scholarly journals Local Translation Across Neural Development: A Focus on Radial Glial Cells, Axons, and Synaptogenesis

2021 ◽  
Vol 14 ◽  
Author(s):  
Manasi Agrawal ◽  
Kristy Welshhans

In the past two decades, significant progress has been made in our understanding of mRNA localization and translation at distal sites in axons and dendrites. The existing literature shows that local translation is regulated in a temporally and spatially restricted manner and is critical throughout embryonic and post-embryonic life. Here, recent key findings about mRNA localization and local translation across the various stages of neural development, including neurogenesis, axon development, and synaptogenesis, are reviewed. In the early stages of development, mRNAs are localized and locally translated in the endfeet of radial glial cells, but much is still unexplored about their functional significance. Recent in vitro and in vivo studies have provided new information about the specific mechanisms regulating local translation during axon development, including growth cone guidance and axon branching. Later in development, localization and translation of mRNAs help mediate the major structural and functional changes that occur in the axon during synaptogenesis. Clinically, changes in local translation across all stages of neural development have important implications for understanding the etiology of several neurological disorders. Herein, local translation and mechanisms regulating this process across developmental stages are compared and discussed in the context of function and dysfunction.

Author(s):  
Louis-Jan Pilaz ◽  
Kaumudi Joshi ◽  
Jing Liu ◽  
Yuji Tsunekawa ◽  
Fernando Alsina ◽  
...  

mRNA localization and local translation enable exquisite spatial and temporal control of gene expression, particularly in highly polarized and elongated cells. These features are especially prominent in radial glial cells (RGCs), which serve as neural and glial precursors of the developing cerebral cortex, and scaffolds for migrating neurons. Yet the mechanisms by which distinct sub-cellular compartments of RGCs accomplish their diverse functions are poorly understood. Here, we demonstrate that subcellular RNA localization and translation of the RhoGAP Arhgap11a controls RGC morphology and mediates cortical cytoarchitecture. Arhgap11a mRNA and protein exhibit conserved localization to RGC basal structures in mice and humans, conferred by a 5′UTR cis-element. Proper RGC morphology relies upon active Arhgap11a mRNA transport and localization to basal structures, where ARHGAP11A is locally synthesized. Thus, RhoA activity is spatially and acutely activated via local translation in RGCs to promote neuron positioning and cortical cytoarchitecture. Altogether, our study demonstrates that mRNA localization and local translation mediate compartmentalization of neural progenitor functions to control brain development.


2014 ◽  
Vol 94 (3) ◽  
pp. 709-737 ◽  
Author(s):  
Leda Dimou ◽  
Magdalena Götz

The diverse functions of glial cells prompt the question to which extent specific subtypes may be devoted to a specific function. We discuss this by reviewing one of the most recently discovered roles of glial cells, their function as neural stem cells (NSCs) and progenitor cells. First we give an overview of glial stem and progenitor cells during development; these are the radial glial cells that act as NSCs and other glial progenitors, highlighting the distinction between the lineage of cells in vivo and their potential when exposed to a different environment, e.g., in vitro. We then proceed to the adult stage and discuss the glial cells that continue to act as NSCs across vertebrates and others that are more lineage-restricted, such as the adult NG2-glia, the most frequent progenitor type in the adult mammalian brain, that remain within the oligodendrocyte lineage. Upon certain injury conditions, a distinct subset of quiescent astrocytes reactivates proliferation and a larger potential, clearly demonstrating the concept of heterogeneity with distinct subtypes of, e.g., astrocytes or NG2-glia performing rather different roles after brain injury. These new insights not only highlight the importance of glial cells for brain repair but also their great potential in various aspects of regeneration.


2015 ◽  
Vol 39 (6) ◽  
pp. 750-758 ◽  
Author(s):  
Hui Ding ◽  
Guo-Hua Jin ◽  
Lin-Qing Zou ◽  
Xiao-Qing Zhang ◽  
Hao-Ming Li ◽  
...  

