Menu

Close

Neural crest cells regulate optic cup morphogenesis by promoting extracellular matrix assembly

Chase Dallas Bryan, Rebecca Lynne Pfeiffer, Bryan William Jones, Kristen Marie Kwan

Preprint posted on July 22, 2018 https://www.biorxiv.org/content/early/2018/07/22/374470

Ocular Origami: Bryan and colleagues discover that in the developing zebrafish eye, cell and tissue movements in the optic cup are dependent on the extracellular matrix protein nidogen provided by surrounding neural crest cells.

Selected by Ashrifia Adomako-Ankomah

Background
During embryogenesis, eye development is marked by several critical cell and tissue movement events. As reviewed by Cavodeassi (2018), zebrafish eye development begins with the specification of the eye field cells. These cells then evaginate to form the optic vesicles. The distal edges of the optic vesicles subsequently invaginate, and the optic cup is formed. The optic cup has two layers- the outer layer forms the retinal pigment epithelium (RPE), and the inner layer forms the neural retina. The developing optic cup is surrounded by a periocular mesenchyme (POM) made up of neural crest and mesoderm-derived mesenchyme cells. The POM is known to influence cell migration during eye development, though the exact mechanisms by which this happens are not fully resolved. In this preprint, Bryan and colleagues take advantage of advances in microscopy and live imaging technology to examine in detail the role of the POM neural crest cells in regulating tissue movements during optic cup morphogenesis.

Interesting findings
The authors first set out to determine the location of neural crest cells in the region of the developing eye. For this, they employ the vast transgenic toolkit available to zebrafish researchers by crossing two fish lines: one in which GFP labels all cell membranes, and the other in which RFP labels only neural crest membranes. Results from 4-dimensional time lapse imaging in these double-labeled fish show the gradual migration of neural crest cells around and in close contact with the developing optic cup until they surround the RPE.

 

Preprint Supplemental Movie 1

To identify the function of the neural crest cells, eye development was observed in two mutant fish lines (the tfap2a;foxd3 double mutant and the paf1 mutant) in which these cells were depleted. When compared to wild type siblings, neural crest mutants had defects in early optic cup invagination, leading to malformations of the eye.

                 Preprint Figure 2

The authors then used confocal imaging to track the migration paths of individual cells to figure out exactly which cell movements were regulated by neural crest cells. Results showed that migrating cells in mutant embryos did not follow the stereotypical trajectory seen in wild type embryos. In neural crest mutants, these cells traveled farther, faster, and were found in a wider area than cells in control embryos.

How do neural crest cells control cell migration? As the basement membrane of the RPE was disorganized in neural crest mutants, it was plausible that some component of the ECM was missing in the absence of neural crest cells. In situ hybridization data revealed that nidogen, an ECM crosslinking protein known to regulate basement membrane assembly, was expressed in neural crest cells surrounding the RPE and lost in neural crest mutants. Blocking the function of nidogen perturbed lens morphogenesis, and the general overexpression of nidogen partially rescued eye defects in neural crest mutants. Additionally, the overexpression of nidogen in a wild type background also led to optic cup invagination defects.

The authors conclude that nidogen produced by the neural crest cells is required for the proper formation of the basement membrane of the RPE. This creates a restrictive environment, helping cells in the optic vesicle migrate to the right location as the optic cup invaginates.

      Preprint Figure 10

What I like about this preprint
This preprint makes good use of the ability to make stable mutant and transgenic lines in zebrafish. The gorgeous confocal images shown provide great detail on a single-cell level, and the movies are fascinating to watch. Also, imaging data were captured prior to genotyping the embryos used, ensuring objectivity in data collection.

Follow-up question
What do the authors speculate is the role, if any, of the mesoderm-derived mesenchyme cells of the POM in regulating optic cup morphogenesis?

