TIAM-1/GEF can shape somatosensory dendrites independently of its GEF activity by regulating F-actin localization

Abstract

Dendritic arbors are a crucial for nervous system assembly, but the intracellular mechanisms that govern their assembly remain incompletely understood. Here we show that the dendrites of PVD neurons in Caenorhabditis elegans are patterned by distinct pathways downstream of the DMA-1 leucine rich transmembrane (LRR-TM) receptor. DMA-1/LRR-TM interacts through a PDZ ligand motif with the guanine nucleotide exchange factor TIAM-1/GEF in a complex with act-4/Actin to pattern higher order 4º dendrite branches by localizing F-actin to the distal ends of developing dendrites. Surprisingly, TIAM-1/GEF appears to function independently of Rac1 guanine nucleotide exchange factor activity. A partially redundant pathway, dependent on HPO-30/Claudin, regulates formation of 2º and 3º branches, possibly by regulating membrane localization and trafficking of DMA-1/LRR-TM. Collectively, our experiments suggest that HPO-30/Claudin localizes the DMA-1/LRR-TM receptor on PVD dendrites, which in turn can control dendrite patterning by directly modulating F-actin dynamics through TIAM-1/GEF.

Data availability

All data generated or analyzed during this study are included in the manuscript and supporting files.

Article and author information

Author details

  1. Leo TH Tang

    Department of Genetics, Albert Einstein College of Medicine, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Carlos A Diaz-Balzac

    Department of Genetics, Albert Einstein College of Medicine, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4723-1282
  3. Maisha Rahman

    Dominick P Purpura Department of Neuroscience, Albert Einstein College of Medicine, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Nelson J Ramirez-Suarez

    Department of Genetics, Albert Einstein College of Medicine, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7394-860X
  5. Yehuda Salzberg

    Department of Genetics, Albert Einstein College of Medicine, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Maria I Lázaro-Peña

    Department of Genetics, Albert Einstein College of Medicine, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Hannes E Bülow

    Department of Genetics, Albert Einstein College of Medicine, New York, United States
    For correspondence
    hannes.buelow@einstein.yu.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6271-0572

Funding

National Institute of Neurological Disorders and Stroke (R21NS081505)

  • Hannes E Bülow

National Institute of General Medical Sciences (T32GM007288)

  • Carlos A Diaz-Balzac

Eunice Kennedy Shriver National Institute of Child Health and Human Development (F31HD066967)

  • Carlos A Diaz-Balzac

Fulbright-Colciencias

  • Nelson J Ramirez-Suarez

Irma T Hirschl/Monique Weill-Caulier

  • Hannes E Bülow

National Institute of Neurological Disorders and Stroke (F31NS100370)

  • Maisha Rahman

National Institute of General Medical Sciences (T32GM07491)

  • Maria I Lázaro-Peña

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Copyright

© 2019, Tang et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 2,087
    views
  • 245
    downloads
  • 35
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Leo TH Tang
  2. Carlos A Diaz-Balzac
  3. Maisha Rahman
  4. Nelson J Ramirez-Suarez
  5. Yehuda Salzberg
  6. Maria I Lázaro-Peña
  7. Hannes E Bülow
(2019)
TIAM-1/GEF can shape somatosensory dendrites independently of its GEF activity by regulating F-actin localization
eLife 8:e38949.
https://doi.org/10.7554/eLife.38949

Share this article

https://doi.org/10.7554/eLife.38949

Further reading

    1. Developmental Biology
    Shuhei So, Masayo Asakawa, Hitoshi Sawa
    Research Article

    Organogenesis requires the proper production of diverse cell types and their positioning/migration. However, the coordination of these processes during development remains poorly understood. The gonad in C. elegans exhibits a mirror-symmetric structure guided by the migration of distal tip cells (DTCs), which result from asymmetric divisions of somatic gonadal precursors (SGPs; Z1 and Z4). We found that the polarity of Z1 and Z4, which possess mirror-symmetric orientation, is controlled by the redundant functions of the LIN-17/Frizzled receptor and three Wnt proteins (CWN-1, CWN-2, and EGL-20) with distinct functions. In lin-17 mutants, CWN-2 promotes normal polarity in both Z1 and Z4, while CWN-1 promotes reverse and normal polarity in Z1 and Z4, respectively. In contrast, EGL-20 inhibits the polarization of both Z1 and Z4. In lin-17 egl-20 cwn-2 triple mutants with a polarity reversal of Z1, DTCs from Z1 frequently miss-migrate to the posterior side. Our further analysis demonstrates that the mis-positioning of DTCs in the gonad due to the polarity reversal of Z1 leads to mis-migration. Similar mis-migration was also observed in cki-1(RNAi) animals producing ectopic DTCs. These results highlight the role of Wnt signaling in coordinating the production and migration of DTCs to establish a mirror-symmetric organ.

    1. Developmental Biology
    Michele Bertacchi, Gwendoline Maharaux ... Michèle Studer
    Research Article

    The morphogen FGF8 establishes graded positional cues imparting regional cellular responses via modulation of early target genes. The roles of FGF signaling and its effector genes remain poorly characterized in human experimental models mimicking early fetal telencephalic development. We used hiPSC-derived cerebral organoids as an in vitro platform to investigate the effect of FGF8 signaling on neural identity and differentiation. We found that FGF8 treatment increases cellular heterogeneity, leading to distinct telencephalic and mesencephalic-like domains that co-develop in multi-regional organoids. Within telencephalic domains, FGF8 affects the anteroposterior and dorsoventral identity of neural progenitors and the balance between GABAergic and glutamatergic neurons, thus impacting spontaneous neuronal network activity. Moreover, FGF8 efficiently modulates key regulators responsible for several human neurodevelopmental disorders. Overall, our results show that FGF8 signaling is directly involved in both regional patterning and cellular diversity in human cerebral organoids and in modulating genes associated with normal and pathological neural development.