A mutant with bilateral whisker to barrel inputs unveils somatosensory mapping rules in the cerebral cortex
- Hôpital de la Pitié-Salpétrière, France
- Sorbonne Universités, UPMC Univ Paris 06, INSERM, CNRS, France
- University of Maryland School of Medicine, United States
- University of Konstanz, Germany
- Friedrich Miescher Institute for Biomedical Research, Switzerland
- INSERM, U839, Institut du Fer à Moulin, France
Abstract
In mammals, tactile information is mapped topographically onto the contralateral side of the brain in the primary somatosensory cortex (S1). Here we describe that in Robo3 mouse mutants a sizeable fraction of the trigemino-thalamic inputs project ipsilaterally rather than contralaterally. The resulting mixture of crossed and uncrossed sensory inputs creates bilateral whisker maps in the thalamus and cortex. Surprisingly, these maps are segregated resulting in a duplication of whisker representations and a doubling of the number of barrels without changes of the S1 size. Sensory deprivation shows competitive interactions between the ipsi/contralateral whisker maps. This study reveals that the somatosensory system can form a somatotopic map to integrate bilateral sensory inputs but organizes the maps in a different way than in the visual, or auditory systems. Therefore, while the molecular pre-patterning constrains their orientation and position, the preservation of the continuity of inputs defines the layout of the somatosensory maps.
Article and author information
Author details
Claudius F Kratochwil
Funding
Agence Nationale de la Recherche (ANR-08-MNP-030,ANR-08,MNP-032,ANR-14-CE13-0004-01,ANR-10-LABX-65)
- Filippo M Rijli
- Patricia Gaspar
- Alain Chédotal
Fondation pour la Recherche Médicale (DEQ20120323700)
- Alain Chédotal
National Institute of Neurological Disorders and Stroke (RO1 NS039050)
- Reha S Erzurumlu
swiss national science foundation (CRSI33_127440)
- Filippo M Rijli
Association Française contre les Myopathies
- Nicolas Renier
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Carol A Mason, Columbia University, United States
Ethics
Animal experimentation: All animal procedures were carried out in accordance to institutional guidelines and approved by the UPMC University ethic committee (ComitÃ{copyright, serif} Charles Darwin, authorization # 03787.02). All surgery was performed under ketamine/xylazine anesthesia, and every effort was made to minimize suffering.
Version history
- Received: November 21, 2016
- Accepted: March 27, 2017
- Accepted Manuscript published: March 28, 2017 (version 1)
- Accepted Manuscript updated: April 3, 2017 (version 2)
- Version of Record published: April 25, 2017 (version 3)
Copyright
© 2017, Renier 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
-
- 2,989
- views
-
- 722
- downloads
-
- 22
- 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)
A mutant with bilateral whisker to barrel inputs unveils somatosensory mapping rules in the cerebral cortex
eLife 6:e23494.
https://doi.org/10.7554/eLife.23494
Further reading
-
- Developmental Biology
Precise developmental timing control is essential for organism formation and function, but its mechanisms are unclear. In C. elegans, the microRNA lin-4 critically regulates developmental timing by post-transcriptionally downregulating the larval-stage-fate controller LIN-14. However, the mechanisms triggering the activation of lin-4 expression toward the end of the first larval stage remain unknown. We demonstrate that the transmembrane transcription factor MYRF-1 is necessary for lin-4 activation. MYRF-1 is initially localized on the cell membrane, and its increased cleavage and nuclear accumulation coincide with lin-4 expression timing. MYRF-1 regulates lin-4 expression cell-autonomously and hyperactive MYRF-1 can prematurely drive lin-4 expression in embryos and young first-stage larvae. The tandem lin-4 promoter DNA recruits MYRF-1GFP to form visible loci in the nucleus, suggesting that MYRF-1 directly binds to the lin-4 promoter. Our findings identify a crucial link in understanding developmental timing regulation and establish MYRF-1 as a key regulator of lin-4 expression.
-
- Developmental Biology
- Structural Biology and Molecular Biophysics
The receptor tyrosine kinase ROR2 mediates noncanonical WNT5A signaling to orchestrate tissue morphogenetic processes, and dysfunction of the pathway causes Robinow syndrome, brachydactyly B, and metastatic diseases. The domain(s) and mechanisms required for ROR2 function, however, remain unclear. We solved the crystal structure of the extracellular cysteine-rich (CRD) and Kringle (Kr) domains of ROR2 and found that, unlike other CRDs, the ROR2 CRD lacks the signature hydrophobic pocket that binds lipids/lipid-modified proteins, such as WNTs, suggesting a novel mechanism of ligand reception. Functionally, we showed that the ROR2 CRD, but not other domains, is required and minimally sufficient to promote WNT5A signaling, and Robinow mutations in the CRD and the adjacent Kr impair ROR2 secretion and function. Moreover, using function-activating and -perturbing antibodies against the Frizzled (FZ) family of WNT receptors, we demonstrate the involvement of FZ in WNT5A-ROR signaling. Thus, ROR2 acts via its CRD to potentiate the function of a receptor super-complex that includes FZ to transduce WNT5A signals.
