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Norway

PMID:38776905  

The Rac pathway prevents cell fragmentation in a nonprotrusively migrating leader cell during C. elegans gonad organogenesis.

Noor Singh | Pu Zhang | Karen Jian Li | Kacy Lynn Gordon
Current biology : CB | 2024

The C. elegans hermaphrodite distal tip cell (DTC) leads gonadogenesis. Loss-of-function mutations in a C. elegans ortholog of the Rac1 GTPase (ced-10) and its GEF complex (ced-5/DOCK180, ced-2/CrkII, ced-12/ELMO) cause gonad migration defects related to directional sensing; we discovered an additional defect class of gonad bifurcation in these mutants. Using genetic approaches, tissue-specific and whole-body RNAi, and in vivo imaging of endogenously tagged proteins and marked cells, we find that loss of Rac1 or its regulators causes the DTC to fragment as it migrates. Both products of fragmentation-the now-smaller DTC and the membranous patch of cellular material-localize important stem cell niche signaling (LAG-2 ligand) and migration (INA-1/integrin subunit alpha) factors to their membranes, but only one retains the DTC nucleus and therefore the ability to maintain gene expression over time. The enucleate patch can lead a bifurcating branch off the gonad arm that grows through germ cell proliferation. Germ cells in this branch differentiate as the patch loses LAG-2 expression. While the nucleus is surprisingly dispensable for aspects of leader cell function, it is required for stem cell niche activity long term. Prior work found that Rac1-/-;Rac2-/- mouse erythrocytes fragment; in this context, our new findings support the conclusion that maintaining a cohesive but deformable cell is a conserved function of this important cytoskeletal regulator.

Pubmed ID: 38776905

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HT115 (organism)

RRID:WB-STRAIN:WBStrain00041079

Escherichia coli with name E. coli [F-, mcrA, mcrB, IN(rrnD-rrnE)1, rnc14::Tn10(DE3 lysogen: lacUV5 promoter -T7 polymerase]. from WB.

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Caenorhabditis Genetics Center (biomaterial supply resource)

RRID:SCR_007341

Center that acquires, maintains, and distributes genetic stocks and information about stocks of the small free-living nematode Caenorhabditis elegans for use by investigators initiating or continuing research on this genetic model organism. A searchable strain database, general information about C. elegans, and links to key Web sites of use to scientists, including WormBase, WormAtlas, and WormBook are available.

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VC1848 (organism)

RRID:WB-STRAIN:WBStrain00036921

Caenorhabditis elegans with name mom-5(gk812) I/hT2 [bli-4(e937) let-?(q782) qIs48] (I;III). from WB.

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MT5013 (organism)

RRID:WB-STRAIN:WBStrain00027188

Caenorhabditis elegans with name ced-10(n1993) IV. from WB.

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Caenorhabditis Genetics Center (biomaterial supply resource)

RRID:SCR_007341

Center that acquires, maintains, and distributes genetic stocks and information about stocks of the small free-living nematode Caenorhabditis elegans for use by investigators initiating or continuing research on this genetic model organism. A searchable strain database, general information about C. elegans, and links to key Web sites of use to scientists, including WormBase, WormAtlas, and WormBook are available.

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MT11068 (organism)

RRID:WB-STRAIN:WBStrain00027386

Caenorhabditis elegans with name ced-12(n3261) I. from WB.

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Caenorhabditis Genetics Center (biomaterial supply resource)

RRID:SCR_007341

Center that acquires, maintains, and distributes genetic stocks and information about stocks of the small free-living nematode Caenorhabditis elegans for use by investigators initiating or continuing research on this genetic model organism. A searchable strain database, general information about C. elegans, and links to key Web sites of use to scientists, including WormBase, WormAtlas, and WormBook are available.

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Caenorhabditis Genetics Center (biomaterial supply resource)

RRID:SCR_007341

Center that acquires, maintains, and distributes genetic stocks and information about stocks of the small free-living nematode Caenorhabditis elegans for use by investigators initiating or continuing research on this genetic model organism. A searchable strain database, general information about C. elegans, and links to key Web sites of use to scientists, including WormBase, WormAtlas, and WormBook are available.

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MT4434 (organism)

RRID:WB-STRAIN:WBStrain00027134

Caenorhabditis elegans with name ced-5(n1812) IV. from WB.

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MT4952 (organism)

RRID:WB-STRAIN:WBStrain00027171

Caenorhabditis elegans with name ced-2(n1994) IV. from WB.

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C. elegans RNAi Collection (Ahringer) (data or information resource)

RRID:SCR_017064

C. elegans RNAi feeding library distributed by Source BioScience Ltd. Designed for genome wide study of gene function in C. elegans through loss of function studies.

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OP50 (organism)

RRID:WB-STRAIN:WBStrain00041969

Escherichia coli with name E. coli. from WB.

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