Temporal identity transition from Purkinje cell progenitors to GABAergic interneuron progenitors in the cerebellum

Seto, Yusuke; Nakatani, Tomoya; Masuyama, Norihisa; Taya, Shinichiro; Kumai, Minoru; Minaki, Yasuko; Hamaguchi, Akiko; Inoue, Yukiko; Inoue, Tohru; Miyashita, Satoshi; Fujiyama, Tomoyuki; Yamada, Mayumi; Chapman, Heather; Campbell, Kenneth; Magnuson, Mark A.; Wright, Christopher V.E.; Kawaguchi, Yoshiya; Ikenaka, Kazuhiro; Takebayashi, Hirohide; Ishiwata, Shin’ichi; Ono, Yūichi; Hoshino, Mikio

doi:10.1038/ncomms4337

Cited by 96 publications

(122 citation statements)

References 49 publications

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“…Among Ptf1a + ventricular zone precursors, Olig1/2 + and Gsx1 + precursor cells are commited to develop into Rorα + Purkinje cells and Pax2 + interneurons, respectively. Olig1/2 and Gsx1 mutually represses each other during this temporal transition (Seto et al, 2014 cKO cerebella was the decreased proliferation of granule precursor cells of the EGL. Granule precursor cells contribute to the proper cerebellar growth and shape up the foliation pattern throughout embryonic and early postnatal stages (Martinez et al, 2013;Zervas et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

Polycomb Ezh2 controls the fate of GABAergic neurons in the embryonic cerebellum

et al. 2016

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Although the genetic interactions between signaling pathways and transcription factors have been largely decoded, much remains to be learned about the epigenetic regulation of cerebellar development. Here, we report that cerebellar deletion of Ezh2, the methyltransferase subunit of the PRC2 complex, results in reduced H3K27me3 and profound transcriptional dysregulation, including that of a set of transcription factors directly involved in cerebellar neuronal cell-type specification and differentiation. Such transcriptional changes lead to increased GABAergic interneurons and decreased Purkinje cells. Transcriptional changes also inhibit the proliferation of granule precursor cells derived from the rhombic lip. The loss of both cell types ultimately results in cerebellar hypoplasia. These findings indicate Ezh2/PRC2 plays crucial roles in regulating neurogenesis from both cerebellar germinal zones.

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Section: Discussionmentioning

confidence: 99%

Polycomb Ezh2 controls the fate of GABAergic neurons in the embryonic cerebellum

et al. 2016

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“…In the developing cerebellum, Purkinje cells are born in the ventricular zone of the fourth ventricle and migrate radially (Kapfhammer ; Roussel & Hatten ; Hoshino ; Seto et al . ), although a recent report has indicated that Purkinje cells that are generated at E10.5 in the posterior periventricular region of the lateral cerebellum migrate tangentially towards the anterior direction (Miyata et al . ) (Fig.…”

Section: Cdk5 In Brain Developmentmentioning

confidence: 99%

Cdk5 regulates multiple cellular events in neural development, function and disease

Kawauchi

2014

Dev Growth Differ

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Cyclin-dependent kinases (CDKs) generally regulate cell proliferation in dividing cells, including neural progenitors. In contrast, an unconventional CDK, Cdk5, is predominantly activated in post-mitotic cells, and involved in various cellular events, such as microtubule and actin cytoskeletal organization, cell-cell and cell-extracellular matrix adhesions, and membrane trafficking. Interestingly, recent studies have indicated that Cdk5 is associated with several cell cycle-related proteins, Cyclin-E and p27kip1 . Taking advantage of multiple functionality, Cdk5 plays important roles in neuronal migration, layer formation, axon elongation and dendrite arborization in many regions of the developing brain, including cerebral cortex and cerebellum. Cdk5 is also required for neurogenesis at least in the cerebral cortex. Furthermore, Cdk5 is reported to control neurotransmitter release at presynaptic sites, endocytosis of the NMDA receptor at postsynaptic sites and dendritic spine remodeling, and thereby regulate synaptic plasticity and memory formation and extinction. In addition to these physiological roles in brain development and function, Cdk5 is associated with many neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis. In this review, I will introduce the physiological and pathological roles of Cdk5 in mammalian brains from the viewpoint of not only in vivo phenotypes but also its molecular and cellular functions.

