BLMP-1/Blimp-1 regulates the spatiotemporal cell migration pattern in C. elegans

PLoS Genet. 2014 Jun 26;10(6):e1004428. doi: 10.1371/journal.pgen.1004428. eCollection 2014 Jun.

Abstract

Spatiotemporal regulation of cell migration is crucial for animal development and organogenesis. Compared to spatial signals, little is known about temporal signals and the mechanisms integrating the two. In the Caenorhabditis elegans hermaphrodite, the stereotyped migration pattern of two somatic distal tip cells (DTCs) is responsible for shaping the gonad. Guidance receptor UNC-5 is necessary for the dorsalward migration of DTCs. We found that BLMP-1, similar to the mammalian zinc finger transcription repressor Blimp-1/PRDI-BF1, prevents precocious dorsalward turning by inhibiting precocious unc-5 transcription and is only expressed in DTCs before they make the dorsalward turn. Constitutive expression of blmp-1 when BLMP-1 would normally disappear delays unc-5 transcription and causes turn retardation, demonstrating the functional significance of blmp-1 down-regulation. Correct timing of BLMP-1 down-regulation is redundantly regulated by heterochronic genes daf-12, lin-29, and dre-1, which regulate the temporal fates of various tissues. DAF-12, a steroid hormone receptor, and LIN-29, a zinc finger transcription factor, repress blmp-1 transcription, while DRE-1, the F-Box protein of an SCF ubiquitin ligase complex, binds to BLMP-1 and promotes its degradation. We have therefore identified a gene circuit that integrates the temporal and spatial signals and coordinates with overall development of the organism to direct cell migration during organogenesis. The tumor suppressor gene product FBXO11 (human DRE-1 ortholog) also binds to PRDI-BF1 in human cell cultures. Our data suggest evolutionary conservation of these interactions and underscore the importance of DRE-1/FBXO11-mediated BLMP-1/PRDI-BF1 degradation in cellular state transitions during metazoan development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caenorhabditis elegans / genetics*
  • Caenorhabditis elegans / growth & development
  • Caenorhabditis elegans Proteins / genetics*
  • Cell Movement / genetics
  • Evolution, Molecular
  • F-Box Proteins / genetics*
  • F-Box Proteins / metabolism
  • Gene Expression Regulation, Developmental
  • Gonads / growth & development
  • Gonads / metabolism
  • Humans
  • Organogenesis / genetics*
  • Positive Regulatory Domain I-Binding Factor 1
  • Proteolysis
  • Receptors, Cell Surface / genetics
  • Repressor Proteins / genetics*

Substances

  • Caenorhabditis elegans Proteins
  • DRE-1 protein, C elegans
  • F-Box Proteins
  • Receptors, Cell Surface
  • Repressor Proteins
  • blmp-1 protein, C elegans
  • PRDM1 protein, human
  • UNC-5 protein, C elegans
  • Positive Regulatory Domain I-Binding Factor 1

Grants and funding

This work was supported, in part, by Ministry of Science and Technology (Taiwan) grant 102-2627-M-002-005 and NTU grant 103R7602A3. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.