January 1, 2018;
Asymmetric development of the nervous system.
The human nervous system consists of seemingly symmetric left
halves. However, closer observation of the brain
reveals anatomical and functional lateralization. Defects in brain
asymmetry correlate with several neurological disorders, yet our understanding of the mechanisms used to establish lateralization in the human central nervous system is extremely limited. Here, we review left
asymmetries within the nervous system of humans and several model organisms, including rodents, Zebrafish, chickens, Xenopus, Drosophila, and the nematode Caenorhabditis elegans. Comparing and contrasting mechanisms used to develop left
asymmetry in the nervous system can provide insight into how the human brain
is lateralized. Developmental Dynamics 247:124-137, 2018. © 2017 Wiley Periodicals, Inc.
[+] show captions
References [+] :
Figure 1. Laterality in the human nervous system. The left and right hemispheres of the human brain are connected by the corpus callosum. The hemispheres display functional differences and control contralateral sides of the human body. Broca's and Wernicke's areas are language centers located in the left hemisphere of the majority of individuals. A, anterior; L, left; P, posterior; R, right.
Figure 2. Lateralization of the nervous system in Zebrafish and chicken. A: Asymmetry of the epithalamus and lateralization of eye use in Zebrafish. Nodal from the lateral plate mesoderm induces its own expression in the left habenula. FGF and Nodal act together to ensure directional asymmetry of the epithalamus. B: Lateralization of eye use in chicken. A, anterior; Hb, habenula; L, left; LHb, lateral habenula (green); LPM, lateral plate mesoderm; MHb, medial habenula (blue); P, posterior; Po, pineal organ (purple); Pp, parapineal organ (purple); R, right.
Establishment and maintenance of stochastic AWC asymmetry in C. elegans
(A) Top: Intercellular calcium signaling through NSY-5 gap junctions coordinates the AWCON/AWCOFF decision. Calcium signaling in non-AWC cells of the NSY-5 gap junction network promotes or inhibits the AWCON subtype. Bottom: In the default AWCOFF cell (right), calcium influx through voltage-gated calcium channels activates CaMKII to trigger a MAPK cascade and the expression of AWCOFF genes. In the induced AWCON cell (left), NSY-5 gap junctions, SLO BK potassium channels, and NSY-4 claudins suppress calcium channel-mediated signaling to promote the expression of AWCON genes. AWCON/AWCOFF orientation here is displayed as left/right, but can also occur in the opposite orientation. Red, active AWCON-promoting molecules; green, active AWCOFF-promoting molecules; grey, less active or inactive molecules. (B) Maintenance of AWC asymmetry. Red, active AWCON-maintaining molecules; green, active AWCOFF-maintaining molecules; grey, less active or inactive molecules. (Inset) A diagram of a worm head that demonstrates anatomical position of AWC and ASE neuron pairs. Anterior is to the top.
Figure 4. Establishment of directional ASE asymmetry in C. elegans. Priming and boosting of lsy-6 miRNA throughout the ASEL cell lineage leads to the ASEL identity. At the 4-cell stage, activated Notch receptor in the ASER precursor inhibits priming and boosting events of lsy-6 miRNA, leading to the ASER identity. TF, transcription factor; purple, active ASER-promoting molecules; blue, active ASEL-promoting molecules; grey, less active or inactive molecules; circles represent cells.
The habenula is crucial for experience-dependent modification of fear responses in zebrafish.