The heparan sulfate-modifying enzyme glucuronyl C5-epimerase HSE-5 controls Caenorhabditis elegans Q neuroblast polarization during migration.
Directional cell migration is fundamental for neural development, and extracellular factors are pivotal for this process. Heparan sulfate proteoglycans (HSPGs) that carry long chains of differentially modified sugar residues contribute to extracellular matrix; however, the functions of HSPG in guiding cell migration remain elusive. Here, we used the Caenorhabditis elegans mutant pool from the Million Mutation Project and isolated a mutant allele of the heparan sulfate-modifying enzyme glucuronyl C5-epimerase HSE-5. Loss-of-function of this enzyme resulted in defective Q neuroblast migration. We showed that hse-5 controlled Q cell migration in a cell non-autonomous manner. By performing live cell imaging in hse-5 mutant animals, we found that hse-5 controlled initial polarization during Q neuroblast migration. Furthermore, our genetic epistasis analysis demonstrated that lon-2 might act downstream of hse-5. Finally, rescue of the hse-5 mutant phenotype by expression of human and mouse hse-5 homologs suggested a conserved function for this gene in neural development. Taken together, our results indicated that proper HSPG modification in the extracellular matrix by HSE-5 is essential for neuroblast polarity during migration.
['Wang|Xiangming|X|', 'Liu|Jianhong|J|', 'Zhu|Zhiwen|Z|', 'Ou|Guangshuo|G|']
D000818:Animals D017173:Caenorhabditis elegans D029742:Caenorhabditis elegans Proteins D002238:Carbohydrate Epimerases D002465:Cell Movement D016764:Cell Polarity D004843:Epistasis, Genetic D006801:Humans D051379:Mice D018613:Microscopy, Confocal D058953:Neural Stem Cells D019998:Racemases and Epimerases D013045:Species Specificity
Heparan sulfate-modifying enzyme Q neuroblast Polarization Migration