Close

Timed collinear activation of Hox genes during gastrulation controls the avian forelimb position

Chloe Moreau, Paolo Caldarelli, Didier Rocancourt, Julian Roussel, Nicolas Denans, Olivier Pourquie, Jerome Gros

Posted on: 27 June 2018

Preprint posted on 20 June 2018

Article now published in Current Biology at http://dx.doi.org/10.1016/j.cub.2018.11.009

Positioning of the limb field was long suspected to be dependent on Hox activity. Moreau et al. show for the first time that in avian species limb field positioning is dependent on Hox collinear activation during early gastrulation.

Selected by Wouter Masselink

Background

The formation of paired appendages in general, and limbs specifically is a crucial adaptation, which provides mobility to animals. The correct positioning of the limbs along the AP axis is essential for a robust body plan and any deviation severely impedes the mobility of an animal. As such, while remarkable variation exists in the positioning of the limb across species, their position is highly robust within any given species. The positioning of limb outgrowth correlates with specific regions of the spine. The spine can generally be divided into 4 regions; cervical, thoracic, lumbar, and sacral. Across tetrapods forelimb outgrowth occurs at the level of the cervico-thoracic boundary, while hindlimb outgrowth occurs at the level of the lumbo-sacral boundary. It is well understood that AP identity is provided by the phenomenon of Hox collinearity and as such directly controls vertebral identity. Therefore, Hox collinearity was long suspected to instruct the positioning of limb fields ( for reviews see Tanaka 2013, Tanaka 2016, Tickle 2015) but was never formally shown. Now for the first time, Chloe Moreau and colleagues combine classical comparative anatomy with advanced over-expression studies to provide direct evidence that Hox code identities instruct limb field positioning.

 

Key findings

In their preprint Moreau and colleagues use classical chicken embryological studies to find that the position of the forelimb bud is already specified by the end of gastrulation. They took advantage of the tissue grafting amenability of the chicken and show that a forelimb region grafted in an inter-limb position (and vice versa) results in the limb bud appearing in an interlimb position. Specifically, HoxB4, HoxB7, and HoxB9 were identified to be sequentially expressed in the epiblast as the forelimb position is specified. The activation of HoxB4 and inhibition of HoxB9 was sufficient to induce a limb field in the inter-limb region. These data suggest that HoxB4 and HoxB9 act together to specify the position of the fore-limb in chicken embryos.

 

If this was indeed true, this should be conserved across species. While mammals show very little variability in the positioning of the fore limb, in birds there is significant variability. Chickens consistently form their limbs at the 15th vertebra, while zebra finches and ostriches do so at the 13th and 18th vertebra, respectively. Taking advantage of this fact, it was expected that Hoxb4 and Hoxb9 expression is shifted anteriorly in zebra finches and posteriorly in Ostriches. Indeed, Hoxb4/Hoxb9 boundaries are shifted and this is consistent with the specification of the limb field.

 

In a final heroic effort, the authors attempted to shift the boundary of Hoxb4/Hoxb9 expression by modulation of retinoic acid (RA) activity. The RA metabolizing enzyme, Cyp26a1, is known to modulate Hox gene activities. Cyp26a1 has variable expression domains in chicken, zebra finch and ostrich consistent with their variable specification of the forelimb. Indeed, the authors found that modulating RA activity, by either supplying exogenous RA or an RA antagonist shifts the Hoxb4/Hoxb9 boundary. Consistent with the observations made in ostrich and zebra finch embryos exogenous RA shifts the Hoxb4/Hoxb9 boundary and the subsequent limb field posteriorly. Conversely, the inhibition of RA activity results in a posterior shift of the Hoxb4/Hoxb9 boundary and the associated limb field.

 

Taken together the authors convincingly show that the activation of Hoxb4 and repression of Hoxb9 are sufficient to induce the formation of the forelimb field and are responsible for the variability observed across bird species.

 

What I like about this work

This work takes advantage of the natural variability seen in the limb positioning of avian species. The authors use this variability to validate a long-suspected mechanism. The work is done rigorously showing both necessity and sufficiency, through several independent lines of work. Like any good piece of research, it answers one question while opening up several more.

 

Outlook

While the authors convincingly show how the expression domains of Hoxb4 and Hoxb9 specify the Tbx5 positive limb field, and thus specifies the position of the future limb. It makes me wonder if the authors attempted more longitudinal studies to see whether a shifting limb field also changes further downstream processes such as skeleton formation and nerve innervation. Also, is this a general mechanism which applies across all species with paired appendages or is it restricted to avian species or tetrapods? Given that Hox collinearity is an ancient patterning mechanism also seen in insects and jawless vertebrates, I would suspect that appendages in general is likely dependent on similar mechanisms and should thus also apply to both bony and cartilaginous fish. As such it would be interesting to see if the findings reported here also apply to skates. Skates are members of the cartilaginous fish family and have dramatically enlarged pectoral fins. If a similar mechanism applies in specifying the pectoral fin field in skates, one would expect a relative expansion of the hoxb4 domain, while Hoxb9 should be shifted further posteriorly. This should result in a wider fin bud allowing for the subsequent expansion of the pectoral fin domain.

 

References

  1. Tanaka, M. (2013). Molecular and evolutionary basis of limb field specification and limb initiation. Dev. Growth Differ. 55, 149–163.
  2. Tanaka, M. (2016). Developmental Mechanism of Limb Field Specification along the Anterior–Posterior Axis during Vertebrate Evolution. J. Dev. Biol. 4, 18.
  3. Tickle, C. (2015). How the embryo makes a limb: determination, polarity and identity. J. Anat. 227, 418–430.

