Basal protrusions mediate spatiotemporal patterns of spinal neuron differentiation

TY - JOUR

T1 - Basal protrusions mediate spatiotemporal patterns of spinal neuron differentiation

AU - Hadjivasiliou, Zena

AU - Moore, Rachel E.

AU - McIntosh, Rebecca

AU - Galea, Gabriel L.

AU - Clarke, Jonathan D. W.

AU - Alexandre, Paula

PY - 2019/6/17

Y1 - 2019/6/17

N2 - During early spinal cord development, neurons of particular subtypes differentiate with a sparse periodic pattern while later neurons differentiate in the intervening space to eventually produce continuous columns of similar neurons. The mechanisms that regulate this spatiotemporal pattern are unknown. In vivo imaging in zebrafish reveals differentiating spinal neurons transiently extend two long protrusions along the basal surface of the spinal cord prior to axon initiation. These protrusions express Delta protein consistent with the hypothesis they influence Notch signalling at a distance of several cell diameters. Experimental reduction of laminin expression leads to smaller protrusions and shorter distances between differentiating neurons. The experimental data and a theoretical model support the proposal that neuronal differentiation pattern is regulated by transient basal protrusions that deliver temporally controlled lateral inhibition mediated at a distance. This work uncovers a stereotyped protrusive activity of new-born neurons that organizes long distance spatiotemporal patterning of differentiation.

AB - During early spinal cord development, neurons of particular subtypes differentiate with a sparse periodic pattern while later neurons differentiate in the intervening space to eventually produce continuous columns of similar neurons. The mechanisms that regulate this spatiotemporal pattern are unknown. In vivo imaging in zebrafish reveals differentiating spinal neurons transiently extend two long protrusions along the basal surface of the spinal cord prior to axon initiation. These protrusions express Delta protein consistent with the hypothesis they influence Notch signalling at a distance of several cell diameters. Experimental reduction of laminin expression leads to smaller protrusions and shorter distances between differentiating neurons. The experimental data and a theoretical model support the proposal that neuronal differentiation pattern is regulated by transient basal protrusions that deliver temporally controlled lateral inhibition mediated at a distance. This work uncovers a stereotyped protrusive activity of new-born neurons that organizes long distance spatiotemporal patterning of differentiation.

KW - basal protrusions

KW - lateral inhibition

KW - live imaging

KW - neuronal differentiation

KW - spatiotemporal pattern

KW - spinal cord

KW - zebrafish

U2 - 10.1016/j.devcel.2019.05.035

DO - 10.1016/j.devcel.2019.05.035

M3 - Article

SN - 1534-5807

VL - 49

SP - 907-919.e10

JO - Developmental Cell

JF - Developmental Cell

IS - 6

ER -