MAB-5/Hox regulates the Q neuroblast transcriptome, includingcwn-1/Wnt,to mediate posterior migration inCaenorhabditis elegans

Abstract

AbstractNeurogenesis involves the precisely-coordinated action of genetic programs controlling large-scale neuronal fate specification down to terminal events of neuronal differentiation. The Q neuroblasts inC. elegans, QL on the left and QR on the right, divide, differentiate, and migrate in a similar pattern to produce three neurons each. However, QL on the left migrates posteriorly, and QR on the right migrates anteriorly. The MAB-5/Hox transcription factor is necessary and sufficient for posterior Q lineage migration, and is normally expressed only in the QL lineage. To define genes controlled by MAB-5 in the Q cells, fluorescence-activated cell sorting was utilized to isolate populations of Q cells at a time in early L1 larvae when MAB-5 first becomes active. Sorted Q cells fromwild-type, mab-5loss-of-function (lof), andmab-5gain-of-function (gof) mutants were subject to RNA-seq and differential expression analysis. Genes enriched in Q cells included those involved in cell division, DNA replication, and DNA repair, consist with the neuroblast stem cell identity of the Q cells at this stage. Genes affected bymab-5included those involved in neurogenesis, neural development, and interaction with the extracellular matrix.cwn-1,which encodes a Wnt signaling molecule, showed a paired response tomab-5in the Q cells:cwn-1expression was reduced inmab-5(lof)and increased inmab-5(gof), suggesting that MAB-5 is required forcwn-1expression in Q cells. MAB-5 is required to prevent anterior migration of the Q lineage while it transcriptionally reprograms the Q lineage for posterior migration. Functional genetic analysis revealed that CWN-1 is required downstream of MAB-5 to inhibit anterior migration of the QL lineage, likely in parallel to EGL-20/Wnt in a non-canonical Wnt pathway. In sum, work here describes a Q cell transcriptome, and a set of genes regulated by MAB-5 in the QL lineage. One of these genes,cwn-1,acts downstream ofmab-5in QL migration, indicating that this gene set includes other genes utilized by MAB-5 to facilitate posterior neuroblast migration.