Reference
1. Cavodeassi, F. (2018) Dynamic Tissue Rearrangements during Vertebrate Eye Morphogenesis: Insights from Fish Models. Journal of Developmental Biology 6(1), 4

Tags: cell migration, extracellular matrix, eye cup morphogenesis, eye development, neural crest cells, nidogen, zebrafish

Posted on: 30th August 2018

Read preprint (No Ratings Yet)




  • Author's response

    Dr. Kristen M. Kwan shared

    We agree that the follow-up question you’ve raised is indeed a very interesting one (and one we are interested in pursuing in the future).

    Have your say

    Your email address will not be published. Required fields are marked *

    This site uses Akismet to reduce spam. Learn how your comment data is processed.

    Sign up to customise the site to your preferences and to receive alerts

    Register here

    Also in the cell biology category:

    The autophagic membrane tether ATG2A transfers lipids between membranes

    Shintaro Maeda, Chinatsu Otomo, Takanori Otomo



    Selected by Sandra Malmgren Hill

    LTK is an ER-resident receptor tyrosine kinase that regulates secretion

    Federica G. Centonze, Veronika Reiterer, Karsten Nalbach, et al.



    Selected by Nicola Stevenson

    1

    Distinct RhoGEFs activate apical and junctional actomyosin contractility under control of G proteins during epithelial morphogenesis

    Alain Garcia De Las Bayonas, Jean-Marc Philippe, Annemarie C. Lellouch, et al.



    Selected by Ivana Viktorinová

    1

    In vivo glucose imaging in multiple model organisms with an engineered single-wavelength sensor

    Jacob P. Keller, Jonathan S. Marvin, Haluk Lacin, et al.



    Selected by Stephan Daetwyler

    1

    The spindle assembly checkpoint functions during early development in non-chordate embryos

    Janet Chenevert, Marianne Roca, Lydia Besnardeau, et al.



    Selected by Maiko Kitaoka

    Blue light induces neuronal-activity-regulated gene expression in the absence of optogenetic proteins

    Kelsey M. Tyssowski, Jesse M. Gray



    Selected by Zheng-Shan Chong

    Mutations in the Insulator Protein Suppressor of Hairy Wing Induce Genome Instability

    Shih-Jui Hsu, Emily C. Stow, James R. Simmons, et al.



    Selected by Maiko Kitaoka

    1

    Multi-immersion open-top light-sheet microscope for high-throughput imaging of cleared tissues

    Adam K. Glaser, Nicholas P. Reder, Ye Chen, et al.



    Selected by Tim Fessenden

    1

    ATAT1-enriched vesicles promote microtubule acetylation via axonal transport

    Aviel Even, Giovanni Morelli, Chiara Scaramuzzino, et al.



    Selected by Stephen Royle

    1

    HIV-1 Gag specifically restricts PI(4,5)P2 and cholesterol mobility in living cells creating a nanodomain platform for virus assembly

    C. Favard, J. Chojnacki, P. Merida, et al.



    Selected by Amberley Stephens

    Hepatocyte-specific deletion of Pparα promotes NASH in the context of obesity

    Marion Regnier, Arnaud Polizzi, Sarra Smati, et al.



    Selected by Pablo Ranea Robles

    Mitochondrial biogenesis is transcriptionally repressed in lysosomal lipid storage diseases

    King Faisal Yambire, Lorena Fernandez-Mosquera, Robert Steinfeld, et al.



    Selected by Sandra Franco Iborra

    1

    Thyroid hormone regulates distinct paths to maturation in pigment cell lineages

    Lauren Saunders, Abhishek Mishra, Andrew J Aman, et al.



    Selected by Hannah Brunsdon

    1

    Kinesin-6 Klp9 plays motor-dependent and -independent roles in collaboration with Kinesin-5 Cut7 and the microtubule crosslinker Ase1 in fission yeast

    Masashi Yukawa, Masaki Okazaki, Yasuhiro Teratani, et al.



