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Neuronal specification in the spinal cord: inductive signals and transcriptional codes

Abstract

Neural circuits are assembled with remarkable precision during embryonic development, and the selectivity inherent in their formation helps to define the behavioural repertoire of the mature organism. In the vertebrate central nervous system, this developmental program begins with the differentiation of distinct classes of neurons from progenitor cells located at defined positions within the neural tube. The mechanisms that specify the identity of neural cells have been examined in many regions of the nervous system and reveal a high degree of conservation in the specification of cell fate by key signalling molecules.

Key Points

  • Cell fate in the spinal cord is determined by rostrocaudal and dorsoventral patterning signals

  • Inductive signals from the notochord and the floor plate are important for patterning the ventral spinal cord

  • A gradient of Sonic hedgehog (Shh) signalling generates distinct cell fates in the ventral spinal cord

  • The Shh gradient is interpreted by a set of interacting homeodomain proteins

  • Combinatorial actions of the homeodomain proteins specify motor neuron differentiation

  • Bone morphogenetic proteins are also involved in the establishment of the Shh activity gradient

  • Extrinsic signals from the paraxial mesoderm and the lateral plate mesoderm enhance specification of motor neuron identity

  • LIM homeodomain protein expression is a marker of motor neuron subtype identity

  • The time at which neuronal progenitors exit the cell cycle and differentiate also influences cell fate

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Figure 1: Four stages of spinal cord development.
Figure 2: Shh expression by notochord and floor plate controls ventral pattern.
Figure 3: Three phases of Shh-mediated ventral neural patterning.
Figure 4: A molecular pathway for motor neuron generation.
Figure 5: A hierarchy of motor neuron identities.
Figure 6: Spatial organization of motor neurons in the developing spinal cord.
Figure 7: LIM homeodomain proteins control motor axon trajectory.
Figure 8: Retinoid signalling by early born LMC neurons and the control of lateral LMC neuronal identity.

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Acknowledgements

This article is for Julia Willis. I am grateful to many lab members, past and present, for their essential contributions to the ideas and work summarized here. S. Arber, J. Briscoe, A. Kania, S. Sockanathan and C. William made many helpful comments on the text and Kathy MacArthur and Ira Schieren provided expert help in its preparation. Work in the lab is supported by grants from the NIH, The Mathers Foundation, Project ALS and by the Howard Hughes Medical Institute. T.M.J. is an investigator of the Howard Hughes Medical Institute.

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DATABASE LINKS

RALDH-2

Shh

Nkx6.1

Nkx2.2

Irx3

gli1

gli2

gli3

COUP-TFII

Ptc

Smo

noggin

BMP4

Hhip

Notch

vitronectin

Isl1

Lhx3

Lhx4

Lim1

Lmx1b

Er81

ENCYLOPEDIA OF LIFE SCIENCES

Motor neurons and spinal control of movement

Glossary

PROPRIOCEPTION

The part of the somatosensory system that relays information about trunk and limb position.

ROSTROCAUDAL

The axis of the vertebrate embryo that runs from head to tail. Also referred to as the anterior–posterior axis at early stages of neural development.

DORSOVENTRAL

The axis of the vertebrate embryo that runs from back to stomach.

PARAXIAL MESODERM

Mesodermal cells that derive from the segmental plate mesoderm that flanks the midline axial mesoderm.

PRIMITIVE STREAK

A group of cells in gastrula-stage chick and mouse embryos that actively ingress from the epiblast layer to form mesodermal cell types.

NEURAL PLATE

The initial group of columnar neuroepithelial cells that forms as a result of neural induction.

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Jessell, T. Neuronal specification in the spinal cord: inductive signals and transcriptional codes. Nat Rev Genet 1, 20–29 (2000). https://doi.org/10.1038/35049541

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