Submitted:
26 July 2026
Posted:
28 July 2026
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Abstract
Germ cell formation is a fundamental process in sex determination, playing crucial roles in balancing oogonia and spermatogonia self-renewal and development. However, the regulatory genes fundamental to germ cell self-renewal and development remain to be elucidated. In this study, we constructed zebrafish lima1a knockout mutants. Lima1a is a homolog of human LIMA1, which is involved in cell motility, gene regulation, cellular metabolism, and the epithelial-to-mesenchymal transition (EMT). These knockout mutants were used in subsequent experiments to clarify the roles of lima1a in sexual differentiation and germ cell development. Compared with wild type (WT), lima1a-/- zebrafish had smaller body sizes and smaller gonads. Nonetheless, lima1a-/- zebrafish produced mature gametes and maintained a comparable sex ratio to their WT siblings. At a juvenile stage, lima1a-/- females showed delayed and prolonged germ cell development, and this adversely affected follicle quality, subsequently impacting embryo development in adults. Additionally, adult male lima1a-/- zebrafish exhibited defective spermatogenesis, and the ovary-to-testis transition in juveniles was delayed and prolonged. At 45 days post-fertilization (dpf), we observed that the expression levels of ovary-specific and testis-specific genes were significantly disrupted during the sexual development of lima1a-/- zebrafish, suggesting that lima1a expression is crucial for the development and function of gonadal cells in ovaries and testes. These changes in gene expression also impacted the development of germ cells in lima1a-/- zebrafish and caused delayed puberty onset. Furthermore, Vim, a marker for EMT, was upregulated in lima1a-/- zebrafish gonadal cells, suggesting that lima1a maintains gonad differentiation and germ cell development by regulating the EMT process of gonadal cells. Collectively, these results reveal that lima1a is required for maintaining normal sexual development and the ovary-to-testis transition in juvenile zebrafish. Moreover, lima1a is required for gonadal germ cell development and maturation, and for embryo development.
Keywords:
lima1a
; germ cell development
; ovary-to-testis transition
; EMT
; zebrafish
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