Laminin α2 controls mouse and human stem cell behaviour during midbrain dopaminergic neuron development

Development
Maqsood AhmedCharles Ffrench-Constant

Abstract

Development of the central nervous system requires coordination of the proliferation and differentiation of neural stem cells. Here, we show that laminin alpha 2 (lm-α2) is a component of the midbrain dopaminergic neuron (mDA) progenitor niche in the ventral midbrain (VM) and identify a concentration-dependent role for laminin α2β1γ1 (lm211) in regulating mDA progenitor proliferation and survival via a distinct set of receptors. At high concentrations, lm211-rich environments maintain mDA progenitors in a proliferative state via integrins α6β1 and α7β1, whereas low concentrations of lm211 support mDA lineage survival via dystroglycan receptors. We confirmed our findings in vivo, demonstrating that the VM was smaller in the absence of lm-α2, with increased apoptosis; furthermore, the progenitor pool was depleted through premature differentiation, resulting in fewer mDA neurons. Examination of mDA neuron subtype composition showed a reduction in later-born mDA neurons of the ventral tegmental area, which control a range of cognitive behaviours. Our results identify a novel role for laminin in neural development and provide a possible mechanism for autism-like behaviours and the brainstem hypoplasia seen in some individuals with m...Continue Reading

References

Oct 1, 1995·Developmental Dynamics : an Official Publication of the American Association of Anatomists·J N SchofieldY H Edwards
Apr 2, 2004·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Sandra BlaessUlrich Müller
May 11, 2005·Developmental Biology·Lynn BedfordFred Sablitzky
Aug 7, 2007·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Claire AndersonAnne-Gaëlle Borycki
Oct 24, 2007·The Journal of Comparative Neurology·Justin D LathiaCharles ffrench-Constant
Dec 11, 2008·Annals of Neurology·Emma ClementFrancesco Muntoni
Feb 3, 2009·Neuropsychiatric Disease and Treatment·Kenneth BlumMarlene Oscar-Berman
Mar 17, 2009·Nature Neuroscience·Jennifer A ChanRosalind A Segal
Aug 19, 2009·PLoS Biology·Karine LoulierCharles Ffrench-Constant
Oct 27, 2009·Developmental Biology·Tania Rozario, Douglas W DeSimone
May 11, 2010·Cell Stem Cell·Justin D LathiaJeremy N Rich
Jul 28, 2010·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Ilias KazanisCharles ffrench-Constant
Dec 17, 2011·Seminars in Pediatric Neurology·Enrico BertiniStefania Petrini
Jul 4, 2012·Proceedings of the National Academy of Sciences of the United States of America·Simone A FietzWieland B Huttner
Jan 3, 2013·Annals of Neurology·Justin D LathiaJeremy N Rich
Jan 15, 2013·Frontiers in Cellular Neuroscience·Agnete KirkebyMalin Parmar
Apr 16, 2015·Nature Reviews. Neuroscience·David J NuttPaul R A Stokes
May 12, 2015·Nature Neuroscience·Anna KabanovaSandra Blaess
Sep 9, 2015·Nature Communications·Jessica MorgnerSara A Wickström
Sep 26, 2015·Cell·Alex A PollenArnold R Kriegstein
Jun 9, 2016·Nature Neuroscience·Yannick PoitelonMaria Laura Feltri
Aug 23, 2016·Current Stem Cell Reports·Maqsood Ahmed, Charles Ffrench-Constant
Jan 6, 2017·Nature Reviews. Neuroscience·Marisela Morales, Elyssa B Margolis
Jun 13, 2017·Cell Stem Cell·Tobias L HaasRuggero De Maria
Dec 2, 2017·Matrix Biology : Journal of the International Society for Matrix Biology·Peter D YurchencoMarkus A Rüegg
Mar 14, 2018·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Marcos Assis NascimentoTatiana Coelho-Sampaio

❮ Previous
Next ❯

Citations

Aug 28, 2020·Frontiers in Molecular Neuroscience·Anna SarkozyFrancesco Muntoni
Jul 7, 2020·Frontiers in Cell and Developmental Biology·Tiago Cardoso, Martin Lévesque
Aug 15, 2020·Frontiers in Molecular Neuroscience·Andrea J Arreguin, Holly Colognato
Jul 3, 2020·International Journal of Molecular Sciences·Samir Vaid, Wieland B Huttner

❮ Previous
Next ❯

Related Concepts

Related Feeds

Amygdala and Midbrain Dopamine

The midbrain dopamine system is widely studied for its involvement in emotional and motivational behavior. Some of these neurons receive information from the amygdala and project throughout the cortex. When the circuit and transmission of dopamine is disrupted symptoms may present. Here is the latest research on the amygdala and midbrain dopamine.

Researcher Network:CZI Neurodegeneration Challenge

The Neurodegeneration Challenge Network aims to provide funding for and to bring together researchers studying neurodegenerative diseases. Find the latest research from the NDCN grantees here.

Adult Stem Cells

Adult stem cells reside in unique niches that provide vital cues for their survival, self-renewal, and differentiation. They hold great promise for use in tissue repair and regeneration as a novel therapeutic strategies. Here is the latest research.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

Adhesion Molecules in Health and Disease

Cell adhesion molecules are a subset of cell adhesion proteins located on the cell surface involved in binding with other cells or with the extracellular matrix in the process called cell adhesion. In essence, cell adhesion molecules help cells stick to each other and to their surroundings. Cell adhesion is a crucial component in maintaining tissue structure and function. Discover the latest research on adhesion molecule and their role in health and disease here.

Autism

Autism spectrum disorder is associated with challenges with social skills, repetitive behaviors, and often accompanied by sensory sensitivities and medical issues. Here is the latest research on autism.

Related Papers

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
Min YinJiawei Zhou
Proceedings of the National Academy of Sciences of the United States of America
Sangmi ChungKwang-Soo Kim
© 2021 Meta ULC. All rights reserved