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Dive into the research topics where Pei-Lin Cheng is active.

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Featured researches published by Pei-Lin Cheng.


Nature | 2012

Clonally related visual cortical neurons show similar stimulus feature selectivity

Ye Li; Hui Lu; Pei-Lin Cheng; Shaoyu Ge; Hua-Tai Xu; Song-Hai Shi; Yang Dan

A fundamental feature of the mammalian neocortex is its columnar organization. In the visual cortex, functional columns consisting of neurons with similar orientation preferences have been characterized extensively, but how these columns are constructed during development remains unclear. The radial unit hypothesis posits that the ontogenetic columns formed by clonally related neurons migrating along the same radial glial fibre during corticogenesis provide the basis for functional columns in adult neocortex. However, a direct correspondence between the ontogenetic and functional columns has not been demonstrated. Here we show that, despite the lack of a discernible orientation map in mouse visual cortex, sister neurons in the same radial clone exhibit similar orientation preferences. Using a retroviral vector encoding green fluorescent protein to label radial clones of excitatory neurons, and in vivo two-photon calcium imaging to measure neuronal response properties, we found that sister neurons preferred similar orientations whereas nearby non-sister neurons showed no such relationship. Interestingly, disruption of gap junction coupling by viral expression of a dominant-negative mutant of Cx26 (also known as Gjb2) or by daily administration of a gap junction blocker, carbenoxolone, during the first postnatal week greatly diminished the functional similarity between sister neurons, suggesting that the maturation of ontogenetic into functional columns requires intercellular communication through gap junctions. Together with the recent finding of preferential excitatory connections among sister neurons, our results support the radial unit hypothesis and unify the ontogenetic and functional columns in the visual cortex.


Proceedings of the National Academy of Sciences of the United States of America | 2011

Self-amplifying autocrine actions of BDNF in axon development

Pei-Lin Cheng; Ai-Hong Song; Yu-Hui Wong; Sheng Wang; Xiang Zhang; Mu-ming Poo

A critical step in neuronal development is the formation of axon/dendrite polarity, a process involving symmetry breaking in the newborn neuron. Local self-amplifying processes could enhance and stabilize the initial asymmetry in the distribution of axon/dendrite determinants, but the identity of these processes remains elusive. We here report that BDNF, a secreted neurotrophin essential for the survival and differentiation of many neuronal populations, serves as a self-amplifying autocrine factor in promoting axon formation in embryonic hippocampal neurons by triggering two nested positive-feedback mechanisms. First, BDNF elevates cytoplasmic cAMP and protein kinase A activity, which triggers further secretion of BDNF and membrane insertion of its receptor TrkB. Second, BDNF/TrkB signaling activates PI3-kinase that promotes anterograde transport of TrkB in the putative axon, further enhancing local BDNF/TrkB signaling. Together, these self-amplifying BDNF actions ensure stable elevation of local cAMP/protein kinase A activity that is critical for axon differentiation and growth.


Neuron | 2011

Phosphorylation of E3 Ligase Smurf1 Switches Its Substrate Preference in Support of Axon Development

Pei-Lin Cheng; Hui Lu; Maya Shelly; Hongfeng Gao; Mu-ming Poo

Ubiquitin E3 ligases serve for ubiquitination of specific substrates, and its ligase efficacy is regulated by interacting proteins or substrate modifications. Whether and how the ligases themselves are modified by cellular signaling is unclear. Here we report that protein kinase A (PKA)-dependent phosphorylation of Smad Ubiquitin Regulatory Factor 1 (Smurf1) can switch its substrate preference between two proteins of opposing actions on axon development. Extracellular factors that promote axon formation elevated Smurf1 phosphorylation at a PKA site Thr³⁰⁶, and preventing this phosphorylation reduced axon formation in cultured hippocampal neurons and impaired polarization of cortical neurons in vivo. Thr³⁰⁶-phosphorylation changed the relative affinities of Smurf1 for its substrates, leading to reduced degradation of polarity protein Par6 and increased degradation of growth-inhibiting RhoA. Thus, PKA-dependent phosphorylation of the E3 ligase could switch its substrate preference, contributing to selective protein degradation required for localized cellular function.


