Close

Hedgehog signaling is required for endomesodermal patterning and germ cell development in Nematostella vectensis

Cheng-Yi Chen, Sean A. McKinney, Lacey R. Ellington, Matthew C. Gibson

Preprint posted on 15 January 2020 https://www.biorxiv.org/content/10.1101/2020.01.15.907238v1

Article now published in eLife at http://dx.doi.org/10.7554/elife.54573

On the (h)edge: the germline precursors of a basal metazoa are induced at the interface between Hedgehog signalling domains

Selected by Paul Gerald L. Sanchez and Stefano Vianello

 

Background

Organisms that reproduce sexually do so by fusion of two specialised cells: sperm and egg (gametes). By carrying genetic information from one generation to the other these cells ensure the maintenance of the species over time. While in some organisms (e.g. plants) gametes are derived from cells that also give rise to body types, in (most) animals this is not the case. Sperm and eggs are instead produced by a dedicated line of cells put aside very early as to spare them from the accumulation of mutations over time. Throughout reproductive life gametes will be produced by dedicated, germline, stem cells. In turn, these cells have their origin in the embryo and ultimately descend from so-called Primordial Germ Cells (PGCs). 

As the early setting aside of PGCs will ultimately originate the germline, PGC specification is a milestone of early development, and understanding the mechanisms leading to their specification is an area of great interest. Comprehensive surveys of PGC specification across the evolutionary tree report two main strategies through which embryos specify their PGCs:

  • preformation, whereby maternal factors are quickly deposited within a subset of cells in the embryo to lock them into PGC fate
  • induction, whereby PGCs are specified later by signalling cues from the zygote/embryo itself (e.g.  BMP signalling in mouse)

Most model organisms such as C.elegans (roundworm), Drosophila (fruitfly), zebrafish, and Xenopus (frog) all specify their PGCs by preformation, while induction seems to be an exclusive of e.g. chicken, mouse, and human. While preformation might thus intuitively appear to be “ancestral”, most species actually specify PGCs by inductive mechanisms.  Even more interestingly, research on cnidarians (sister group of all bilaterians) has found that here too PGCs are induced rather than locked away by early maternal determinants. The common ancestor of all animals would thus induce their PGCs, but how this actually takes place has remained a mystery.

 

Key Findings

The authors identify the mechanisms of PGC specification in the sea anemone Nematostella vectensis (bilaterian sister group), and confirm that here too specification occurs by induction rather than preformation. Specifically, PGCs are induced out of a field of endomesodermal cells (which surround the pharynx), where these cells abut the ectoderm of the pharynx itself. As can be seen in Figure A, this interface and site of PGC specification crucially coincides with the interface between Hedgehog-signalling domains (Hh and its receptor, Patched).

FIGURE A.

Hedgehog-signaling expression domains, showing juxtaposed expression of the ligand (hh1) and its receptor (ptc). Putative PGC clusters, marked by the Vasa2 protein, form at the interface of the two expression domains. [Modified from Figure 5 of the preprint. Red was changed to magenta using the “Replace Red with Magenta” plug-in in Fiji.]

While maternally inherited germline-determinants (e.g. Vasa2) are indeed detected, these do not differentially accumulate in any cell, and germline transcripts are expressed homogeneously throughout the entire endomesodermal field. Instead, one observes clear segregation between cells expressing the signalling molecule Hedgehog (the pharynx ectoderm), and cells expressing its receptor Patched (the surrounding endomesoderm). At the interface between these domains, where Hedgehog signalling is thus productive, PGCs are specified.

The authors then track these cells as they delaminate out of the endomesoderm by epithelial to mesenchymal transition (EMT)-like mechanisms, and reach the developing gonad rudiments, in which they will mature to germline stem cells.

Results are particularly interesting in the use of Hox mutants, altered in their body plan, where PGCs specify in altered locations (Figure B), indicative of an inductive mode of specification. That is, even though these mutants miss the primary structures where PGCs would be expected to emerge (primary mesenteries), PGCs emerge nonetheless,  if in an altered location. Conversely, even in the wild-type body plan, PGCs will not get specified if Hedgehog signalling is absent (CRISPR experiments).

FIGURE B.

Localization of putative PGC clusters in Hox mutants with altered body plans. [Figure S7 of the preprint. Red was changed to magenta using the “Replace Red with Magenta” plug-in in Fiji.]

 

Significance

The current study builds on the beautiful body of previous work that has investigated the formation of precursor germ cells in a basal metazoa, Nematostella vectensis. The authors provide here several pieces of evidence supporting inductive PGC specification (versus preformation) as an ancestral strategy in eumetazoans, and they capitalize on experimental advances that were not previously available (e.g. immunostaining with antibody against Vasa2 and generation of mutants using CRISPR/Cas9).

The identification of the role of Hedgehog signaling in specification of PGCs is remarkable and sparks interesting developmental questions. Most noteworthy is the description of the reciprocal expression of the Hedgehog ligand and its receptor, and how putative PGCs (Vasa2+ cells) form at the interface of these juxtaposed expression domains. 

The preprint provides thought-provoking mechanistic insight into the possible earliest forms of animal PGC specification.

 

Questions to the authors:

  • What is known about the role of Hedgehog signalling for PGC induction in other organisms and model systems? Are there traces (or conservation) of such ancestral evolutionary strategy?
  • Would it be possible to implant a bead with Hh ligand (hh1) in the endomesoderm of the planula, adjacent to the domain expressing the Hh receptor (ptc)? Would this result in specification of an ectopic putative PGC cluster?
  • BMP signalling is described here as having a purely attractive/repulsive role, almost like a chemokine. This is in contrast with its key PGC-inductive role usually associated to it based on studies in e.g. mouse (and even cricket, cfr. Extavour and Nakamura 2016). Could you elaborate on this?
  • It is particularly remarkable that PGCs form near the mouth in Nematostella, while their site of induction is posterior in mouse (and human?). Could a model be made whereby the site of PGC specification correlates with the site of Gastrulation?
  • If zygotic specification is ancestral, what would be the model explaining loss of this strategy in favour of determinant deposition (preformation) in some later species?

