scholarly journals Decision letter: Extracellular matrix-inducing Sox9 promotes both basal progenitor proliferation and gliogenesis in developing neocortex

2019 ◽  
Author(s):  
Silvia Nicolis
2019 ◽  
Author(s):  
Ayse Güven ◽  
Denise Stenzel ◽  
Katherine R. Long ◽  
Marta Florio ◽  
Holger Brandl ◽  
...  

AbstractNeocortex expansion is largely based on the proliferative capacity of basal progenitors (BPs), which is increased by extracellular matrix (ECM) components via integrin signaling. Here we show that Sox9 drives expression of ECM components and that laminin 211 increases BP proliferation in embryonic mouse neocortex. Examination of Sox9 expression reveals that Sox9 is expressed in BPs of developing ferret and human, but not mouse neocortex. Functional studies by conditional Sox9 expression in the mouse BP lineage demonstrate increased BP proliferation, reduced Tbr2 and induction of Olig2 expression, indicative of premature gliogenesis. Conditional Sox9 expression also results in cell non-autonomous stimulation of BP proliferation followed by increased production of upper-layer neurons. Collectively, our findings demonstrate that Sox9 exerts concerted effects on transcription, BP proliferation, neuron production, and neurogenic as well as gliogenic BP cell fate, suggesting that Sox9 acts a master regulator in the subventricular zone to promote neocortical expansion.


eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Ayse Güven ◽  
Nereo Kalebic ◽  
Katherine R Long ◽  
Marta Florio ◽  
Samir Vaid ◽  
...  

Neocortex expansion is largely based on the proliferative capacity of basal progenitors (BPs), which is increased by extracellular matrix (ECM) components via integrin signaling. Here we show that the transcription factor Sox9 drives expression of ECM components and that laminin 211 increases BP proliferation in embryonic mouse neocortex. We show that Sox9 is expressed in human and ferret BPs and is required for BP proliferation in embryonic ferret neocortex. Conditional Sox9 expression in the mouse BP lineage, where it normally is not expressed, increases BP proliferation, reduces Tbr2 levels and induces Olig2 expression, indicative of premature gliogenesis. Conditional Sox9 expression also results in cell-non-autonomous stimulation of BP proliferation followed by increased upper-layer neuron production. Our findings demonstrate that Sox9 exerts concerted effects on transcription, BP proliferation, neuron production, and neurogenic vs. gliogenic BP cell fate, suggesting that Sox9 may have contributed to promote neocortical expansion.


Neuron ◽  
2020 ◽  
Vol 108 (6) ◽  
pp. 1113-1129.e6
Author(s):  
Lei Xing ◽  
Nereo Kalebic ◽  
Takashi Namba ◽  
Samir Vaid ◽  
Pauline Wimberger ◽  
...  

2018 ◽  
Author(s):  
Milos Kostic ◽  
Judith T.M.L. Paridaen ◽  
Katherine Long ◽  
Nereo Kalebic ◽  
Barbara Langen ◽  
...  

SummaryThe expansion of the neocortex during mammalian evolution has been linked to an enlargement of the subventricular zone during cortical development and an increase in the proliferation of the basal progenitors residing therein. Here, we explored a potential role of YAP, the major downstream effector of the Hippo signaling pathway, in proliferation of basal progenitors. We show that YAP expression and activity are high in ferret and human basal progenitors, which are known to exhibit high proliferative capacity, but low in mouse basal progenitors, which lack such capacity. To induce YAP activity in mouse basal progenitors, we expressed a constitutively active YAP (CA-YAP). This resulted in an increase in proliferation of basal progenitor. In addition, CA-YAP expressing mouse basal progenitors promoted the production of upper-layer neurons. To investigate if YAP is required for the proliferation of basal progenitors, we pharmacologically interfered with the function of YAP in the developing ferret and human neocortex. This resulted in a decrease of cycling basal progenitors. In concert, genetical interference with the function of YAP in ferret developing neocortex resulted in decreased abundance of basal progenitors. Together, our data indicate that YAP promotes the proliferation of basal progenitors and suggest that changes in YAP activity levels contributed to the evolutionary expansion of the neocortex.


Cell Reports ◽  
2019 ◽  
Vol 27 (4) ◽  
pp. 1103-1118.e6 ◽  
Author(s):  
Milos Kostic ◽  
Judith T.M.L. Paridaen ◽  
Katherine R. Long ◽  
Nereo Kalebic ◽  
Barbara Langen ◽  
...  

2020 ◽  
Author(s):  
Katrin Gerstmann ◽  
Karine Kindbeiter ◽  
Ludovic Telley ◽  
Muriel Bozon ◽  
Camille Charoy ◽  
...  

SummaryIn the embryonic brain, dynamic regulation of apical adhesion is fundamental to generate correct numbers and identity of precursors and neurons. Radial glial cells (RGC) in the cerebral cortex are tightly attached to adjacent neighbours. However, cells committed to differentiate reduce their adhesiveness to detach and settle at distal position from the apical border. Whether diffusible signals delivered from the cerebrospinal fluid (CSF) contribute to the regulation of apical adhesion dynamics remain fully unknown. Here we report that unconventional pre-formed complexes of class3-Semaphorins (Sema) and Neuropilins (Nrp) are released into the cerebrospinal fluid (CSF) from sources including the choroid plexus. Through analysis of mutant mouse models and various ex vivo assays, we propose that two different complexes, Sema3B/Nrp2 and Sema3F/Nrp1, bind to apical endfeet of RGCs, and exert dual regulation of their attachment, nuclei dynamics, that oppositely promotes or inhibits basal progenitor and neuron differentiation. This reveals unexpected contributions of CSF-delivered guidance molecules during cortical development.


Author(s):  
L. Terracio ◽  
A. Dewey ◽  
K. Rubin ◽  
T.K. Borg

The recognition and interaction of cells with the extracellular matrix (ECM) effects the normal physiology as well as the pathology of all multicellular organisms. These interactions have been shown to influence the growth, development, and maintenance of normal tissue function. In previous studies, we have shown that neonatal cardiac myocytes specifically interacts with a variety of ECM components including fibronectin, laminin, and collagens I, III and IV. Culturing neonatal myocytes on laminin and collagen IV induces an increased rate of both cell spreading and sarcomerogenesis.


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