Научная статья на тему 'Establishing neuronal identity in the cerebral cortex'

Establishing neuronal identity in the cerebral cortex Текст научной статьи по специальности «Биологические науки»

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Opera Medica et Physiologica
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Текст научной работы на тему «Establishing neuronal identity in the cerebral cortex»


The cerebral cortex contains layers of neurons sequentially generated by distinct lineage-related progenitors. At the onset of corticogenesis, the first-born progenitors are apical progenitors (APs), whose asymmetric division give birth directly to neurons. Later, they switch to indirect neurogenesis by generating intermediate progenitors (IPs), which give rise to projection neurons of all cortical layers. While a direct lineage relationship between APs and IPs has been established, the molecular mechanism that controls their transition remains elusive. Here we show that interfering with codon translation speed triggers endoplasmic reticulum stress and the unfolded protein response (UPR), further impairing the generation of IPs and leading to microcephaly. Moreover, we demonstrate that a progressive downregulation of UPR in cortical progenitors acts as physiological signal to amplify IPs and promotes indirect neurogenesis. Thus, our findings reveal a hitherto unrecognized contribution of UPR to cell fate acquisition during mammalian brain development.


1. Developmental Cell (2015) Laguesse et al.

Establishing Neuronal Identity in the Cerebral Cortex

C. Hanashima*

Riken center for developmental biology, kobe, Japan. * Presenting e-mail: hanashima@cdb.riken.jp

The functional integrity of the brain system relies on the precisely coordinated production of diverse neurons and their placement along the three-dimensional axis. Specifically in the cerebral cortex, progenitor cells produce distinct neuronal subtypes in a stereotypical order and establish a six-layer structure, which are further modified into functional areas. A prevailing view concerning the neurogenesis of the neocortex is that, neural stem cells undergo successive rounds of asymmetric cell divisions to produce the principal layer subtypes: preplate, deep-layer, and upper-layer neurons, through a progressive restriction in cell competence. Consistent with this view, we previously showed that foxg1, a forkhead transcription factor expressed in the telencephalon, plays a central role in establishing early gene network and switching neurogenesis from preplate cells to deep-layer neurons. However, our recent studies have also indicated that the specification and integration of neocortical neurons may rely on communication between distinct cell types, in addition to intrinsic transcriptional regulation. Here, i would like to present our findings on the mechanisms by which ne-ocortical subtype identities establish in the neocortex, by manipulating gene expression and number of neurogenesis in the developing mouse cortex. Our results indicate that neocortical progenitors integrate both intrinsic and extrinsic cues to generate distinct layer neurons, a system which ultimately balances the production of neocortical subtypes during development and possibly evolution.


1. T. Kumamoto, et al. Cell rep., 2013, 3(3), 931-945.

2. K. Toma, et al. J. Neurosci., 2014, 34(39):13259-76.

3. K. Toma, et al. Front. Neurosci., 2015, 9:274.

Laminar Cell Fate in the Neocortex: Can We Change it?

Victor Tarabykin*

Lobachevsky University, Nizhny Novgorod, Russia. * Presenting e-mail: victor.tarabykin@charite.de

Neocortical projection neurons are generated by two types of progenitors. While early progenitors give rise to deep layer neurons, late progenitors are restricted to produce upper layer neurons. Molecular mechanism that controls different potential of early versus late progenitors is not known. Here, we report that the high expression level of TrkC-T1; a non-catalytic splice variant of the neurotrophin receptor-TrkC, distinguishes early from late neocortical progenitors that express low TrkC-T1 level. We also provide direct evidence that the high level of TrkC-T1 promotes deep layers

Opera Med Physiol 2016 Vol. 2 (S1) 23


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