    Selected by I. Bouhlel

    A pair of E3 ubiquitin ligases compete to regulate filopodial dynamics and axon guidance

    Nicholas P Boyer, Laura E McCormick, Fabio L Urbina, et al.



    Selected by Angika Basant

    1

    SorCS1-mediated Sorting of Neurexin in Dendrites Maintains Presynaptic Function

    Luis Filipe Ribeiro, Ben Verpoort, Julie Nys, et al.



    Selected by Carmen Adriaens

    1

    Also in the developmental biology category:

    The visual system of the genetically tractable crustacean Parhyale hawaiensis: diversification of eyes and visual circuits associated with low-resolution vision

    Ana Patricia Ramos, Ola Gustafsson, Nicolas Labert, et al.



    Selected by Alexa Sadier

    Distinct RhoGEFs activate apical and junctional actomyosin contractility under control of G proteins during epithelial morphogenesis

    Alain Garcia De Las Bayonas, Jean-Marc Philippe, Annemarie C. Lellouch, et al.



    Selected by Ivana Viktorinová

    1

    The Hunchback temporal transcription factor determines motor neuron axon and dendrite targeting in Drosophila

    Austin Q Seroka, Chris Q Doe



    Selected by Abagael Lasseigne

    1

    Preformed Chromatin Topology Assists Transcriptional Robustness of Shh during Limb Development

    Christina Paliou, Philine Guckelberger, Robert Schöpflin, et al.



    Selected by Rafael Galupa

    1

    Molecular Logic of Spinocerebellar Tract Neuron Diversity and Connectivity

    Myungin Baek, Vilas Menon, Thomas Jessell, et al.



    Selected by Yen-Chung Chen

    In vivo glucose imaging in multiple model organisms with an engineered single-wavelength sensor

    Jacob P. Keller, Jonathan S. Marvin, Haluk Lacin, et al.



    Selected by Stephan Daetwyler

    1

    Active behaviour during early development shapes glucocorticoid reactivity

    Luis A. Castillo-Ramírez, Soojin Ryu, Rodrigo J. De Marco



    Selected by Kathleen Gilmour

    A unicellular relative of animals generates an epithelium-like cell layer by actomyosin-dependent cellularization

    Omaya Dudin, Andrej Ondracka, Xavier Grau-Bové, et al.



    Selected by Paul Gerald L. Sanchez and Stefano Vianello

    1

    Members of the Arabidopsis auxin receptor gene family are essential early in embryogenesis and have broadly overlapping functions

    Michael J Prigge, Nikita Kadakia, Kathleen Greenham, et al.



    Selected by Chandra Shekhar Misra

    1

    The spindle assembly checkpoint functions during early development in non-chordate embryos

    Janet Chenevert, Marianne Roca, Lydia Besnardeau, et al.



    Selected by Maiko Kitaoka

    Over-activation of BMP signaling in neural crest cells precipitates heart outflow tract septation

    Jean Francois Darrigrand, Mariana Valente, Pauline Martinez, et al.



    Selected by Giulia Boezio

    Mutations in the Insulator Protein Suppressor of Hairy Wing Induce Genome Instability

    Shih-Jui Hsu, Emily C. Stow, James R. Simmons, et al.



    Selected by Maiko Kitaoka

    1

    Multi-immersion open-top light-sheet microscope for high-throughput imaging of cleared tissues

    Adam K. Glaser, Nicholas P. Reder, Ye Chen, et al.



    Selected by Tim Fessenden

    1

    Dynamic Erasure of Random X-Chromosome Inactivation during iPSC Reprogramming

    Adrian Janiszewski, Irene Talon, Juan Song, et al.



    Selected by Sergio Menchero

    MicroRNA-mediated control of developmental lymphangiogenesis

    Hyun Min Jung, Ciara Hu, Alexandra M Fister, et al.