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“…Previous studies reveal co‐expression of a number of bHLH transcription factors within the Ptf1a expression territory of the VZ (Zordan, Croci, Hawkes, & Consalez, ), suggesting mosaics of bHLH multiple transcription factor programs drive GABAergic cell‐type specificity. More recently, the bHLH transcription factor gene Olig2 and the homeobox transcription factor gene Gsx1 have been identified as key temporal regulators of VZ progenitor cell fate (Seto et al, ). Using gain‐ and loss‐of‐function mutations in mice, Seto et al () showed the switch from a Purkinje cell (PC) to inhibitory interneuron cell fate from the VZ is negatively regulated by Olig2 expression in the dorsal region and positively regulated by Gsx1 expression in the ventral region.…”

Section: Introductionmentioning

confidence: 99%

“…More recently, the bHLH transcription factor gene Olig2 and the homeobox transcription factor gene Gsx1 have been identified as key temporal regulators of VZ progenitor cell fate (Seto et al, ). Using gain‐ and loss‐of‐function mutations in mice, Seto et al () showed the switch from a Purkinje cell (PC) to inhibitory interneuron cell fate from the VZ is negatively regulated by Olig2 expression in the dorsal region and positively regulated by Gsx1 expression in the ventral region. During development, PC progenitors transition to become inhibitory interneuron progenitors spreading from ventral to dorsal (Seto et al, ).…”

Section: Introductionmentioning

confidence: 99%

“…Using gain‐ and loss‐of‐function mutations in mice, Seto et al () showed the switch from a Purkinje cell (PC) to inhibitory interneuron cell fate from the VZ is negatively regulated by Olig2 expression in the dorsal region and positively regulated by Gsx1 expression in the ventral region. During development, PC progenitors transition to become inhibitory interneuron progenitors spreading from ventral to dorsal (Seto et al, ). However, the mechanism(s) by which each of the inhibitory interneuron cell‐types of the cerebellum are derived from Ptf1a ‐expressing progenitors remains unknown.…”

Section: Introductionmentioning

confidence: 99%

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Conditional deletion of Neurog1 in the cerebellum of postnatal mice delays inhibitory interneuron maturation

Obana

Zhou

Furmanski

et al. 2018

J of Neuroscience Research

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The transcriptional programs that drive the generation of diverse GABAergic neuron populations from their common progenitor pools in the developing cerebellum remain unclear. Neurog1 is a pro-neural basic helix-loop-helix transcription factor expressed in GABAergic progenitor cells in the ventricular zone (VZ) of embryos and subsequently in the presumptive white matter (pWM) tracts of developing postnatal mice. Genetic inducible fate-mapping labels Purkinje cells and all inhibitory interneuron cell types of the cerebellar cortex. As conventional Neurog1 knockout (KO) mice are neonatal lethal, we generated Neurog1 mutant mice to examine the effects of conditional Neurog1 deletion on the postnatal development of the cerebellum. Targeted Neurog1 loss-of-function in the developing cerebellum does not result in significant differences in cerebellar morphology or in the number of GABAergic neurons in the cerebellar cortex of mice at postnatal day 21 (P21). To determine the effects of Neurog1 deletion on GABAergic progenitors, we quantified rates of cell proliferation and cell cycle progression or re-entry in embryonic Neurog1 and postnatal Neurog1 mutants. The data revealed no significant effect of Neurog1 loss-of-function on embryonic day 12.5 (E12.5) VZ progenitors or on P5 and P6 progenitors in the pWM at P7. However, 4-5 day pulse-labeling of P5 and P6 progenitors revealed reductions in inhibitory interneuron dispersal from the pWM to the cerebellar cortex in P10 conditional Neurog1 KO mice. Thus, our conditional Neurog1 KO approach reveals a requirement for Neurog1 activity in inhibitory interneuron cell dispersal from pWM tracts in the developing cerebellum of postnatal mice.

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Temporal identity transition from Purkinje cell progenitors to GABAergic interneuron progenitors in the cerebellum

Cited by 96 publications

References 49 publications

Polycomb Ezh2 controls the fate of GABAergic neurons in the embryonic cerebellum

Polycomb Ezh2 controls the fate of GABAergic neurons in the embryonic cerebellum

Cdk5 regulates multiple cellular events in neural development, function and disease

Conditional deletion of Neurog1 in the cerebellum of postnatal mice delays inhibitory interneuron maturation

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