⍺TAT1-dependent microtubule acetylation is required for touch sensation in zebrafish but not for cilia-driven morphogenesis

Acetylation of ⍺-tubulin at lysine 40 (⍺-tubK40Ac) is a conserved post-translational modification enriched on long-lived microtubules, yet its roles in vertebrate development remain incompletely defined. In zebrafish, morpholino-based knockdown of the ⍺-tubulin acetyltransferase ⍺TAT1 has been reported to cause severe developmental defects, in contrast to genetic studies in mammals. Here, we generated loss-of-function alleles of ⍺TAT1 in zebrafish and found that mutants, including maternal-zygotic mutants, are viable, fertile, and develop normally. ⍺TAT1 mutants lack detectable ⍺-tubK40Ac in all examined tissues, suggesting that ⍺TAT1 is solely responsible for this modification in zebrafish. Despite the complete loss of ⍺-tubK40Ac in both cilia and neurons, cilia structure and motility were preserved, and multiple cilia-dependent developmental processes, including axial morphogenesis, Reissner fiber formation, and left-right patterning, remained intact. In contrast, ⍺TAT1 mutants exhibited impaired touch-evoked escape responses, a phenotype that was rescued by wild-type but not catalytically inactive ⍺TAT1. Together, these findings establish ⍺TAT1 as the sole ⍺-tubulin K40 acetyltransferase in zebrafish and support a requirement for ⍺-tubK40Ac in normal somatosensory behavior, despite its dispensability for embryonic development and cilia-dependent morphogenesis.