Central Topography of Cranial Motor Nuclei Controlled by Differential Cadherin Expression

Marc Astick,Kristina Tubby,Waleed M Mubarak,Sarah Guthrie,Stephen R Price

doi:10.1016/j.cub.2014.08.067

Abstract

SummaryNeuronal nuclei are prominent, evolutionarily conserved features of vertebrate central nervous system (CNS) organization [1]. Nuclei are clusters of soma of functionally related neurons and are located in highly stereotyped positions. Establishment of this CNS topography is critical to neural circuit assembly. However, little is known of either the cellular or molecular mechanisms that drive nucleus formation during development, a process termed nucleogenesis [2, 3, 4, 5]. Brainstem motor neurons, which contribute axons to distinct cranial nerves and whose functions are essential to vertebrate survival, are organized exclusively as nuclei. Cranial motor nuclei are composed of two main classes, termed branchiomotor/visceromotor and somatomotor [6]. Each of these classes innervates evolutionarily distinct structures, for example, the branchial arches and eyes, respectively. Additionally, each class is generated by distinct progenitor cell populations and is defined by differential transcription factor expression [7, 8]; for example, Hb9 distinguishes somatomotor from branchiomotor neurons. We characterized the time course of cranial motornucleogenesis, finding that despite differences in cellular origin, segregation of branchiomotor and somatomotor nuclei occurs actively, passing through a phase of each being intermingled. We also found that differential expression of cadherin cell adhesion family members uniquely defines each motor nucleus. We show that cadherin expression is critical to nucleogenesis as its perturbation degrades nucleus topography predictably.

Highlights

Cranial motor neurons at these levels are born within these rhombomeres, and there is little rostrocaudal migration of the motor neurons while they take up their stereotyped positions
Differential Cadherin Expression Defines Cranial Motor Nuclei We focused our attention on the cadherin family of cell adhesion molecules as candidates to drive the sorting and segregation of cranial motor nuclei, as they play key roles in the organization of spinal lateral motor column neurons [15,16,17,18,19,20,21]
Cadherin-20 overexpression had no effect on cranial motor neuron progenitor domains and motor neuron number, similar to that found after ND390 expression (Supplemental Experimental Procedures and Figures S4A–S4C)

Summary

Introduction

At stage 26 (st26) [14], the migratory streams of both the presumptive facial and accessory abducens nuclei have converged and the neurons of each nucleus are intermingled (Figure 1B). The accessory abducens and facial motor nuclei at r5 were scattered over a larger area after ND390 expression compared to the control (see the yellow brackets in Figures 4B and 4C). This effect was not observed where motor neurons were nonelectroporated (Figures S3I and S3J), suggesting that cell-autonomous cadherin function is essential for nucleogenesis.

Results

Conclusion