Somatostatin-Igf1rb signalling antagonism drives primordial germ cell migration

Somatostatin 1.2 ( sst1.2 ), an orthologue of mammalian SST1 , has been shown to regulate primordial germ cell (PGC) number and fecundity in zebrafish. Furthermore, sst1.2 deficiency is associated with disordered germ plasm assembly and upregulation of the insulin-like growth factor 1 receptor b ( igf1rb ). Here, we investigated the effect of sst1.2 deficiency on PGC migration and found that PGCs clustered and moved more rapidly towards the gonadal ridge than in wild-type individuals. Further, the sdf-1 and cxcr4b genes, which encode, respectively, the chemokine and its receptor that guide PGC migration, were upregulated in the sst1.2 -deficient fish, along with the cell-cell adhesion factor E-cadherin. Knocking down igf1rb , a somatostatin downstream factor, downregulated sdf-1 , cxcr4b and E-cadherin and slowed PGC migration. We conclude that sst1.2 regulates PGC migration by inhibiting igf1rb . • sst1.2 gene deficiency upregulates sdf-1 cxcr4b and E-cadherin expression • igf1rb knockdown reduces PGC migration speed, rescuing the sst1.2- deficient phenotype • igf1rb knockdown brings the levels of sdf-1 , cxcr4b mRNA and E-cadherin protein in the sst1.2 mutants to those in the wild type • The somatostatin-Igf1rb axis regulates PGC migratory movement