Decreased Proliferation in the Neurogenic Niche, Disorganized Neuroblast Migration, and Increased Oligodendrogenesis in Adult Netrin-5-Deficient Mice

Ikegaya, Shunsuke; Iga, Yurika; Mikawa, Sumiko; Zhou, Li; Abe, Manabu; Sakimura, Kenji; Sato, Kohji; Yamagishi, Satoru

doi:10.3389/fnins.2020.570974

Cited by 5 publications

(3 citation statements)

References 49 publications

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“…Biochemical screens revealed that DSCAM is another receptor for netrin-5 ( Visser et al, 2015 ); however, the function of this interaction is not known, as in vitro growth cone collapse and turning assays have not been performed. Recently, we reported that netrin-5 is involved in organizing the rostral migratory stream in the adult mouse brain ( Ikegaya et al, 2020 ). However, the contribution of netrin-5 to cortical development remains to be determined.…”

Section: Roles Of Netrin Family Proteins In the Migration Of Corticalmentioning

confidence: 99%

Involvement of Netrins and Their Receptors in Neuronal Migration in the Cerebral Cortex

Yamagishi

Bandô

Sato

2021

Front. Cell Dev. Biol.

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In mammals, excitatory cortical neurons develop from the proliferative epithelium and progenitor cells in the ventricular zone and subventricular zone, and migrate radially to the cortical plate, whereas inhibitory GABAergic interneurons are born in the ganglionic eminence and migrate tangentially. The migration of newly born cortical neurons is tightly regulated by both extracellular and intracellular signaling to ensure proper positioning and projections. Non-cell-autonomous extracellular molecules, such as growth factors, axon guidance molecules, extracellular matrix, and other ligands, play a role in cortical migration, either by acting as attractants or repellents. In this article, we review the guidance molecules that act as cell–cell recognition molecules for the regulation of neuronal migration, with a focus on netrin family proteins, their receptors, and related molecules, including neogenin, repulsive guidance molecules (RGMs), Down syndrome cell adhesion molecule (DSCAM), fibronectin leucine-rich repeat transmembrane proteins (FLRTs), and draxin. Netrin proteins induce attractive and repulsive signals depending on their receptors. For example, binding of netrin-1 to deleted in colorectal cancer (DCC), possibly together with Unc5, repels migrating GABAergic neurons from the ventricular zone of the ganglionic eminence, whereas binding to α3β1 integrin promotes cortical interneuron migration. Human genetic disorders associated with these and related guidance molecules, such as congenital mirror movements, schizophrenia, and bipolar disorder, are also discussed.

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Section: Roles Of Netrin Family Proteins In the Migration Of Corticalmentioning

confidence: 99%

Involvement of Netrins and Their Receptors in Neuronal Migration in the Cerebral Cortex

Yamagishi

Bandô

Sato

2021

Front. Cell Dev. Biol.

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“…The permissive milieu of the SGZ allows NSC proliferation while promoting the specification and differentiation of DG neurons [71]. In the SGZ, newly generated neurons migrate to the granule cell layer, where they mature and develop dendritic branches [72]. These newly generated neurons integrate into the existing local DG network, where they acquire many of the long-range connections typical of mature granule cells and synapse locally upon inhibitory interneurons and mossy cells [73].…”

Section: Adult Neurogenesis In the Sgz Of The Hippocampus: Mechanism And Possible Functional Implicationsmentioning

confidence: 99%

Adult Neurogenesis: A Story Ranging from Controversial New Neurogenic Areas and Human Adult Neurogenesis to Molecular Regulation

Leal-Galicia

Chávez-Hernández

Mata

et al. 2021

IJMS

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The generation of new neurons in the adult brain is a currently accepted phenomenon. Over the past few decades, the subventricular zone and the hippocampal dentate gyrus have been described as the two main neurogenic niches. Neurogenic niches generate new neurons through an asymmetric division process involving several developmental steps. This process occurs throughout life in several species, including humans. These new neurons possess unique properties that contribute to the local circuitry. Despite several efforts, no other neurogenic zones have been observed in many years; the lack of observation is probably due to technical issues. However, in recent years, more brain niches have been described, once again breaking the current paradigms. Currently, a debate in the scientific community about new neurogenic areas of the brain, namely, human adult neurogenesis, is ongoing. Thus, several open questions regarding new neurogenic niches, as well as this phenomenon in adult humans, their functional relevance, and their mechanisms, remain to be answered. In this review, we discuss the literature and provide a compressive overview of the known neurogenic zones, traditional zones, and newly described zones. Additionally, we will review the regulatory roles of some molecular mechanisms, such as miRNAs, neurotrophic factors, and neurotrophins. We also join the debate on human adult neurogenesis, and we will identify similarities and differences in the literature and summarize the knowledge regarding these interesting topics.

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“…Immunostaining of tissue sections was performed as described previously (Ikegaya et al, 2020) with some modifications.…”

Section: Immunostainingmentioning

confidence: 99%

Expression of FLRT2 in Postnatal Central Nervous System Development and After Spinal Cord Injury

Shinoda

Ogawa

et al. 2021

Front. Mol. Neurosci.

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Fibronectin and leucine-rich transmembrane (FLRT) proteins are necessary for various developmental processes and in pathological conditions. FLRT2 acts as a homophilic cell adhesion molecule, a heterophilic repulsive ligand of Unc5/Netrin receptors, and a synaptogenic molecule; the last feature is mediated by binding to latrophilins. Although the function of FLRT2 in regulating cortical migration at the late gestation stage has been analyzed, little is known about the expression pattern of FLRT2 during postnatal central nervous system (CNS) development. In this study, we used Flrt2-LacZ knock-in (KI) mice to analyze FLRT2 expression during CNS development. At the early postnatal stage, FLRT2 expression was largely restricted to several regions of the striatum and deep layers of the cerebral cortex. In adulthood, FLRT2 expression was more prominent in the cerebral cortex, hippocampus, piriform cortex (PIR), nucleus of the lateral olfactory tract (NLOT), and ventral medial nucleus (VM) of the thalamus, but lower in the striatum. Notably, in the hippocampus, FLRT2 expression was confined to the CA1 region and partly localized on pre- and postsynapses whereas only few expression was observed in CA3 and dentate gyrus (DG). Finally, we observed temporally limited FLRT2 upregulation in reactive astrocytes around lesion sites 7 days after thoracic spinal cord injury. These dynamic changes in FLRT2 expression may enable multiple FLRT2 functions, including cell adhesion, repulsion, and synapse formation in different regions during CNS development and after spinal cord injury.

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Decreased Proliferation in the Neurogenic Niche, Disorganized Neuroblast Migration, and Increased Oligodendrogenesis in Adult Netrin-5-Deficient Mice

Cited by 5 publications

References 49 publications

Involvement of Netrins and Their Receptors in Neuronal Migration in the Cerebral Cortex

Involvement of Netrins and Their Receptors in Neuronal Migration in the Cerebral Cortex

Adult Neurogenesis: A Story Ranging from Controversial New Neurogenic Areas and Human Adult Neurogenesis to Molecular Regulation

Expression of FLRT2 in Postnatal Central Nervous System Development and After Spinal Cord Injury

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