Early Formation of a GFAP-Positive Cell Population in the Ventricular Zone during Chicken Brain Development

2010 ◽  
Vol 191 (1) ◽  
pp. 57-65 ◽  
Author(s):  
Akvilė Norkutė ◽  
Markus Kipp ◽  
Jon Dang ◽  
Diedrich Graf von Keyserlingk ◽  
Angelija Valančiūtė ◽  
...  
2015 ◽  
Vol 37 (2) ◽  
pp. 131-141 ◽  
Author(s):  
Shuhong Qiao ◽  
Ramin Homayouni

Dab2IP (DOC-2/DAB2 interacting protein) is a GTPase-activating protein which is involved in various aspects of brain development in addition to its roles in tumor formation and apoptosis in other systems. In this study, we carefully examined the expression profile of Dab2IP and investigated its physiological role during brain development using a Dab2IP-knockdown (KD) mouse model created by retroviral insertion of a LacZ-encoding gene-trapping cassette. LacZ staining revealed that Dab2IP is expressed in the ventricular zone as well as the cortical plate and the intermediate zone. Immunohistochemical analysis showed that Dab2IP protein is localized in the leading process and proximal cytoplasmic regions of migrating neurons in the intermediate zone. Bromodeoxyuridine birth dating experiments in combination with immunohistochemical analysis using layer-specific markers showed that Dab2IP is important for proper positioning of a subset of layer II-IV neurons in the developing cortex. Notably, neuronal migration was not completely disrupted in the cerebral cortex of Dab2IP-KD mice and disruption of migration was not strictly layer specific. Previously, we found that Dab2IP regulates multipolar transition in cortical neurons. Others have shown that Rap1 regulates the transition from multipolar to bipolar morphology in migrating postmitotic neurons through N-cadherin signaling and somal translocation in the superficial layer of the cortical plate through integrin signaling. Therefore, we examined whether Rap1 and integrin signaling were affected in Dab2IP-KD brains. We found that Dab2IP-KD resulted in higher levels of activated Rap1 and integrin in the developing cortex. Taken together, our results suggest that Dab2IP plays an important role in the migration and positioning of a subpopulation of later-born (layers II-IV) neurons, likely through the regulation of Rap1 and integrin signaling.


2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Maximilian Middelkamp ◽  
Lisa Ruck ◽  
Christoph Krisp ◽  
Piotr Sumisławski ◽  
Behnam Mohammadi ◽  
...  

AbstractLIN28A overexpression has been identified in malignant brain tumors called embryonal tumors with multilayered rosettes (ETMR) but its specific role during brain development remains largely unknown. Radial glia cells of the ventricular zone (VZ) are proposed as a cell of origin for ETMR. We asked whether an overexpression of LIN28A in such cells might affect brain development or result in the formation of brain tumors.Constitutive overexpression of LIN28A in hGFAP-cre::lsl-Lin28A (GL) mice led to a transient increase of proliferation in the cortical VZ at embryonic stages but no postnatal brain tumor formation. Postnatally, GL mice displayed a pyramidal cell layer dispersion of the hippocampus and altered spine and dendrite morphology, including reduced dendritic spine densities in the hippocampus and cortex. GL mice displayed hyperkinetic activity and differential quantitative MS-based proteomics revealed altered time dependent molecular functions regarding mRNA processing and spine morphogenesis. Phosphoproteomic analyses indicated a downregulation of mTOR pathway modulated proteins such as Map1b being involved in microtubule dynamics.In conclusion, we show that Lin28A overexpression transiently increases proliferation of neural precursor cells but it is not sufficient to drive brain tumors in vivo. In contrast, Lin28A impacts on protein abundancy patterns related to spine morphogenesis and phosphorylation levels of proteins involved in microtubule dynamics, resulting in decreased spine densities of neurons in the hippocampus and cortex as well as in altered behavior. Our work provides new insights into the role of LIN28A for neuronal morphogenesis and development and may reveal future targets for treatment of ETMR patients.


2012 ◽  
Vol 349 (2) ◽  
pp. 289-297 ◽  
Author(s):  
Stijn L.J. Van Herck ◽  
Stijn Geysens ◽  
Joke Delbaere ◽  
Przemko Tylzanowski ◽  
Veerle M. Darras

Cell Reports ◽  
2018 ◽  
Vol 23 (3) ◽  
pp. 692-700 ◽  
Author(s):  
Ankita Thawani ◽  
Devika Sirohi ◽  
Richard J. Kuhn ◽  
Donna M. Fekete

Neuroscience ◽  
2012 ◽  
Vol 221 ◽  
pp. 69-85 ◽  
Author(s):  
S. Geysens ◽  
J.L. Ferran ◽  
S.L.J. Van Herck ◽  
P. Tylzanowski ◽  
L. Puelles ◽  
...  

2020 ◽  
Vol 26 (13) ◽  
pp. 1428-1437 ◽  
Author(s):  
Ignazio de Trizio ◽  
Mariella Errede ◽  
Antonio d'Amati ◽  
Francesco Girolamo ◽  
Daniela Virgintino

P-Glycoprotein (P-gp) is a 170-kDa transmembrane glycoprotein that works as an efflux pump and confers multidrug resistance (MDR) in normal tissues and tumors, including nervous tissues and brain tumors. In the developing telencephalon, the endothelial expression of P-gp, and the subcellular localization of the transporter at the luminal endothelial cell (EC) plasma membrane are early hallmarks of blood-brain barrier (BBB) differentiation and suggest a functional BBB activity that may complement the placental barrier function and the expression of P-gp at the blood-placental interface. In early fetal ages, P-gp has also been immunolocalized on radial glia cells (RGCs), located in the proliferative ventricular zone (VZ) of the dorsal telencephalon and now considered to be neural progenitor cells (NPCs). RG-like NPCs have been found in many regions of the developing brain and have been suggested to give rise to neural stem cells (NSCs) of adult subventricular (SVZ) neurogenic niches. The P-gp immunosignal, associated with RG-like NPCs during cortical histogenesis, progressively decreases in parallel with the last waves of neuroblast migrations, while ‘outer’ RGCs and the deriving astrocytes do not stain for the efflux transporter. These data suggest that in human glioblastoma (GBM), P-gp expressed by ECs may be a negligible component of tumor MDR. Instead, tumor perivascular astrocytes may dedifferentiate and resume a progenitor-like P-gp activity, becoming MDR cells and contribute, together with perivascular P-gpexpressing glioma stem-like cells (GSCs), to the MDR profile of GBM vessels. In conclusion, the analysis of Pgp immunolocalization during brain development may contribute to identify the multiple cellular sources in the GBM vessels that may be involved in P-gp-mediated chemoresistance and can be responsible for GBM therapy failure and tumor recurrence.


Author(s):  
Georgia Tsapara ◽  
Irwin Andermatt ◽  
Esther T. Stoeckli

2013 ◽  
Vol 190 ◽  
pp. 96-104 ◽  
Author(s):  
Stijn L.J. Van Herck ◽  
Stijn Geysens ◽  
Joke Delbaere ◽  
Veerle M. Darras

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