Mechanisms of lineage specification in <i>Caenorhabditis elegans</i>

Liu, Jun; Murray, John Isaac

doi:10.1093/genetics/iyad174

Cited by 8 publications

(4 citation statements)

References 455 publications

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“…Its third generation can be classified by three shape descriptors (i.e., the Hayakawa roundness, general sphericity, and the spreading index) that exhibit substantially smaller or larger values in cells from different sublineages but in the symmetric (same) lineal position, rather than their sisters or cousins ( Figure 7 a,b), but they were found to be significantly correlated to one another ( Figure S5 ). In particular, Dxa (Daa and Dap) were the outliers in all D cells, although all of the terminal progeny within the D lineage differentiated into the body wall muscle without exception [ 15 , 56 , 57 ]. Fascinatingly, previous experimental reports demonstrated two transcription factors that show binary expression in line with the differentiated shapes of D cells.…”

Section: Resultsmentioning

confidence: 99%

Characterizing Cellular Physiological States with Three-Dimensional Shape Descriptors for Cell Membranes

Guan,

Chen,

Wang

et al. 2024

Membranes

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The shape of a cell as defined by its membrane can be closely associated with its physiological state. For example, the irregular shapes of cancerous cells and elongated shapes of neuron cells often reflect specific functions, such as cell motility and cell communication. However, it remains unclear whether and which cell shape descriptors can characterize different cellular physiological states. In this study, 12 geometric shape descriptors for a three-dimensional (3D) object were collected from the previous literature and tested with a public dataset of ~400,000 independent 3D cell regions segmented based on fluorescent labeling of the cell membranes in Caenorhabditis elegans embryos. It is revealed that those shape descriptors can faithfully characterize cellular physiological states, including (1) cell division (cytokinesis), along with an abrupt increase in the elongation ratio; (2) a negative correlation of cell migration speed with cell sphericity; (3) cell lineage specification with symmetrically patterned cell shape changes; and (4) cell fate specification with differential gene expression and differential cell shapes. The descriptors established may be used to identify and predict the diverse physiological states in numerous cells, which could be used for not only studying developmental morphogenesis but also diagnosing human disease (e.g., the rapid detection of abnormal cells).

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Section: Resultsmentioning

confidence: 99%

Characterizing Cellular Physiological States with Three-Dimensional Shape Descriptors for Cell Membranes

Guan,

Chen,

Wang

et al. 2024

Membranes

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“…By taking advantage of a partial loss-of-function allele of sem-2 , we have identified additional functions of the single C. elegans SoxC protein, SEM-2, and uncovered previously unappreciated regulatory relationships between SEM-2 and LET-381/FoxF/C, as well as between SEM-2 and HLH-8/Twist. Our work added new subcircuits to the gene regulatory network underlying C. elegans postembryonic development [2].…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies have identified multiple transcription factors and signaling components essential for the proper development of the M lineage [2]. In particular, LIN-12/Notch signaling is known to function upstream of the single C. elegans SoxC protein, SEM-2, to specify the SM fate in the ventral M lineage, while the zinc finger transcription factor SMA-9 antagonizes BMP signaling to specify the M lineage-derived CC (M-CC for short) fate in the dorsal side [3–6].…”

Section: Introductionmentioning

confidence: 99%

SEM-2/SoxC regulates multiple aspects ofC. eleganspostembryonic mesoderm development