Annual Review of Neuroscience | 2012

Early Events in Axon/Dendrite Polarization

Pei-Lin Cheng; Mu-ming Poo

Differentiation of axons and dendrites is a critical step in neuronal development. Here we review the evidence that axon/dendrite formation during neuronal polarization depends on the intrinsic cytoplasmic asymmetry inherited by the postmitotic neuron, the exposure of the neuron to extracellular chemical factors, and the action of anisotropic mechanical forces imposed by the environment. To better delineate the functions of early signals among a myriad of cellular components that were shown to influence axon/dendrite formation, we discuss their functions by distinguishing their roles as determinants, mediators, or modulators and consider selective degradation of these components as a potential mechanism for axon/dendrite polarization. Finally, we examine whether these early events of axon/dendrite formation involve local autocatalytic activation and long-range inhibition, as postulated by Alan Turing for the morphogenesis of patterned biological structure.


Developmental Cell | 2015

Stage-Dependent Axon Transport of Proteasomes Contributes to Axon Development.

Meng-Tsung Hsu; Chin-Lin Guo; Angela Y. Liou; Ting-Ya Chang; Ming-Chong Ng; Bogdan I. Florea; Herman S. Overkleeft; Yen-Lin Wu; Jung-Chi Liao; Pei-Lin Cheng

Axon extension at the growing tip requires elevated local protein supply, with a capability sustainable over long axons in varying environments. The exact mechanisms, however, remain elusive. Here we report that axon-promoting factors elicited a retrograde transport-dependent removal of proteasomes from nascent axon terminals, thereby increasing protein stability at axon tips. Such an effect occurred through phosphorylation of a dynein-interacting proteasome adaptor protein Ecm29. During the transition from immature neurites to nascent axons in cultured hippocampal neurons, live-cell imaging revealed a significant increase of the retrograde axonal transport of fluorescently labeled 20S proteasomes. This retrograde proteasome transport depended on neuron stage and increased with axon lengths. Blockade of retrograde transport caused accumulation of proteasomes, reduction of axon growth, and attenuation of growth-associated Par6 at the axon tip of newly polarized neurons. Our results delineate a regulatory mechanism that controls proteasome abundance via preferential transport required for axon development in newborn neurons.


Scientific Reports | 2017

Ascl1 promotes tangential migration and confines migratory routes by induction of Ephb2 in the telencephalon

Yuan Hsuan Liu; Jin-Wu Tsai; Jia Long Chen; Wan Shan Yang; Pei Ching Chang; Pei-Lin Cheng; David L. Turner; Yuchio Yanagawa; Tsu Wei Wang; Jenn Yah Yu

During development, cortical interneurons generated from the ventral telencephalon migrate tangentially into the dorsal telencephalon. Although Achaete-scute family bHLH transcription factor 1 (Ascl1) plays important roles in the developing telencephalon, whether Ascl1 regulates tangential migration remains unclear. Here, we found that Ascl1 promoted tangential migration along the ventricular zone/subventricular zone (VZ/SVZ) and intermediate zone (IZ) of the dorsal telencephalon. Distal-less homeobox 2 (Dlx2) acted downstream of Ascl1 in promoting tangential migration along the VZ/SVZ but not IZ. We further identified Eph receptor B2 (Ephb2) as a direct target of Ascl1. Knockdown of EphB2 disrupted the separation of the VZ/SVZ and IZ migratory routes. Ephrin-A5, a ligand of EphB2, was sufficient to repel both Ascl1-expressing cells in vitro and tangentially migrating cortical interneurons in vivo. Together, our results demonstrate that Ascl1 induces expression of Dlx2 and Ephb2 to maintain distinct tangential migratory routes in the dorsal telencephalon.


Scientific Reports | 2016

Type VI adenylyl cyclase negatively regulates GluN2B-mediated LTD and spatial reversal learning.

Ching-Pang Chang; Cheng-Ta Lee; Wen-Hsien Hou; Meng-Syuan Lin; Hsing-Lin Lai; Chen-Li Chien; Chen Chang; Pei-Lin Cheng; Cheng-Chang Lien; Yijuang Chern

The calcium-sensitive type VI adenylyl cyclase (AC6) is a membrane-bound adenylyl cyclase (AC) that converts ATP to cAMP under stimulation. It is a calcium-inhibited AC and integrates negative inputs from Ca2+ and multiple other signals to regulate the intracellular cAMP level. In the present study, we demonstrate that AC6 functions upstream of CREB and negatively controls neuronal plasticity in the hippocampus. Genetic removal of AC6 leads to cyclase-independent and N-terminus of AC6 (AC6N)-dependent elevation of CREB expression, and enhances the expression of GluN2B-containing NMDA receptors in hippocampal neurons. Consequently, GluN2B-dependent calcium signaling and excitatory postsynaptic current, long-term depression, and spatial reversal learning are enhanced in the hippocampus of AC6−/− mice without altering the gross anatomy of the brain. Together, our results suggest that AC6 negatively regulates neuronal plasticity by modulating the levels of CREB and GluN2B in the hippocampus.


