and inflammation characteristics in an in vitro model system during wound healing. For this purpose, mouse skin normal fibroblast (L929), human umbilical vein endothelial cell (HUVEC), and monocyte/macrophage-like cell line (RAW 264.7) were considered to evaluate proliferation, angiogenesis, and anti-inflammatory responses, respectively. Vitamin A (0.1–5 μM) increased cellular proliferation of L929 and HUVEC (p < 0.05). Similarly, it stimulated angiogenesis by promoting endothelial cell migration up to approximately 4 fold and interestingly tube formation up to 8.5 fold (p < 0.01). Furthermore, vitamin A treatment was shown to decrease the level of nitric oxide production in a dose-dependent effect (p < 0.05), exhibiting the anti-inflammatory property of vitamin A in accelerating wound healing. These results may reveal the therapeutic potential of vitamin A in diabetic wound healing by stimulating regeneration, angiogenesis, and anti-inflammation responses.

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