    Selected by Rudra Nayan Das

    Endogenous CRISPR arrays for scalable whole organism lineage tracing

    James Cotterell, James Sharpe



    Selected by Irepan Salvador-Martinez

    Also in the genetics category:

    The Hunchback temporal transcription factor determines motor neuron axon and dendrite targeting in Drosophila

    Austin Q Seroka, Chris Q Doe



    Selected by Abagael Lasseigne

    1

    Preformed Chromatin Topology Assists Transcriptional Robustness of Shh during Limb Development

    Christina Paliou, Philine Guckelberger, Robert Schöpflin, et al.



    Selected by Rafael Galupa

    1

    Molecular Logic of Spinocerebellar Tract Neuron Diversity and Connectivity

    Myungin Baek, Vilas Menon, Thomas Jessell, et al.



    Selected by Yen-Chung Chen

    Over-activation of BMP signaling in neural crest cells precipitates heart outflow tract septation

    Jean Francois Darrigrand, Mariana Valente, Pauline Martinez, et al.



    Selected by Giulia Boezio

    Functional dissection of TADs reveals non-essential and instructive roles in regulating gene expression

    Alexandra Despang, Robert Schöpflin, Martin Franke, et al.



    Selected by Clarice Hong

    Crowdfunded whole-genome sequencing of the celebrity cat Lil BUB identifies causal mutations for her osteopetrosis and polydactyly

    Mike Bridavsky, Heiner Kuhl, Arthur Woodruf, et al.



    Selected by Jesus Victorino, Gabriel Aughey

    1

    Dynamic Erasure of Random X-Chromosome Inactivation during iPSC Reprogramming

    Adrian Janiszewski, Irene Talon, Juan Song, et al.



    Selected by Sergio Menchero

    Kinesin-6 Klp9 plays motor-dependent and -independent roles in collaboration with Kinesin-5 Cut7 and the microtubule crosslinker Ase1 in fission yeast

    Masashi Yukawa, Masaki Okazaki, Yasuhiro Teratani, et al.



    Selected by I. Bouhlel

    Human Handedness: Genetics, Microtubules, Neuropsychiatric Diseases and Brain Language Areas

    Akira Wiberg, Gwenaelle Douaud, Michael Ng, et al.



    Selected by Jose Guerrero

    The Spatio-Temporal Control of Zygotic Genome Activation

    George Gentsch, Nick D. L. Owens, James C. Smith



    Selected by Meng Zhu

    Multilevel regulation of the glass locus during Drosophila eye development

    Cornelia Fritsch, F. Javier Bernardo-Garcia, Tim Humberg, et al.



    Selected by Gabriel Aughey

    1

    Distinct ROPGEFs successively drive polarization and outgrowth of root hairs

    Philipp Denninger, Anna Reichelt, Vanessa Aphaia Fiona Schmidt, et al.



    Selected by Marc Somssich

    A direct and widespread role for the nuclear receptor EcR in mediating the response to ecdysone in Drosophila

    Christopher M Uyehara, Daniel J McKay



    Selected by Natalie Dye

    MRE11-RAD50-NBS1 activates Fanconi Anemia R-loop suppression at transcription-replication conflicts

    Emily Yun-Chia Chang, James P Wells, Shu-Huei Tsai, et al.



    Selected by Katie Weiner

    1

    Super-resolution Molecular Map of Basal Foot Reveals Novel Cilium in Airway Multiciliated Cells

    Quynh Nguyen, Zhen Liu, Rashmi Nanjundappa, et al.



    Selected by Robert Mahen

    Single cell RNA-Seq reveals distinct stem cell populations that drive sensory hair cell regeneration in response to loss of Fgf and Notch signaling

    Mark E. Lush, Daniel C. Diaz, Nina Koenecke, et al.

    AND

    Distinct progenitor populations mediate regeneration in the zebrafish lateral line.

    Eric D Thomas, David Raible



    Selected by Rudra Nayan Das

    2

    Close