Data from: HIPK4 is essential for murine spermiogenesis

Mammalian spermiogenesis is a remarkable cellular transformation, during which round spermatids elongate into chromatin-condensed spermatozoa. The signaling pathways that coordinate this process are poorly understood, and here we demonstrate that homeodomain-interacting protein kinase 4 (HIPK4) is required for sperm head shaping and male fertility in mice. HIPK4 is expressed in round and early elongating spermatids. Hipk4 knockout males are sterile, exhibiting phenotypes consistent with oligoasthenoteratozoospermia. Mutant sperm have reduced oocyte binding and are incompetent for in vitro fertilization, but can produce viable offspring via intracytoplasmic sperm injection. Ultrastructural analyses of HIPK4-null male germ cells reveal defects in the filamentous actin (F-actin)-scaffolded acroplaxome during spermatid elongation and abnormal head morphologies in mature spermatozoa. We further observe that HIPK4 overexpression induces branched F-actin structures in cultured fibroblasts, supporting a role for this kinase in cytoskeleton remodeling. Our findings establish HIPK4 as an essential regulator of spermiogenesis and potential target for male contraception.