Toddler signaling regulates mesodermal cell migration downstream of Nodal signaling

Toddler/Apela/Elabela is a conserved secreted peptide that regulates mesendoderm development during zebrafish gastrulation. Two non-exclusive models have been proposed to explain Toddler function. The ‘specification model’ postulates that Toddler signaling enhances Nodal signaling to properly specify endoderm, whereas the ‘migration model’ posits that Toddler signaling regulates mesendodermal cell migration downstream of Nodal signaling. Here, we test key predictions of both models. We find that in toddler mutants Nodal signaling is initially normal and increasing endoderm specification does not rescue mesendodermal cell migration. Mesodermal cell migration defects in toddler mutants result from a decrease in animal pole-directed migration and are independent of endoderm. Conversely, endodermal cell migration defects are dependent on a Cxcr4a-regulated tether of the endoderm to mesoderm. These results suggest that Toddler signaling regulates mesodermal cell migration downstream of Nodal signaling and indirectly affects endodermal cell migration via Cxcr4a-signaling.

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Author response: Toddler signaling regulates mesodermal cell migration downstream of Nodal signaling

10.7554/elife.22626.018 ◽

2016 ◽

Author(s):

Megan L Norris ◽

Andrea Pauli ◽

James A Gagnon ◽

Nathan D Lord ◽

Katherine W Rogers ◽

...

Keyword(s):

Cell Migration ◽

Author Response ◽

Nodal Signaling ◽

Mesodermal Cell

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Decision letter: Toddler signaling regulates mesodermal cell migration downstream of Nodal signaling

10.7554/elife.22626.017 ◽

2016 ◽

Keyword(s):

Cell Migration ◽

Nodal Signaling ◽

Mesodermal Cell

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Initiation of mesodermal cell migration and spreading relative to gastrulation in the urodele amphibian Pleurodeles waltl

Development ◽

10.1242/dev.105.2.351 ◽

1989 ◽

Vol 105 (2) ◽

pp. 351-363 ◽

Cited By ~ 3

Author(s):

D.-L. Shi ◽

T. Darribere ◽

K.E. Johnson ◽

J.-C. Boucaut

Keyword(s):

Cell Migration ◽

Marginal Zone ◽

Gastrula Stage ◽

Cell Stage ◽

Animal Pole ◽

Mesodermal Cell ◽

Marginal Cells ◽

Pleurodeles Waltl ◽

Early Gastrula

We have investigated the autonomous migration of marginal cells and their interactions with extracellular matrix (ECM) located on the inner surface of the blastocoel roof in the urodele amphibian, Pleurodeles waltl, using a novel in vitro migration assay. Animal hemispheres containing equatorial cells removed at different cleavage stages and dorsal marginal zone (DMZ) explants of early gastrula stage were cultured either on fibronectin (FN)-coated or ECM-conditioned substrata. In explanted animal hemispheres, dorsal marginal cells showed autonomous migration on FN-coated substratum at the same time as the onset of gastrulation in control embryos. They acquired this capacity at least at the 32-cell stage, whereas lateral and ventral marginal cells acquired it after the 64-cell stage. DMZ outgrowths of early gastrula stage exhibited autonomous spreading on both substrata. In addition, we showed that they spread preferentially toward the animal pole when deposited on substratum conditioned by the dorsal roof of the blastocoel. By culturing dissociated marginal cells on ECM- conditioned substratum, we also found that increased spreading capacity of marginal cells was related to the initiation of their migration. A comparative study of the migration of marginal cells in ultraviolet (u.v.)-irradiated and normal embryos was also made. The results indicate that dorsal marginal cell migration was absent or dramatically reduced by u.v.-irradiation. These results suggest that the differential acquisition in the spreading capacity both in timing and in intensity around the marginal zone was correlated with the sequential involution of mesodermal cells in the course of gastrulation.