Developmental Neurobiology | 2015

Second messenger signaling for neuronal polarization: Cell mechanics-dependent pattern formation

Chin-Lin Guo; Pei-Lin Cheng

Neuronal polarization is a critical step in the neuronal morphogenesis. Despite the identification of several evolutionarily conserved factors for neural polarization, the exact mechanisms by which cells initiate and maintain polarity remain to be characterized. Here, we review the recent progress on the roles of second messengers, specifically the cyclic nucleotides and membrane‐associated phospholipids, in the initiation, propagation, and integration of polarization signals, and propose an inhibitor‐free model for neural polarization. The characteristic features of neuron polarization include the formation of single axon and multiple dendrites. These features involve chemical and mechanical mechanisms such as reaction‐diffusion and tug‐of‐war, by which second messengers can act in concert to initiate and stabilize the cellular asymmetry. Nevertheless, biochemical factors eliciting the long‐range inhibition remain ambiguous. Thus, we provide a simple, inhibitor‐free model that can incorporate known cytochemical and cytomechanical factors, and produce features of neuronal polarization in environments provided with minimized extracellular regulators.


Mechanisms of Development | 2017

PS4.40Ascl1 promotes tangential migration and confines migratory routes by induction of Ephb2 in the telencephalon

Yuan-Hsuan Liu; Jin-Wu Tsai; Jia-Long Chen; Wan-Shan Yang; Pei Ching Chang; Pei-Lin Cheng; David L. Turner; Tsu Wei Wang; Jenn-Yah Yu

Adult neurogenesis persists throughout life in the mammalian subventricular zone (SVZ)-olfactory bulb (OB) pathway and the hippocampal dentate gyrus (DG). Although the precise mechanism regulating adult neurogenesis remains unclear, accumulating evidence implicates that adult neurogenesis plays important roles in neuropsychiatric disorders and maternal behaviors. Rab18, a Ras-like small GTPase, is recently identified to negatively regulate the secretory pathway. From ENU-mutagenized mouse screening, a null mutant line of Rab18 was identified and postpartum Rab18 null female mice had higher rates of neonaticide and infanticide, suggesting that these mice had defects in maternal behaviors and might suffer from postpartum anxiety/depression (PPD). Since adult neurogenesis is required for maternal behaviors and anti-anxiety, we hypothesize that Rab18 may regulate maternal behaviors through mediating adult neurogenesis. We found that adult neurogenesis in the OB and DG was decreased in both virgin and postpartum Rab18 null mice. Moreover, progenitor cell numbers and cell proliferation in neural stem cell niches of Rab18 null female mice were also decreased. In addition, prolactin was not induced in postpartum Rab18 null mice. Since dopamine is a prolactin inhibitor, we also found that the midbrain dopamine level in Rab18 null female mice was increased. Finally, prolactin could rescue neurogenic defects in postpartum Rab18 null mice. This study suggests that Rab18 regulates adult neurogenesis through dopamine and prolactin.


Experimental Neurology | 2015

Relay of cyclin-dependent kinases in the regulation of axonal growth

Ting-Ya Chang; Pei-Lin Cheng

One of the most perplexing problems in neuronal morphogenesis is how local polarity signals echo genetic instructions to establish structural and functional asymmetry of neuronal compartments, i.e., axons, dendrites, and synapses. However studying these phenomena is complicated because both genes and the local environment influence the phenotype of developing neurons. Cell cycle-associated nuclear transcription regulators involved in axon extension, for example Cdk12 and Cdk13, thus provide ideal models for connecting spatially separated events at specific developmental time points.

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Mu-ming Poo

Chinese Academy of Sciences

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Jin-Wu Tsai

National Yang-Ming University

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Pei Ching Chang

National Yang-Ming University

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Tsu Wei Wang

National Taiwan Normal University

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Byung Kook Lim

University of California

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Chin-Lin Guo

California Institute of Technology

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David L. Turner

Molecular and Behavioral Neuroscience Institute

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Maya Shelly

Stony Brook University

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