 

Further Reading

  • Extavour, Cassandra G., and Michael Akam. “Mechanisms of germ cell specification across the metazoans: epigenesis and preformation.” Development 130.24 (2003): 5869-5884.
  • Extavour, Cassandra G., et al. “Vasa and nanos expression patterns in a sea anemone and the evolution of bilaterian germ cell specification mechanisms.” Evolution & development 7.3 (2005): 201-215.
  • Johnson, Andrew D., and Ramiro Alberio. “Primordial germ cells: the first cell lineage or the last cells standing?.” Development 142.16 (2015): 2730-2739.
  • He, Shuonan, et al. “An axial Hox code controls tissue segmentation and body patterning in Nematostella vectensis.” Science 361.6409 (2018): 1377-1380.
  • Matus, David Q., et al. “The Hedgehog gene family of the cnidarian, Nematostella vectensis, and implications for understanding metazoan Hedgehog pathway evolution.” Developmental biology 313.2 (2008): 501-518.

Tags: hh, nematostella, pgc, primordial germ cells

Posted on: 25 February 2020

doi: https://doi.org/10.1242/prelights.16775

Read preprint (1 votes)

Have your say

Your email address will not be published.

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

preLists in the developmental biology category:

2nd Conference of the Visegrád Group Society for Developmental Biology

Preprints from the 2nd Conference of the Visegrád Group Society for Developmental Biology (2-5 September, 2021, Szeged, Hungary)

 



List by Nándor Lipták

Fibroblasts

The advances in fibroblast biology preList explores the recent discoveries and preprints of the fibroblast world. Get ready to immerse yourself with this list created for fibroblasts aficionados and lovers, and beyond. Here, my goal is to include preprints of fibroblast biology, heterogeneity, fate, extracellular matrix, behavior, topography, single-cell atlases, spatial transcriptomics, and their matrix!

 



List by Osvaldo Contreras

EMBL Synthetic Morphogenesis: From Gene Circuits to Tissue Architecture (2021)

A list of preprints mentioned at the #EESmorphoG virtual meeting in 2021.

 



List by Alex Eve

EMBL Conference: From functional genomics to systems biology

Preprints presented at the virtual EMBL conference "from functional genomics and systems biology", 16-19 November 2020

 



List by Jesus Victorino

Single Cell Biology 2020

A list of preprints mentioned at the Wellcome Genome Campus Single Cell Biology 2020 meeting.

 



List by Alex Eve

Society for Developmental Biology 79th Annual Meeting

Preprints at SDB 2020

 



List by Irepan Salvador-Martinez, Martin Estermann

FENS 2020

A collection of preprints presented during the virtual meeting of the Federation of European Neuroscience Societies (FENS) in 2020

 



List by Ana Dorrego-Rivas

Planar Cell Polarity – PCP

This preList contains preprints about the latest findings on Planar Cell Polarity (PCP) in various model organisms at the molecular, cellular and tissue levels.

 



List by Ana Dorrego-Rivas

Cell Polarity

Recent research from the field of cell polarity is summarized in this list of preprints. It comprises of studies focusing on various forms of cell polarity ranging from epithelial polarity, planar cell polarity to front-to-rear polarity.

 



List by Yamini Ravichandran

TAGC 2020

Preprints recently presented at the virtual Allied Genetics Conference, April 22-26, 2020. #TAGC20

 



List by Maiko Kitaoka et al.

3D Gastruloids

A curated list of preprints related to Gastruloids (in vitro models of early development obtained by 3D aggregation of embryonic cells). Updated until July 2021.

 



List by Paul Gerald L. Sanchez and Stefano Vianello

ASCB EMBO Annual Meeting 2019

A collection of preprints presented at the 2019 ASCB EMBO Meeting in Washington, DC (December 7-11)

 



List by Madhuja Samaddar et al.

EDBC Alicante 2019

Preprints presented at the European Developmental Biology Congress (EDBC) in Alicante, October 23-26 2019.

 



List by Sergio Menchero et al.

EMBL Seeing is Believing – Imaging the Molecular Processes of Life

Preprints discussed at the 2019 edition of Seeing is Believing, at EMBL Heidelberg from the 9th-12th October 2019

 



List by Dey Lab

SDB 78th Annual Meeting 2019

A curation of the preprints presented at the SDB meeting in Boston, July 26-30 2019. The preList will be updated throughout the duration of the meeting.

 



List by Alex Eve

Lung Disease and Regeneration

This preprint list compiles highlights from the field of lung biology.

 



List by Rob Hynds

Young Embryologist Network Conference 2019

Preprints presented at the Young Embryologist Network 2019 conference, 13 May, The Francis Crick Institute, London

 



List by Alex Eve

Pattern formation during development

The aim of this preList is to integrate results about the mechanisms that govern patterning during development, from genes implicated in the processes to theoritical models of pattern formation in nature.

 



List by Alexa Sadier

BSCB/BSDB Annual Meeting 2019

Preprints presented at the BSCB/BSDB Annual Meeting 2019

 



List by Dey Lab

Zebrafish immunology

A compilation of cutting-edge research that uses the zebrafish as a model system to elucidate novel immunological mechanisms in health and disease.

 



List by Shikha Nayar

Also in the evolutionary biology category:

Close