Hs6st1, also known as heparan sulfate 6-O-sulfotransferase 1, is an enzyme crucial for heparan sulfate (HS) modification. HS is an extracellular component essential for regulating morphogen gradients by modulating morphogen binding. Hs6st1 is involved in multiple biological processes and signaling pathways, such as those related to neuroectodermal patterning, and is associated with diseases like delayed puberty and Kallmann syndrome [1,2,3]. Genetic models, like KO mouse models, are valuable for studying its functions.

In Xenopus, Hs6st1 knockout using the Nuclease technology system expands the neural plate region, followed by retinal malformation, indicating its role in neuroectodermal patterning by selectively regulating morphogen distribution. In mice, Hs6st1 knockout leads to severe corpus callosum phenotypes, with a hyperactivation of Erk signaling in the embryonic telencephalon, and this phenotype can be rescued by suppressing Fgf8/Erk axis components. Also, in mice, heterozygous Hs6st1 loss causes self-limited delayed puberty [1,4,2].

In conclusion, Hs6st1 is vital for regulating morphogen distribution in processes like neuroectodermal patterning and for proper development of the corpus callosum. Its insufficiency is linked to self-limited delayed puberty. The study of Hs6st1 using KO mouse models has provided insights into its role in these biological processes and disease conditions, enhancing our understanding of related mechanisms.