FLYWCH transcription factors act in a LIN-42/Period autoregulatory loop during gonad migration in C. elegans

Kinney, Brian, Menjivar-Hernandez, Jason, Koitz, Fred, Grinevich, Dmitry, Baselios, Madonna, Hammell, Christopher M, Gordon, Kacy Lynn (July 2025) FLYWCH transcription factors act in a LIN-42/Period autoregulatory loop during gonad migration in C. elegans. bioRxiv. ISSN 2692-8205 (Public Dataset) (Submitted)

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Abstract

Development must be coordinated across body systems but must also accommodate cell-type-specific processes. We discovered that the gene regulatory circuit controlling developmental timing in the Caenorhabditis elegans larval skin exhibits both points of convergence and divergence with the regulatory program governing the migration of the leader cell in gonad development, the distal tip cell (DTC). As a point of convergence, the conserved regulator of developmental timing, LIN-42/Period, peaks synchronously across cell types both during the L3 stage, when the DTC makes a turn in its normal migratory path, and the L4 stage in which the DTC normally continues straight ahead. We report that lin-42 , like its ortholog period , autorepresses its own transcription. lin-42 is required cell-autonomously for proper pathfinding of the DTC; DTC-specific lin-42 RNAi causes the DTC to turn in the mid-L4 instead of continuing straight ahead. We identified the FLYWCH transcription factor FLH-1 as able to directly bind the lin-42a promoter. Using live-cell imaging, we show that flh-1; flh-2 double mutant DTCs have an aberrant turn in the mid-L4. These mutants derepress the L4 peak of lin-42 expression in a stage- and DTC-specific manner, and this derepression is itself lin-42- dependent. During the aberrant mid-L4 turn in flh-1 ; flh-2 mutants, the focal adhesion factor TLN-1 is repolarized in the direction of turning. These results reveal that bodywide developmental rhythms can be fine-tuned to integrate with specific organogenic processes.

Item Type:	Paper
Subjects:	bioinformatics organism description > animal > C elegans bioinformatics > genomics and proteomics > genetics & nucleic acid processing bioinformatics > genomics and proteomics bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification organism description > animal bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > transcription factor
CSHL Authors:	Hammell, Christopher M.
Communities:	CSHL labs > Hammell C. lab
SWORD Depositor:	CSHL Elements
Depositing User:	CSHL Elements
Date:	11 July 2025
Date Deposited:	21 Jul 2025 12:10
Last Modified:	21 Jul 2025 12:10
PMCID:	PMC12265568
Related URLs:	Publisher
Dataset ID:	GEO: GSE52910
URI:	https://repository.cshl.edu/id/eprint/41911

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