Genetic mechanisms control the linear scaling between related cortical primary and higher order sensory areas

  1. Andreas Zembrzycki  Is a corresponding author
  2. Adam M Stocker
  3. Axel Leingärtner
  4. Setsuko Sahara
  5. Shen-Ju Chou
  6. Valery Kalatsky
  7. Scott R May
  8. Michael P Stryker
  9. Dennis DM O'Leary
  1. The Salk Institute For Biological Studies, United States
  2. Minnesota State University Moorhead, United States
  3. University Medical Center, Germany
  4. King's College London, United Kingdom
  5. Academia Sinica, Taiwan
  6. Enthought Scientific Computing Solutions, United States
  7. University of California, San Francisco, United States

Abstract

In mammals, the neocortical layout consists of few modality-specific primary sensory areas and a multitude of higher order ones. Abnormal layout of cortical areas may disrupt sensory function and behavior. Developmental genetic mechanisms specify primary areas, but mechanisms influencing higher order area properties are unknown. By exploiting gain-of and loss-of function mouse models of the transcription factor Emx2, we have generated bi-directional changes in primary visual cortex size in vivo and have used it as a model to show a novel and prominent function for genetic mechanisms regulating primary visual area size and also proportionally dictating the sizes of surrounding higher order visual areas. This finding redefines the role for intrinsic genetic mechanisms to concomitantly specify and scale primary and related higher order sensory areas in a linear fashion.

Article and author information

Author details

  1. Andreas Zembrzycki

    Molecular Neurobiology Laboratory, The Salk Institute For Biological Studies, La Jolla, United States
    For correspondence
    azembrzycki@salk.edu
    Competing interests
    The authors declare that no competing interests exist.
  2. Adam M Stocker

    Biosciences Department, Minnesota State University Moorhead, Moorhead, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Axel Leingärtner

    University Cancer Center Hamburg, University Medical Center, Hamburg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  4. Setsuko Sahara

    MRC Centre for Developmental Neurobiology, King's College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  5. Shen-Ju Chou

    Institute of Cellular and Organismic Biology, Academia Sinica, Taipei, Taiwan
    Competing interests
    The authors declare that no competing interests exist.
  6. Valery Kalatsky

    Enthought Scientific Computing Solutions, Austin, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Scott R May

    Molecular Neurobiology Laboratory, The Salk Institute For Biological Studies, La Jolla, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Michael P Stryker

    Center for Integrative Neuroscience, Department of Physiology, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Dennis DM O'Leary

    Molecular Neurobiology Laboratory, The Salk Institute For Biological Studies, La Jolla, United States
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. Moses V Chao, New York University School of Medicine, United States

Ethics

Animal experimentation: All experiments were approved under Protocol #09-012 and conducted following the guidelines of the Institutional Animal Care and Use Committee at the Salk Institute and were in full compliance with the guidelines of the National Institutes of Health for the care and use of laboratory animals.

Version history

  1. Received: September 5, 2015
  2. Accepted: December 23, 2015
  3. Accepted Manuscript published: December 24, 2015 (version 1)
  4. Version of Record published: January 26, 2016 (version 2)

Copyright

© 2015, Zembrzycki et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 2,198
    views
  • 483
    downloads
  • 13
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Andreas Zembrzycki
  2. Adam M Stocker
  3. Axel Leingärtner
  4. Setsuko Sahara
  5. Shen-Ju Chou
  6. Valery Kalatsky
  7. Scott R May
  8. Michael P Stryker
  9. Dennis DM O'Leary
(2015)
Genetic mechanisms control the linear scaling between related cortical primary and higher order sensory areas
eLife 4:e11416.
https://doi.org/10.7554/eLife.11416

Share this article

https://doi.org/10.7554/eLife.11416

Further reading

    1. Chromosomes and Gene Expression
    2. Developmental Biology
    F Javier DeHaro-Arbona, Charalambos Roussos ... Sarah Bray
    Research Article

    Developmental programming involves the accurate conversion of signalling levels and dynamics to transcriptional outputs. The transcriptional relay in the Notch pathway relies on nuclear complexes containing the co-activator Mastermind (Mam). By tracking these complexes in real time, we reveal that they promote the formation of a dynamic transcription hub in Notch ON nuclei which concentrates key factors including the Mediator CDK module. The composition of the hub is labile and persists after Notch withdrawal conferring a memory that enables rapid reformation. Surprisingly, only a third of Notch ON hubs progress to a state with nascent transcription, which correlates with polymerase II and core Mediator recruitment. This probability is increased by a second signal. The discovery that target-gene transcription is probabilistic has far-reaching implications because it implies that stochastic differences in Notch pathway output can arise downstream of receptor activation.

    1. Developmental Biology
    Rieko Asai, Vivek N Prakash ... Takashi Mikawa
    Research Article

    Large-scale cell flow characterizes gastrulation in animal development. In amniote gastrulation, particularly in avian gastrula, a bilateral vortex-like counter-rotating cell flow, called ‘polonaise movements’, appears along the midline. Here, through experimental manipulations, we addressed relationships between the polonaise movements and morphogenesis of the primitive streak, the earliest midline structure in amniotes. Suppression of the Wnt/planar cell polarity (PCP) signaling pathway maintains the polonaise movements along a deformed primitive streak. Mitotic arrest leads to diminished extension and development of the primitive streak and maintains the early phase of the polonaise movements. Ectopically induced Vg1, an axis-inducing morphogen, generates the polonaise movements, aligned to the induced midline, but disturbs the stereotypical cell flow pattern at the authentic midline. Despite the altered cell flow, induction and extension of the primitive streak are preserved along both authentic and induced midlines. Finally, we show that ectopic axis-inducing morphogen, Vg1, is capable of initiating the polonaise movements without concomitant PS extension under mitotic arrest conditions. These results are consistent with a model wherein primitive streak morphogenesis is required for the maintenance of the polonaise movements, but the polonaise movements are not necessarily responsible for primitive streak morphogenesis. Our data describe a previously undefined relationship between the large-scale cell flow and midline morphogenesis in gastrulation.