Semaphorin3A regulates neuronal polarization by suppressing axon formation and promoting dendrite growth

Maya Shelly; Laura Cancedda; Byung Kook Lim; Andrei T. Popescu; Pei lin Cheng; Hongfeng Gao; Mu ming Poo

doi:10.1016/j.neuron.2011.06.041

Semaphorin3A regulates neuronal polarization by suppressing axon formation and promoting dendrite growth

Maya Shelly
, Laura Cancedda
, Byung Kook Lim
, Andrei T. Popescu
, Pei lin Cheng
, Hongfeng Gao
, Mu ming Poo

Neurobiology and Behavior

Italian Institute of Technology
University of California at Berkeley
Stanford University

Research output: Contribution to journal › Article › peer-review

185 Scopus citations

Abstract

Semaphorin 3A (Sema3A) is a secreted factor known to guide axon/dendrite growth and neuronal migration. We found that it also acts as a polarizing factor for axon/dendrite development in cultured hippocampal neurons. Exposure of the undifferentiated neurite to localized Sema3A suppressed its differentiation into axon and promoted dendrite formation, resulting in axon formation away from the Sema3A source, and bath application of Sema3A to polarized neurons promoted dendrite growth but suppressed axon growth. Fluorescence resonance energy transfer (FRET) imaging showed that Sema3A elevated the cGMP but reduced cAMP and protein kinase A (PKA) activity, and its axon suppression is attributed to the downregulation of PKA-dependent phosphorylation of axon determinants LKB1 and GSK-3β. Downregulating Sema3A signaling in rat embryonic cortical progenitors via in utero electroporation of siRNAs against the Sema3A receptor neuropilin-1 also resulted in polarization defects in vivo. Thus, Sema3A regulates the earliest step of neuronal morphogenesis by polarizing axon/dendrite formation.

Original language	English
Pages (from-to)	433-446
Number of pages	14
Journal	Neuron
Volume	71
Issue number	3
DOIs	https://doi.org/10.1016/j.neuron.2011.06.041
State	Published - Aug 11 2011

Access to Document

10.1016/j.neuron.2011.06.041

Cite this

@article{75b780d2197940cab5321520575578a3,

title = "Semaphorin3A regulates neuronal polarization by suppressing axon formation and promoting dendrite growth",

abstract = "Semaphorin 3A (Sema3A) is a secreted factor known to guide axon/dendrite growth and neuronal migration. We found that it also acts as a polarizing factor for axon/dendrite development in cultured hippocampal neurons. Exposure of the undifferentiated neurite to localized Sema3A suppressed its differentiation into axon and promoted dendrite formation, resulting in axon formation away from the Sema3A source, and bath application of Sema3A to polarized neurons promoted dendrite growth but suppressed axon growth. Fluorescence resonance energy transfer (FRET) imaging showed that Sema3A elevated the cGMP but reduced cAMP and protein kinase A (PKA) activity, and its axon suppression is attributed to the downregulation of PKA-dependent phosphorylation of axon determinants LKB1 and GSK-3β. Downregulating Sema3A signaling in rat embryonic cortical progenitors via in utero electroporation of siRNAs against the Sema3A receptor neuropilin-1 also resulted in polarization defects in vivo. Thus, Sema3A regulates the earliest step of neuronal morphogenesis by polarizing axon/dendrite formation.",

author = "Maya Shelly and Laura Cancedda and Lim, \{Byung Kook\} and Popescu, \{Andrei T.\} and Cheng, \{Pei lin\} and Hongfeng Gao and Poo, \{Mu ming\}",

year = "2011",

month = aug,

day = "11",

doi = "10.1016/j.neuron.2011.06.041",

language = "English",

volume = "71",

pages = "433--446",

journal = "Neuron",

issn = "0896-6273",

number = "3",

}

TY - JOUR

T1 - Semaphorin3A regulates neuronal polarization by suppressing axon formation and promoting dendrite growth

AU - Shelly, Maya

AU - Cancedda, Laura

AU - Lim, Byung Kook

AU - Popescu, Andrei T.

AU - Cheng, Pei lin

AU - Gao, Hongfeng

AU - Poo, Mu ming

PY - 2011/8/11

Y1 - 2011/8/11

N2 - Semaphorin 3A (Sema3A) is a secreted factor known to guide axon/dendrite growth and neuronal migration. We found that it also acts as a polarizing factor for axon/dendrite development in cultured hippocampal neurons. Exposure of the undifferentiated neurite to localized Sema3A suppressed its differentiation into axon and promoted dendrite formation, resulting in axon formation away from the Sema3A source, and bath application of Sema3A to polarized neurons promoted dendrite growth but suppressed axon growth. Fluorescence resonance energy transfer (FRET) imaging showed that Sema3A elevated the cGMP but reduced cAMP and protein kinase A (PKA) activity, and its axon suppression is attributed to the downregulation of PKA-dependent phosphorylation of axon determinants LKB1 and GSK-3β. Downregulating Sema3A signaling in rat embryonic cortical progenitors via in utero electroporation of siRNAs against the Sema3A receptor neuropilin-1 also resulted in polarization defects in vivo. Thus, Sema3A regulates the earliest step of neuronal morphogenesis by polarizing axon/dendrite formation.

AB - Semaphorin 3A (Sema3A) is a secreted factor known to guide axon/dendrite growth and neuronal migration. We found that it also acts as a polarizing factor for axon/dendrite development in cultured hippocampal neurons. Exposure of the undifferentiated neurite to localized Sema3A suppressed its differentiation into axon and promoted dendrite formation, resulting in axon formation away from the Sema3A source, and bath application of Sema3A to polarized neurons promoted dendrite growth but suppressed axon growth. Fluorescence resonance energy transfer (FRET) imaging showed that Sema3A elevated the cGMP but reduced cAMP and protein kinase A (PKA) activity, and its axon suppression is attributed to the downregulation of PKA-dependent phosphorylation of axon determinants LKB1 and GSK-3β. Downregulating Sema3A signaling in rat embryonic cortical progenitors via in utero electroporation of siRNAs against the Sema3A receptor neuropilin-1 also resulted in polarization defects in vivo. Thus, Sema3A regulates the earliest step of neuronal morphogenesis by polarizing axon/dendrite formation.

UR - https://www.scopus.com/pages/publications/79961200456

U2 - 10.1016/j.neuron.2011.06.041

DO - 10.1016/j.neuron.2011.06.041

M3 - Article

C2 - 21835341

AN - SCOPUS:79961200456

SN - 0896-6273

VL - 71

SP - 433

EP - 446

JO - Neuron

JF - Neuron

IS - 3

ER -

Semaphorin3A regulates neuronal polarization by suppressing axon formation and promoting dendrite growth

Abstract

Access to Document

Other files and links

Fingerprint

Cite this