scholarly journals Toward a More Accurate 3D Atlas of C. elegans Neurons

2021 ◽  
Author(s):  
MICHAEL SKUHERSKY ◽  
Tailin Wu ◽  
Eviatar Yemini ◽  
Edward Boyden ◽  
Max Tegmark
Keyword(s):  
Cell Fate ◽  
Point Clouds ◽  
Cell Identity ◽  
C Elegans ◽  
Neuronal Nuclei ◽  
Volumetric Images ◽  
Alignment Process ◽  
Learning Parameter ◽  
Automated Alignment ◽  
Limited Accuracy

Determining cell identity in volumetric images of tagged neuronal nuclei is an ongoing challenge in contemporary neuroscience. Frequently, cell identity is determined by aligning and matching tags to an "atlas" of labeled neuronal positions and other identifying characteristics. Previous analyses of such C. elegans datasets have been hampered by the limited accuracy of such atlases, especially for neurons present in the ventral nerve cord, and also by time-consuming manual elements of the alignment process. We present a novel automated alignment method for sparse and incomplete point clouds of the sort resulting from typical C. elegans fluorescence microscopy datasets. This method involves a tunable learning parameter and a kernel that enforces biologically realistic deformation. We also present a pipeline for creating alignment atlases from datasets of the recently developed NeuroPAL transgene. In combination, these advances allow us to label neurons in volumetric images with confidence much higher than previous methods. We release, to the best of our knowledge, the most complete C. elegans 3D positional neuron atlas, encapsulating positional variability derived from 7 animals, for the purposes of cell-type identity prediction for myriad applications (e.g., imaging neuronal activity, gene expression, and cell-fate).

scholarly journals The transcriptional corepressor CTBP-1 acts with the SOX family transcription factor EGL-13 to maintain AIA interneuron cell identity in C. elegans

2021 ◽  
Author(s):  
Josh Saul ◽  
Takashi Hirose ◽  
Robert Horvitz
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Cell Fate ◽  
Transcriptional Corepressor ◽  
Cell Identity ◽  
C Elegans ◽  
Dna Binding Specificity ◽  
A Cell ◽  
Transcriptional Corepressors ◽  
And Function

Cell identity is characterized by a distinct combination of gene expression, cell morphology and cellular function established as progenitor cells divide and differentiate. Following establishment, cell identities can be unstable and require active and continuous maintenance throughout the remaining life of a cell. Mechanisms underlying the maintenance of cell identities are incompletely understood. Here we show that the gene ctbp-1, which encodes the transcriptional corepressor C-terminal binding protein-1 (CTBP-1), is essential for the maintenance of the identities of the two AIA interneurons in the nematode Caenorhabditis elegans. ctbp-1 is not required for the establishment of the AIA cell fate but rather functions cell-autonomously and can act in older worms to maintain proper AIA gene expression, morphology and function. From a screen for suppressors of the ctbp-1 mutant phenotype, we identified the gene egl-13, which encodes a SOX family transcription factor. We found that egl-13 regulates AIA function and aspects of AIA gene expression, but not AIA morphology. We conclude that the CTBP-1 protein maintains AIA cell identity in part by utilizing EGL-13 to repress transcriptional activity in the AIAs. More generally, we propose that transcriptional corepressors like CTBP-1 might be critical factors in the maintenance of cell identities, harnessing the DNA-binding specificity of transcription factors like EGL-13 to selectively regulate gene expression in a cell-specific manner.