Tags: chicken, hox, limb, positional identity

Read preprint (No Ratings Yet)

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 developmental biology category:

Specialized signaling centers direct cell fate and spatial organization in a limb organoid model

Evangelia Skoufa, Jixing Zhong, Oliver Kahre, et al.

Selected by 05 September 2024

Ryan Harrison

Developmental Biology

Adult caudal fin shape is imprinted in the embryonic fin fold

Eric Surette, Joan Donahue, Stephanie Robinson, et al.

Selected by 28 August 2024

Isabella Cisneros

Developmental Biology

TAK1 operates at the primary cilium in non-canonical TGFB/BMP signaling to control heart development

Canan Doganli, Daniel A. Baird, Yeasmeen Ali, et al.

Selected by 16 August 2024

Reinier Prosee

Developmental Biology

Also in the evolutionary biology category:

Enhancer-driven cell type comparison reveals similarities between the mammalian and bird pallium

Nikolai Hecker , Niklas Kempynck , David Mauduit, et al.

Selected by 02 July 2024

Rodrigo Senovilla-Ganzo

Bioinformatics

Modular control of time and space during vertebrate axis segmentation

Ali Seleit, Ian Brettell, Tomas Fitzgerald, et al.

AND

Natural genetic variation quantitatively regulates heart rate and dimension

Jakob Gierten, Bettina Welz, Tomas Fitzgerald, et al.

Selected by 24 June 2024

Girish Kale, Jennifer Ann Black

Developmental Biology

Fetal brain response to maternal inflammation requires microglia

Bridget Elaine LaMonica Ostrem, Nuria Dominguez Iturza, Jeffrey Stogsdill, et al.

Selected by 24 April 2024

Manuel Lessi

Neuroscience

preLists in the developmental biology category:

BSDB/GenSoc Spring Meeting 2024

A list of preprints highlighted at the British Society for Developmental Biology and Genetics Society joint Spring meeting 2024 at Warwick, UK.

 



List by Joyce Yu, Katherine Brown

GfE/ DSDB meeting 2024

This preList highlights the preprints discussed at the 2024 joint German and Dutch developmental biology societies meeting that took place in March 2024 in Osnabrück, Germany.

 



List by Joyce Yu

‘In preprints’ from Development 2022-2023

A list of the preprints featured in Development's 'In preprints' articles between 2022-2023

 



List by Alex Eve, Katherine Brown

preLights peer support – preprints of interest

This is a preprint repository to organise the preprints and preLights covered through the 'preLights peer support' initiative.

 



List by preLights peer support

The Society for Developmental Biology 82nd Annual Meeting

This preList is made up of the preprints discussed during the Society for Developmental Biology 82nd Annual Meeting that took place in Chicago in July 2023.

 



List by Joyce Yu, Katherine Brown

CSHL 87th Symposium: Stem Cells

Preprints mentioned by speakers at the #CSHLsymp23

 



List by Alex Eve

Journal of Cell Science meeting ‘Imaging Cell Dynamics’

This preList highlights the preprints discussed at the JCS meeting 'Imaging Cell Dynamics'. The meeting was held from 14 - 17 May 2023 in Lisbon, Portugal and was organised by Erika Holzbaur, Jennifer Lippincott-Schwartz, Rob Parton and Michael Way.

 



List by Helen Zenner

9th International Symposium on the Biology of Vertebrate Sex Determination

This preList contains preprints discussed during the 9th International Symposium on the Biology of Vertebrate Sex Determination. This conference was held in Kona, Hawaii from April 17th to 21st 2023.

 



List by Martin Estermann

Alumni picks – preLights 5th Birthday

This preList contains preprints that were picked and highlighted by preLights Alumni - an initiative that was set up to mark preLights 5th birthday. More entries will follow throughout February and March 2023.

 



List by Sergio Menchero et al.

CellBio 2022 – An ASCB/EMBO Meeting

This preLists features preprints that were discussed and presented during the CellBio 2022 meeting in Washington, DC in December 2022.

 



List by Nadja Hümpfer et al.

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:

‘In preprints’ from Development 2022-2023

A list of the preprints featured in Development's 'In preprints' articles between 2022-2023

 



List by Alex Eve, Katherine Brown

preLights peer support – preprints of interest

This is a preprint repository to organise the preprints and preLights covered through the 'preLights peer support' initiative.

 



List by preLights peer support

EMBO | EMBL Symposium: The organism and its environment

This preList contains preprints discussed during the 'EMBO | EMBL Symposium: The organism and its environment', organised at EMBL Heidelberg, Germany (May 2023).

 



List by Girish Kale

9th International Symposium on the Biology of Vertebrate Sex Determination

This preList contains preprints discussed during the 9th International Symposium on the Biology of Vertebrate Sex Determination. This conference was held in Kona, Hawaii from April 17th to 21st 2023.

 



List by Martin Estermann

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

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

TAGC 2020

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

 



List by Maiko Kitaoka et al.

ECFG15 – Fungal biology

Preprints presented at 15th European Conference on Fungal Genetics 17-20 February 2020 Rome

 



List by Hiral Shah

COVID-19 / SARS-CoV-2 preprints

List of important preprints dealing with the ongoing coronavirus outbreak. See http://covidpreprints.com for additional resources and timeline, and https://connect.biorxiv.org/relate/content/181 for full list of bioRxiv and medRxiv preprints on this topic

 



List by Dey Lab, Zhang-He Goh

1

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

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
Close