Loss of cep57 function induces G1 arrest and microcephaly

Centrosomal protein 57 (CEP57) is essential for centrosome organization, regulating nucleation and stabilization of microtubules, and mitotic spindle formation. Here, we uncover uncharacterized, distinct functions of cep57 in modulating cell cycle progression, spindle pole integrity and directing cranial neural crest specification during early embryonic development. We demonstrate that cep57 localizes to both the nucleus and centrosomes in zebrafish blastulae, and its depletion results in spindle pole focusing defects and G1 phase arrest. Additionally, the cep57 deficient embryos exhibit increased apoptosis, disrupted cranial neural crest specifiers, and microcephaly-associated characteristics. The comparative proteome analysis reveals a previously uncharacterized role of Cep57 in regulating G1 arrest and DNA damage-related proteins, including Dapk1, Arid3B, Cpped1, Pp2a, and Annexin V, as well as key cell cycle modulators such as Smc4, 14-3-3, Ctf8, and CDK7. Hence, this study highlights the broader, multifaceted role of cep57 in cell cycle progression and early neurodevelopment with fresh insights into its functional significance beyond centrosome regulation.