Centrosome Aurora A gradient ensures single polarity axis in C. elegans embryos

2020 ◽  
Vol 48 (3) ◽  
pp. 1243-1253 ◽  
Author(s):  
Sukriti Kapoor ◽  
Sachin Kotak
Keyword(s):  
Symmetry Breaking ◽  
Cell Fate ◽  
Cell Cortex ◽  
Axis Formation ◽  
Aurora A Kinase ◽  
Aurora A ◽  
C Elegans ◽  
Cell Embryo ◽  
Polarity Establishment

Cellular asymmetries are vital for generating cell fate diversity during development and in stem cells. In the newly fertilized Caenorhabditis elegans embryo, centrosomes are responsible for polarity establishment, i.e. anterior–posterior body axis formation. The signal for polarity originates from the centrosomes and is transmitted to the cell cortex, where it disassembles the actomyosin network. This event leads to symmetry breaking and the establishment of distinct domains of evolutionarily conserved PAR proteins. However, the identity of an essential component that localizes to the centrosomes and promotes symmetry breaking was unknown. Recent work has uncovered that the loss of Aurora A kinase (AIR-1 in C. elegans and hereafter referred to as Aurora A) in the one-cell embryo disrupts stereotypical actomyosin-based cortical flows that occur at the time of polarity establishment. This misregulation of actomyosin flow dynamics results in the occurrence of two polarity axes. Notably, the role of Aurora A in ensuring a single polarity axis is independent of its well-established function in centrosome maturation. The mechanism by which Aurora A directs symmetry breaking is likely through direct regulation of Rho-dependent contractility. In this mini-review, we will discuss the unconventional role of Aurora A kinase in polarity establishment in C. elegans embryos and propose a refined model of centrosome-dependent symmetry breaking.

scholarly journals Cadherins in early neural development

2021 ◽  
Author(s):  
Karolina Punovuori ◽  
Mattias Malaguti ◽  
Sally Lowell
Keyword(s):  
Adhesion Molecules ◽  
Cell Fate ◽  
Neural Development ◽  
Ex Vivo ◽  
Directed Differentiation ◽  
Culture Dish ◽  
Cell Identity ◽  
Cell Fate Decisions ◽  
Neural Tissues ◽  
And Function

AbstractDuring early neural development, changes in signalling inform the expression of transcription factors that in turn instruct changes in cell identity. At the same time, switches in adhesion molecule expression result in cellular rearrangements that define the morphology of the emerging neural tube. It is becoming increasingly clear that these two processes influence each other; adhesion molecules do not simply operate downstream of or in parallel with changes in cell identity but rather actively feed into cell fate decisions. Why are differentiation and adhesion so tightly linked? It is now over 60 years since Conrad Waddington noted the remarkable "Constancy of the Wild Type” (Waddington in Nature 183: 1654–1655, 1959) yet we still do not fully understand the mechanisms that make development so reproducible. Conversely, we do not understand why directed differentiation of cells in a dish is sometimes unpredictable and difficult to control. It has long been suggested that cells make decisions as 'local cooperatives' rather than as individuals (Gurdon in Nature 336: 772–774, 1988; Lander in Cell 144: 955–969, 2011). Given that the cadherin family of adhesion molecules can simultaneously influence morphogenesis and signalling, it is tempting to speculate that they may help coordinate cell fate decisions between neighbouring cells in the embryo to ensure fidelity of patterning, and that the uncoupling of these processes in a culture dish might underlie some of the problems with controlling cell fate decisions ex-vivo. Here we review the expression and function of cadherins during early neural development and discuss how and why they might modulate signalling and differentiation as neural tissues are formed.

scholarly journals Histone Acetyltransferases and Stem Cell Identity

Cancers ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2407
Author(s):  
Ruicen He ◽  
Arthur Dantas ◽  
Karl Riabowol
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Fate ◽  
Epigenetic Modification ◽  
Cell Types ◽  
Histone Acetyltransferases ◽  
Specific Cell ◽  
Cell Fates ◽  
Cell Identity ◽  
Hematopoietic Stem

Acetylation of histones is a key epigenetic modification involved in transcriptional regulation. The addition of acetyl groups to histone tails generally reduces histone-DNA interactions in the nucleosome leading to increased accessibility for transcription factors and core transcriptional machinery to bind their target sequences. There are approximately 30 histone acetyltransferases and their corresponding complexes, each of which affect the expression of a subset of genes. Because cell identity is determined by gene expression profile, it is unsurprising that the HATs responsible for inducing expression of these genes play a crucial role in determining cell fate. Here, we explore the role of HATs in the maintenance and differentiation of various stem cell types. Several HAT complexes have been characterized to play an important role in activating genes that allow stem cells to self-renew. Knockdown or loss of their activity leads to reduced expression and or differentiation while particular HATs drive differentiation towards specific cell fates. In this study we review functions of the HAT complexes active in pluripotent stem cells, hematopoietic stem cells, muscle satellite cells, mesenchymal stem cells, neural stem cells, and cancer stem cells.

