Motor Neurons with Axial Muscle Projections Specified by Wnt4/5 Signaling

Dritan Agalliu; Shinji Takada; Ilir Agalliu; Andrew P. McMahon; Thomas M. Jessell

doi:10.1016/j.neuron.2008.12.026

Motor Neurons with Axial Muscle Projections Specified by Wnt4/5 Signaling

Dritan Agalliu, Shinji Takada, Ilir Agalliu, Andrew P. McMahon, Thomas M. Jessell

Epidemiology & Population Health

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

80 Scopus citations

Abstract

Axial muscles are innervated by motor neurons of the median motor column (MMC). In contrast to the segmentally restricted motor columns that innervate limb, body wall, and neuronal targets, MMC neurons are generated along the entire length of the spinal cord. We show that the specification of MMC fate involves a dorsoventral signaling program mediated by three Wnt proteins (Wnt4, Wnt5a, and Wnt5b) expressed in and around the floor plate. These Wnts appear to establish a ventral^high to dorsal^low signaling gradient and promote MMC identity and connectivity by maintaining expression of the LIM homeodomain proteins Lhx3/4 in spinal motor neurons. Elevation of Wnt4/5 activity generates additional MMC neurons at the expense of other motor neuron columnar subtypes, whereas depletion of Wnt4/5 activity inhibits the production of MMC neurons. Thus, two dorsoventral signaling pathways, mediated by Shh and Wnt4/5, are required to establish an early binary divergence in motor neuron columnar identity.

Original language	English (US)
Pages (from-to)	708-720
Number of pages	13
Journal	Neuron
Volume	61
Issue number	5
DOIs	https://doi.org/10.1016/j.neuron.2008.12.026
State	Published - Mar 12 2009

Keywords

DEVBIO
MOLNEURO

ASJC Scopus subject areas

General Neuroscience

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10.1016/j.neuron.2008.12.026

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@article{053f2c7104d54171a02311b1d937ff6f,

title = "Motor Neurons with Axial Muscle Projections Specified by Wnt4/5 Signaling",

abstract = "Axial muscles are innervated by motor neurons of the median motor column (MMC). In contrast to the segmentally restricted motor columns that innervate limb, body wall, and neuronal targets, MMC neurons are generated along the entire length of the spinal cord. We show that the specification of MMC fate involves a dorsoventral signaling program mediated by three Wnt proteins (Wnt4, Wnt5a, and Wnt5b) expressed in and around the floor plate. These Wnts appear to establish a ventralhigh to dorsallow signaling gradient and promote MMC identity and connectivity by maintaining expression of the LIM homeodomain proteins Lhx3/4 in spinal motor neurons. Elevation of Wnt4/5 activity generates additional MMC neurons at the expense of other motor neuron columnar subtypes, whereas depletion of Wnt4/5 activity inhibits the production of MMC neurons. Thus, two dorsoventral signaling pathways, mediated by Shh and Wnt4/5, are required to establish an early binary divergence in motor neuron columnar identity.",

keywords = "DEVBIO, MOLNEURO",

author = "Dritan Agalliu and Shinji Takada and Ilir Agalliu and McMahon, {Andrew P.} and Jessell, {Thomas M.}",

note = "Funding Information: We thank Monica Mendelsohn and Jennifer Kirkland for assistance in mouse husbandry; Kathy MacArthur and Ira Schieren for help with the text and figures; Jan Kitajewski, Jeremy Nathans, Cliff Tabin, Roel Nusse, and Uta Franke for reagents and advice; Terry Yamaguchi for loop tail embryos; James Briscoe and Jeremy Dasen for critical comments on the manuscript; and Johan Ericson for discussions. T.M.J. was supported by grants from NINDS, Project ALS, The Leila and Harold Mathers Foundation, The Wellcome Trust. T.M.J. is an Investigator of the Howard Hughes Medical Institute. Work in A.P.M.'s laboratory was supported by a grant from the NIH (R37NS033642). ",

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AU - McMahon, Andrew P.

AU - Jessell, Thomas M.

N1 - Funding Information: We thank Monica Mendelsohn and Jennifer Kirkland for assistance in mouse husbandry; Kathy MacArthur and Ira Schieren for help with the text and figures; Jan Kitajewski, Jeremy Nathans, Cliff Tabin, Roel Nusse, and Uta Franke for reagents and advice; Terry Yamaguchi for loop tail embryos; James Briscoe and Jeremy Dasen for critical comments on the manuscript; and Johan Ericson for discussions. T.M.J. was supported by grants from NINDS, Project ALS, The Leila and Harold Mathers Foundation, The Wellcome Trust. T.M.J. is an Investigator of the Howard Hughes Medical Institute. Work in A.P.M.'s laboratory was supported by a grant from the NIH (R37NS033642).

PY - 2009/3/12

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N2 - Axial muscles are innervated by motor neurons of the median motor column (MMC). In contrast to the segmentally restricted motor columns that innervate limb, body wall, and neuronal targets, MMC neurons are generated along the entire length of the spinal cord. We show that the specification of MMC fate involves a dorsoventral signaling program mediated by three Wnt proteins (Wnt4, Wnt5a, and Wnt5b) expressed in and around the floor plate. These Wnts appear to establish a ventralhigh to dorsallow signaling gradient and promote MMC identity and connectivity by maintaining expression of the LIM homeodomain proteins Lhx3/4 in spinal motor neurons. Elevation of Wnt4/5 activity generates additional MMC neurons at the expense of other motor neuron columnar subtypes, whereas depletion of Wnt4/5 activity inhibits the production of MMC neurons. Thus, two dorsoventral signaling pathways, mediated by Shh and Wnt4/5, are required to establish an early binary divergence in motor neuron columnar identity.

AB - Axial muscles are innervated by motor neurons of the median motor column (MMC). In contrast to the segmentally restricted motor columns that innervate limb, body wall, and neuronal targets, MMC neurons are generated along the entire length of the spinal cord. We show that the specification of MMC fate involves a dorsoventral signaling program mediated by three Wnt proteins (Wnt4, Wnt5a, and Wnt5b) expressed in and around the floor plate. These Wnts appear to establish a ventralhigh to dorsallow signaling gradient and promote MMC identity and connectivity by maintaining expression of the LIM homeodomain proteins Lhx3/4 in spinal motor neurons. Elevation of Wnt4/5 activity generates additional MMC neurons at the expense of other motor neuron columnar subtypes, whereas depletion of Wnt4/5 activity inhibits the production of MMC neurons. Thus, two dorsoventral signaling pathways, mediated by Shh and Wnt4/5, are required to establish an early binary divergence in motor neuron columnar identity.

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Motor Neurons with Axial Muscle Projections Specified by Wnt4/5 Signaling

Abstract

Keywords

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