Cell-nonautonomous local and systemic responses to cell arrest enable long-bone catch-up growth

Alberto Rosello-Diez, Linda Madisen, Sebastien Bastide, Hongkui Zeng, Alexandra L Joyner

Preprint posted on December 23, 2017

How is symmetric growth of paired limbs maintained in the mouse embryo? Partial arrest of proliferation in one limb induces local compensatory proliferation and global reduction in body size.

Selected by Anna Kicheva

Categories: developmental biology


Lewis Wolpert, among others, has noted that it is remarkable how paired organs, such as the limbs, grow in precise symmetry (see Even more remarkable is that this coordination is restored upon unilateral growth insult of the limb, so that the left and right limbs end up with similar sizes at birth. The study of Alberto Rosello-Diez, Alexandra Joyner and colleagues provides new insight into how this happens.

Key results

The authors use a clever genetic approach to arrest cell proliferation of a fraction of chrondrocytes within the left limb of mouse embryos. This caused compensatory overproliferation of the non-arrested neighboring chrondrocytes. Remarkably, this perturbation also affected growth of the rest of the body, causing the right limb to become 10% smaller than in control embryos. Thus, both intrinsic and extrinsic mechanisms regulate limb growth. The approach opens a new way forward to investigating what these mechanisms are at the molecular level. The authors link the limb-intrinsic compensation to sensing cell density within the growth plate, and the systemic effect – to IGF secreted by the placenta.

Open questions

Further studies will be needed to find out: what is the “alarm” signal sent by the perturbed limb? Is the same signal involved in the intrinsic and systemic mechanisms? How do mechanical vs biochemical signals contribute to proliferation control in this system?


preLighter Natalie Dye has also highlighted this preprint – check out her highlight here.


Read preprint (No Ratings Yet)

  • Have your say

    Your email address will not be published.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

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

    Register here

    Also in the developmental biology category:

    Long-term live imaging of the Drosophila adult midgut reveals real-time dynamics of cell division, differentiation, and loss

    Judy Martin, Erin Nicole Sanders, Paola Moreno-Roman, et al.

    Selected by Natalie Dye

    From spiral cleavage to bilateral symmetry: The developmental cell lineage of the annelid brain

    Pavel Vopalensky, Maria Antonietta Tosches, Kaia Achim, et al.

    Selected by Erik Clark

    A 3D model of human skeletal muscle innervated with stem cell-derived motor neurons enables epsilon-subunit targeted myasthenic syndrome studies

    Mohsen Afshar Bakooshli, Ethan S Lippmann, Ben Mulcahy, et al.

    Selected by Chris Demers

    Lineage tracing axial progenitors using Nkx1.2CreERT2 mice defines their trunk and tail contributions

    Aida Rodrigo Albors, Pamela A Halley, Kate G Storey

    Selected by Pierre Osteil

    Feedback control of neurogenesis by tissue packing

    Tom W. Hiscock, Joel B. Miesfeld, Kishore R. Mosaliganti, et al.

    Selected by Sarah Morson


    Focal adhesion kinase regulates early steps of myofibrillogenesis in cardiomyocytes

    Nilay Taneja, Abigail C Neininger, Matthew R Bersi, et al.

    Selected by Vassilis Papalazarou

    Content-Aware Image Restoration: Pushing the Limits of Fluorescence Microscopy

    Martin Weigert, Uwe Schmidt, Tobias Boothe, et al.

    Selected by Uri Manor

    In vivo topology converts competition for cell-matrix adhesion into directional migration

    Fernanda Bajanca, Nadege Gouignard, Charlotte Colle, et al.

    Selected by Helen Zenner

    The expa1-1 mutant reveals a new biophysical lateral root organogenesis checkpoint

    Priya Ramakrishna, Graham A. Rance, Lam D. Vu, et al.

    Selected by Annika Weimer


    F-actin patches nucleated on chromosomes coordinate capture by microtubules in oocyte meiosis

    Mariia Burdyniuk, Andrea Callegari, Masashi Mori, et al.

    Selected by Binyam Mogessie

    Polarization of Myosin II refines tissue material properties to buffer mechanical stress.

    Maria Duda, Nargess Khalilgharibi, Nicolas Carpi, et al.

    Selected by Yara E. Sánchez Corrales

    Cell-nonautonomous local and systemic responses to cell arrest enable long-bone catch-up growth

    Alberto Rosello-Diez, Linda Madisen, Sebastien Bastide, et al.

    Selected by Natalie Dye

    An Epiblast Stem Cell derived multipotent progenitor population for axial extension

    Shlomit Edri, Penelope Hayward, Peter Baillie-Johnson, et al.

    Selected by Pierre Osteil


    The Trithorax group protein dMLL3/4 instructs the assembly of the zygotic genome at fertilization

    Pedro Prudêncio, Leonardo G. Guilgur, João Sobral, et al.

    Selected by Carmen Adriaens

    Observing the Cell in Its Native State: Imaging Subcellular Dynamics in Multicellular Organisms

    Tsung-li Liu, Srigokul Upadhyayula, Daniel E Milkie, et al.

    Selected by Arnaud Monnard, Gautam Dey

    Precise temporal regulation of alternative splicing during neural development

    Sebastien M Weyn-Vanhentenryck, Huijuan Feng, Dmytro Ustianenko, et al.

    Selected by James Gagnon

    We want to make our website, and the services we provide, useful and reliable. This sometimes involves placing small amounts of information called cookies on the device you used to access the internet. If you continue to use this website we will assume you are happy to accept our cookies.