Baccas,

Ganesan,

Leung

et al. 2024

Preprint

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Development of multicellular organisms requires well-orchestrated interplay between cell-intrinsic transcription factors and cell-cell signaling. One set of highly conserved transcription factors that plays diverse roles in development is the SoxC group.C. eleganscontains a sole SoxC protein, SEM-2. SEM-2 is essential for embryonic development, and for specifying the sex myoblast (SM) fate in the postembryonic mesoderm, the M lineage. We have identified a novel partial loss-of-functionsem-2allele that has a proline to serine change in the C-terminal tail of the highly conserved DNA-binding domain. Detailed analyses of mutant animals harboring this point mutation uncovered new functions of SEM-2 in the M lineage. First, SEM-2 functions antagonistically with LET-381, the soleC. elegansFoxF/C forkhead transcription factor, to regulate dorsoventral patterning of the M lineage. Second, in addition to specifying the SM fate, SEM-2 is essential for the proliferation and diversification of the SM lineage. Finally, SEM-2 appears to directly regulate the expression ofhlh-8, which encodes a basic helix-loop-helix Twist transcription factor and plays critical roles in proper patterning of the M lineage. Our data, along with previous studies, suggest an evolutionarily conserved relationship between SoxC and Twist proteins. Furthermore, our work identified new interactions in the gene regulatory network (GRN) underlyingC. eleganspostembryonic development and adds to the general understanding of the structure-function relationship of SoxC proteins.AUTHOR SUMMARYSoxC transcription factors play important roles in metazoan development. Abnormal expression or function of SoxC factors has been linked to a variety of developmental disorders and cancers. It is therefore critical to understand the functions of SoxC proteins in vivo.C. eleganshas a single SoxC transcription factor, SEM-2, that is known to regulate a fate decision between a proliferative progenitor cell vs. a terminally differentiated cell during postembryonic mesoderm development. In this study, we report new functions of SEM-2 in postembryonic mesoderm development via our studies of a partial loss-of-function allele ofsem-2. Our work uncovers new regulatory relationships between SEM-2/SoxC and the FoxF/C transcription factor LET-381, and between SEM-2/SoxC and theC. elegansTwist ortholog HLH-8. Our findings suggest that the SoxC-Twist axis, including the downstream targets of Twist, represents an evolutionarily conserved regulatory cassette important in metazoan development.

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“…The development of the nematode C. elegans is essentially invariant and provides a unique opportunity to study cell fate and how a cell acquires a specific fate during its lineage history, i.e. the successive rounds of cell division starting from the first division of the one-cell embryo to the terminal division that generates that cell 7 . Most terminal divisions during C. elegans development are asymmetric and result in two daughter cells that adopt different fates 8,9 .…”

Section: Introductionmentioning

confidence: 99%

The replicative helicase CMG is required for the divergence of cell fates during asymmetric cell divisionin vivo

Memar,

Sherrard,

Sethi

et al. 2024

Preprint

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The mechanisms that enable differential gene expression in daughter cells produced by asymmetric cell divisions are not well understood. We discovered that the eukaryotic replicative helicase CMG (Cdc45-MCM-GINS) is required for this process inC. elegans. DuringC. elegansdevelopment, some dividing cells give rise to a daughter that survives and a daughter that dies. We found that PSF-2 GINS2, a component ofC. elegansCMG, is necessary for the transcriptional burst of the pro-apoptotic geneegl-1BH3-only, which occurs in the daughter that dies immediately following mother cell division. We present evidence that this requirement is independent of the function of CMG in DNA unwinding. We propose that the recently described histone chaperone activity of CMG causes epigenetic changes at theegl-1locus during replication in mother cells, and that these changes are required for the increase inegl-1transcription in the daughter that dies. We also find that PSF-2 is required for the divergence of other cell fates duringC. elegansdevelopment, suggesting that this function is not restricted to the regulation ofegl-1expression. Our work uncovers a new and unexpected role of CMG in cell fate and a novel intrinsic mechanism for gene expression plasticity in the context of asymmetric cell division.

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Mechanisms of lineage specification in Caenorhabditis elegans

Cited by 8 publications

References 455 publications

Characterizing Cellular Physiological States with Three-Dimensional Shape Descriptors for Cell Membranes

Characterizing Cellular Physiological States with Three-Dimensional Shape Descriptors for Cell Membranes

SEM-2/SoxC regulates multiple aspects ofC. eleganspostembryonic mesoderm development

The replicative helicase CMG is required for the divergence of cell fates during asymmetric cell divisionin vivo

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