scholarly journals CFP-1 interacts with HDAC1/2 complexes inC. elegansdevelopment

2018 ◽  
Author(s):  
Bharat Pokhrel ◽  
Yannic Chen ◽  
Jonathan Joseph Biro
Keyword(s):  
Cell Fate ◽  
Embryonic Stem ◽  
Stem Cell Differentiation ◽  
Embryonic Stem Cell Differentiation ◽  
Dependent Manner ◽  
Cell Fate Specification ◽  
C Elegans ◽  
Evolutionarily Conserved ◽  
Epigenetic Regulator ◽  
Inducible Genes

AbstractCFP-1 (CXXC finger binding protein 1) is an evolutionarily conserved protein that binds to non-methylated CpG-rich promoters in humans andC. elegans. This conserved epigenetic regulator is a part of the COMPASS complex that contains the H3K4me3 methyltransferase SET1 in mammals and SET-2 inC. elegans. Previous studies have indicated the importance ofcfp-1in embryonic stem cell differentiation and cell fate specification. However, neither the function nor the mechanism of action ofcfp-1is well understood at the organismal level. To further investigate the function of CFP-1, we have characterisedC. elegansCOMPASS mutantscfp-1(tm6369)andset-2(bn129). We found that bothcfp-1andset-2play an important role in the regulation of fertility and development of the organism. Furthermore, we found that bothcfp-1andset-2are required for H3K4 trimethylation and play a repressive role in the expression of heat shock and salt-inducible genes. Interestingly, we found thatcfp-1but notset-2genetically interacts with Histone Deacetylase (HDAC1/2) complexes to regulate fertility, suggesting a function of CFP-1 outside of the COMPASS complex. Additionally we found thatcfp-1andset-2acts on a separate pathways to regulate fertility and development ofC. elegans. Our results suggest that CFP-1 genetically interacts with HDAC1/2 complexes to regulate fertility, independent of its function within COMPASS complex. We propose that CFP-1 could cooperate with COMPASS complex and/or HDAC1/2 in a context dependent manner.

scholarly journals Genetic control of programmed cell death in the Caenorhabditis elegans hermaphrodite germline

Development ◽  
1999 ◽  
Vol 126 (5) ◽  
pp. 1011-1022 ◽  
Author(s):  
T.L. Gumienny ◽  
E. Lambie ◽  
E. Hartwieg ◽  
H.R. Horvitz ◽  
M.O. Hengartner
Keyword(s):  
Cell Death ◽  
Caenorhabditis Elegans ◽  
Germ Cell ◽  
Somatic Cell ◽  
Cell Fate ◽  
Germ Cells ◽  
Mapk Pathway ◽  
Apoptotic Cell ◽  
C Elegans ◽  
Pathway Activation

Development of the nematode Caenorhabditis elegans is highly reproducible and the fate of every somatic cell has been reported. We describe here a previously uncharacterized cell fate in C. elegans: we show that germ cells, which in hermaphrodites can differentiate into sperm and oocytes, also undergo apoptotic cell death. In adult hermaphrodites, over 300 germ cells die, using the same apoptotic execution machinery (ced-3, ced-4 and ced-9) as the previously described 131 somatic cell deaths. However, this machinery is activated by a distinct pathway, as loss of egl-1 function, which inhibits somatic cell death, does not affect germ cell apoptosis. Germ cell death requires ras/MAPK pathway activation and is used to maintain germline homeostasis. We suggest that apoptosis eliminates excess germ cells that acted as nurse cells to provide cytoplasmic components to maturing oocytes.

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