2016 ◽  
Vol 180 ◽  
pp. 78-83 ◽  
Author(s):  
Lei Xing ◽  
Juan Manuel Gutierrez-Villagomez ◽  
Dillon F. Da Fonte ◽  
Maddie J. Venables ◽  
Vance L. Trudeau

2018 ◽  
Vol 9 ◽  
Author(s):  
Dillon F. Da Fonte ◽  
Chris J. Martyniuk ◽  
Lei Xing ◽  
Vance L. Trudeau

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 3237
Author(s):  
Ana Cristina Ojalvo-Sanz ◽  
Laura López-Mascaraque

During embryonic development, progenitor cells are progressively restricted in their potential to generate different neural cells. A specific progenitor cell type, the radial glial cells, divides symmetrically and then asymmetrically to produce neurons, astrocytes, oligodendrocytes, and NG2-glia in the cerebral cortex. However, the potential of individual progenitors to form glial lineages remains poorly understood. To further investigate the cell progeny of single pallial GFAP-expressing progenitors, we used the in vivo genetic lineage-tracing method, the UbC-(GFAP-PB)-StarTrack. After targeting those progenitors in embryonic mice brains, we tracked their adult glial progeny in lower cortical layers. Clonal analyses revealed the presence of clones containing sibling cells of either a glial cell type (uniform clones) or two different glial cell types (mixed clones). Further, the clonal size and rostro-caudal cell dispersion of sibling cells differed depending on the cell type. We concluded that pallial E14 neural progenitors are a heterogeneous cell population with respect to which glial cell type they produce, as well as the clonal size of their cell progeny.


2020 ◽  
Vol 6 (45) ◽  
pp. eabd2068
Author(s):  
Zhen Li ◽  
William A. Tyler ◽  
Ella Zeldich ◽  
Gabriel Santpere Baró ◽  
Mayumi Okamoto ◽  
...  

How the rich variety of neurons in the nervous system arises from neural stem cells is not well understood. Using single-cell RNA-sequencing and in vivo confirmation, we uncover previously unrecognized neural stem and progenitor cell diversity within the fetal mouse and human neocortex, including multiple types of radial glia and intermediate progenitors. We also observed that transcriptional priming underlies the diversification of a subset of ventricular radial glial cells in both species; genetic fate mapping confirms that the primed radial glial cells generate specific types of basal progenitors and neurons. The different precursor lineages therefore diversify streams of cell production in the developing murine and human neocortex. These data show that transcriptional priming is likely a conserved mechanism of mammalian neural precursor lineage specialization.


2016 ◽  
Vol 144 ◽  
pp. 123-132 ◽  
Author(s):  
Lei Xing ◽  
Christopher J. Martyniuk ◽  
Crystal Esau ◽  
Dillon F. Da Fonte ◽  
Vance L. Trudeau

Development ◽  
1995 ◽  
Vol 121 (6) ◽  
pp. 1719-1730 ◽  
Author(s):  
L. Feng ◽  
N. Heintz

Formation and maintenance of a radial glial scaffold is fundamental for development of the vertebrate central nervous system. In mammals, radial glia arise in the neuroepithelium immediately prior to differentiation and migration of neurons away from the ventricular zones, and they are maintained until neuronal migration subsides. We have previously shown that expression of the brain lipid-binding protein (BLBP) in radial glia throughout the developing CNS is strictly correlated with the differentiation and migration of neurons upon these cells, and that BLBP function is required to maintain differentiation of primary cerebellar glial cells in vitro (Feng, L., Hatten, M. E. and Heintz, N. (1994). Neuron 12, 895–908). In this study, we demonstrate that BLBP transcription in vivo involves multiple regulatory elements, and that the dynamic temporal and spatial pattern of BLBP expression in radial and Bergmann glial cells throughout the developing CNS is programmed by a single radial glial cell-specific element (RGE). Furthermore, we demonstrate that BLBP expression in primary cerebellar glial cells requires coculture with differentiating neurons, and that this induction is regulated by the radial glia-specific element. The fact that transcription of BLBP in response to neurons in vitro and its dynamic regulation in radial glia throughout the CNS in vivo are both controlled by the RGE provides the first direct evidence supporting a role for differentiating neurons in the epigenetic regulation of radial glial cell function in vivo.


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