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Hox10-regulated endodermal cell migration is essential for development of the ascidian intestine

Developmental Biology ◽

10.1016/j.ydbio.2015.03.018 ◽

2015 ◽

Vol 403 (1) ◽

pp. 43-56 ◽

Cited By ~ 18

Author(s):

Narudo Kawai ◽

Yosuke Ogura ◽

Tetsuro Ikuta ◽

Hidetoshi Saiga ◽

Mayuko Hamada ◽

...

Keyword(s):

Cell Migration ◽

Endodermal Cell

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Conditioning of a culture substratum by the ectodermal layer promotes attachment and oriented locomotion by amphibian gastrula mesodermal cells

Journal of Cell Science ◽

10.1242/jcs.59.1.43 ◽

1983 ◽

Vol 59 (1) ◽

pp. 43-60 ◽

Cited By ~ 1

Author(s):

N. Nakatsuji ◽

K.E. Johnson

Keyword(s):

Cell Migration ◽

Time Lapse ◽

Ambystoma Maculatum ◽

Specific Cell ◽

Animal Pole ◽

Micron Diameter ◽

The Relationship ◽

Extracellular Fibrils ◽

Scanning Electron

We have found that ectodermal fragments of Ambystoma maculatum gastrulae deposit immense numbers of 0.1 micron diameter extracellular fibrils on plastic coverslips. When migrating mesodermal cells from A. maculatum gastrulae are seeded on such conditioned plastic substrata, they attach and begin migrating after 15–30 min in vitro. We did a detailed analysis of the relationship between fibril orientation and cell migration using time-lapse cinemicrography, scanning electron microscopy, and a microcomputer with a graphics tablet and morphometric program. We found that cells move in directions closely related to the orientation of fibrils. Usually fibrils are oriented in dense arrays with a predominance of fibrils running parallel to the blastopore-animal pole axis of the explant, and cells move preferentially along lines parallel to the blastopore-animal pole axis. When fibrils are unaligned, cells move at random. We have also shown that cells move with a slightly stronger tendency towards the animal pole direction. These results are discussed concerning the mechanism of specific cell migration during amphibian gastrulation.

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Mesodermal cell migration during Xenopus gastrulation

Developmental Biology ◽

10.1016/0012-1606(90)90159-g ◽

1990 ◽

Vol 142 (1) ◽

pp. 155-168 ◽

Cited By ~ 101

Author(s):

Rudolf Winklbauer

Keyword(s):

Cell Migration ◽

Mesodermal Cell

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Regulation of endodermal cell migration by Rac1 during zebrafish gastrulation

Developmental Biology ◽

10.1016/j.ydbio.2010.05.235 ◽

2010 ◽

Vol 344 (1) ◽

pp. 472

Author(s):

Stephanie Woo ◽

Didier Y. Stainier

Keyword(s):

Cell Migration ◽

Endodermal Cell

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A normally attractive cell interaction is repulsive in two C. elegans mesodermal cell migration mutants

Development ◽

10.1242/dev.113.3.797 ◽

1991 ◽

Vol 113 (3) ◽

pp. 797-803 ◽

Cited By ~ 4

Author(s):

M.J. Stern ◽

H.R. Horvitz

Keyword(s):

Cell Migration ◽

Caenorhabditis Elegans ◽

Premature Termination ◽

Cell Interaction ◽

Egg Laying ◽

Wild Type ◽

Mesodermal Cell ◽

C Elegans ◽

Somatic Gonad ◽

Sex Myoblasts

In wild-type Caenorhabditis elegans hermaphrodites, two bilaterally symmetric sex myoblasts (SMs) migrate anteriorly to flank the precise center of the gonad, where they divide to generate the muscles required for egg laying (J. E. Sulston and H. R. Horvitz (1977) Devl Biol. 56, 110–156). Although this migration is largely independent of the gonad, a signal from the gonad attracts the SMs to their precise final positions (J. H. Thomas, M. J. Stern and H. R. Horvitz (1990) Cell 62, 1041–1052). Here we show that mutations in either of two genes, egl-15 and egl-17, cause the premature termination of the migrations of the SMs. This incomplete migration is caused by the repulsion of the SMs by the same cells in the somatic gonad that are the source of the attractive signal in wild-type animals.

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