scholarly journals ATF5 deficiency causes abnormal cortical development

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mariko Umemura ◽  
Yasuyuki Kaneko ◽  
Ryoko Tanabe ◽  
Yuji Takahashi
Keyword(s):  
Cerebral Cortex ◽  
Glial Cells ◽  
Leucine Zipper ◽  
Ventricular Zone ◽  
Cortical Development ◽  
Physiological Role ◽  
Basic Leucine Zipper ◽  
Radial Glial Cells ◽  
Radial Migration ◽  
Radial Glial

AbstractActivating transcription factor 5 (ATF5) is a member of the cAMP response element binding protein (CREB)/ATF family of basic leucine zipper transcription factors. We previously reported that ATF5-deficient (ATF5−/−) mice exhibited behavioural abnormalities, including abnormal social interactions, reduced behavioural flexibility, increased anxiety-like behaviours, and hyperactivity in novel environments. ATF5−/− mice may therefore be a useful animal model for psychiatric disorders. ATF5 is highly expressed in the ventricular zone and subventricular zone during cortical development, but its physiological role in higher-order brain structures remains unknown. To investigate the cause of abnormal behaviours exhibited by ATF5−/− mice, we analysed the embryonic cerebral cortex of ATF5−/− mice. The ATF5−/− embryonic cerebral cortex was slightly thinner and had reduced numbers of radial glial cells and neural progenitor cells, compared to a wild-type cerebral cortex. ATF5 deficiency also affected the basal processes of radial glial cells, which serve as a scaffold for radial migration during cortical development. Further, the radial migration of cortical upper layer neurons was impaired in ATF5−/− mice. These results suggest that ATF5 deficiency affects cortical development and radial migration, which may partly contribute to the observed abnormal behaviours.

scholarly journals A transient role of the ciliary gene Inpp5e in controlling direct versus indirect neurogenesis in cortical development

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Kerstin Hasenpusch-Theil ◽  
Christine Laclef ◽  
Matt Colligan ◽  
Eamon Fitzgerald ◽  
Katherine Howe ◽  
...  
Keyword(s):  
Cerebral Cortex ◽  
Glial Cells ◽  
Primary Cilia ◽  
Cortical Development ◽  
Newborn Mice ◽  
Radial Glial Cells ◽  
Radial Glial ◽  
Neuronal Subtype ◽  
Layer V

During the development of the cerebral cortex, neurons are generated directly from radial glial cells or indirectly via basal progenitors. The balance between these division modes determines the number and types of neurons formed in the cortex thereby affecting cortical functioning. Here, we investigate the role of primary cilia in controlling the decision between forming neurons directly or indirectly. We show that a mutation in the ciliary gene Inpp5e leads to a transient increase in direct neurogenesis and subsequently to an overproduction of layer V neurons in newborn mice. Loss of Inpp5e also affects ciliary structure coinciding with reduced Gli3 repressor levels. Genetically restoring Gli3 repressor rescues the decreased indirect neurogenesis in Inpp5e mutants. Overall, our analyses reveal how primary cilia determine neuronal subtype composition of the cortex by controlling direct versus indirect neurogenesis. These findings have implications for understanding cortical malformations in ciliopathies with INPP5E mutations.

scholarly journals ANO1/TMEM16A regulates process maturation in radial glial cells in the developing brain

2019 ◽  
Vol 116 (25) ◽  
pp. 12494-12499 ◽  
Author(s):  
Gyu-Sang Hong ◽  
Sung Hoon Lee ◽  
Byeongjun Lee ◽  
Jae Hyouk Choi ◽  
Soo-Jin Oh ◽  
...  
Keyword(s):  
Glial Cells ◽  
Ventricular Zone ◽  
Trophic Factors ◽  
Early Developmental Stage ◽  
Anoctamin 1 ◽  
Radial Glial Cells ◽  
Radial Glial ◽  
Early Developmental ◽  
The Brain ◽  
Deficient Mice

Neural stem cells (NSCs) are primary progenitor cells in the early developmental stage in the brain that initiate a diverse lineage of differentiated neurons and glia. Radial glial cells (RGCs), a type of neural stem cell in the ventricular zone, are essential for nurturing and delivering new immature neurons to the appropriate cortical target layers. Here we report that Anoctamin 1 (ANO1)/TMEM16A, a Ca2+-activated chloride channel, mediates the Ca2+-dependent process extension of RGCs. ANO1 is highly expressed and functionally active in RGCs of the mouse embryonic ventricular zone. Knockdown of ANO1 suppresses RGC process extension and protrusions, whereas ANO1 overexpression stimulates process extension. Among various trophic factors, brain-derived neurotrophic factor (BDNF) activates ANO1, which is required for BDNF-induced process extension in RGCs. More importantly, Ano1-deficient mice exhibited disrupted cortical layers and reduced cortical thickness. We thus conclude that the regulation of RGC process extension by ANO1 contributes to the normal formation of mouse embryonic brain.

scholarly journals Memo1-Mediated Tiling of Radial Glial Cells Facilitates Cerebral Cortical Development

Neuron ◽  
2019 ◽  
Vol 103 (5) ◽  
pp. 836-852.e5 ◽  
Author(s):  
Naoki Nakagawa ◽  
Charlotte Plestant ◽  
Keiko Yabuno-Nakagawa ◽  
Jingjun Li ◽  
Janice Lee ◽  
...  
Keyword(s):  
Glial Cells ◽  
Cortical Development ◽  
Radial Glial Cells ◽  
Radial Glial

scholarly journals Coevolution of radial glial cells and the cerebral cortex

Glia ◽  
2015 ◽  
Vol 63 (8) ◽  
pp. 1303-1319 ◽  
Author(s):  
Camino De Juan Romero ◽  
Víctor Borrell
Keyword(s):  
Cerebral Cortex ◽  
Glial Cells ◽  
Radial Glial Cells ◽  
Radial Glial

Role of GGF/neuregulin signaling in interactions between migrating neurons and radial glia in the developing cerebral cortex

Development ◽  
1997 ◽  
Vol 124 (18) ◽  
pp. 3501-3510 ◽  
Author(s):  
E.S. Anton ◽  
M.A. Marchionni ◽  
K.F. Lee ◽  
P. Rakic
Keyword(s):  
Cerebral Cortex ◽  
Glial Cells ◽  
Neuronal Migration ◽  
Lipid Binding ◽  
Soluble Form ◽  
Dependent Manner ◽  
Radial Glial Cells ◽  
Glial Development ◽  
Radial Glial

During neuronal migration to the developing cerebral cortex, neurons regulate radial glial cell function and radial glial cells, in turn, support neuronal cell migration and differentiation. To study how migrating neurons and radial glial cells influence each others' function in the developing cerebral cortex, we examined the role of glial growth factor (a soluble form of neuregulin), in neuron-radial glial interactions. Here, we show that GGF is expressed by migrating cortical neurons and promotes their migration along radial glial fibers. Concurrently, GGF also promotes the maintenance and elongation of radial glial cells, which are essential for guiding neuronal migration to the cortex. In the absence of GGF signaling via erbB2 receptors, radial glial development is abnormal. Furthermore, GGF's regulation of radial glial development is mediated in part by brain lipid-binding protein (BLBP), a neuronally induced, radial glial molecule, previously shown to be essential for the establishment and maintenance of radial glial fiber system. The ability of GGF to influence both neuronal migration and radial glial development in a mutually dependent manner suggests that it functions as a mediator of interactions between migrating neurons and radial glial cells in the developing cerebral cortex.

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