title: AIP1-mediated actin disassembly is required for postnatal germ cell migration and spermatogonial stem cell niche establishment.
abstract: In mammals, spermatogonial stem cells (SSCs) arise from early germ cells called gonocytes, which are derived from primordial germ cells during embryogenesis and remain quiescent until birth. After birth, these germ cells migrate from the center of testicular cord, through Sertoli cells, and toward the basement membrane to form the SSC pool and establish the SSC niche architecture. However, molecular mechanisms underlying germ cell migration and niche establishment are largely unknown. Here, we show that the actin disassembly factor actin interacting protein 1 (AIP1) is required in both germ cells and Sertoli cells to regulate this process. Germ cell-specific or Sertoli cell-specific deletion of Aip1 gene each led to significant defects in germ cell migration after postnatal day 4 or 5, accompanied by elevated levels of actin filaments (F-actin) in the affected cells. Furthermore, our data demonstrated that interaction between germ cells and Sertoli cells, likely through E-cadherin-mediated cell adhesion, is critical for germ cells' migration toward the basement membrane. At last, Aip1 deletion in Sertoli cells decreased SSC self-renewal, increased spermatogonial differentiation, but did not affect the expression and secretion levels of growth factors, suggesting that the disruption of SSC function results from architectural changes in the postnatal niche.
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animals for Disease Study, Model Animal Research Center, Nanjing University, Nanjing, China.
authors.forename: J
authors.initials: J
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animals for Disease Study, Model Animal Research Center, Nanjing University, Nanjing, China.
authors.forename: P
authors.initials: P
authors.lastname: Wan
authors.affiliation: State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China.
authors.forename: M
authors.initials: M
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animals for Disease Study, Model Animal Research Center, Nanjing University, Nanjing, China.
authors.forename: J
authors.initials: J
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animals for Disease Study, Model Animal Research Center, Nanjing University, Nanjing, China.
authors.forename: X
authors.initials: X
authors.lastname: Gao
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animals for Disease Study, Model Animal Research Center, Nanjing University, Nanjing, China.
authors.forename: B
authors.initials: B
authors.lastname: Hu
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animals for Disease Study, Model Animal Research Center, Nanjing University, Nanjing, China.
authors.forename: J
authors.initials: J
authors.lastname: Han
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animals for Disease Study, Model Animal Research Center, Nanjing University, Nanjing, China.
authors.forename: L
authors.initials: L
authors.lastname: Chen
authors.affiliation: Bio-X Institute, Shanghai Jiaotong University, Shanghai, China.
authors.forename: K
authors.initials: K
authors.lastname: Sun
authors.affiliation: Bio-X Institute, Shanghai Jiaotong University, Shanghai, China.
authors.forename: J
authors.initials: J
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China.
authors.forename: X
authors.initials: X
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animals for Disease Study, Model Animal Research Center, Nanjing University, Nanjing, China.
authors.forename: X
authors.initials: X
authors.lastname: Huang
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animals for Disease Study, Model Animal Research Center, Nanjing University, Nanjing, China.
authors.forename: J
authors.initials: J
authors.lastname: Chen
mesh_terms: D000199:Actins / Q000235:genetics; D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D015820:Cadherins / Q000378:metabolism; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics*; D002448:Cell Adhesion / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D002465:Cell Movement / Q000235:genetics; D047108:Embryonic Development / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D005854:Germ Cells / Q000166:cytology / Q000254:growth & development*; D051528:Guanylate Kinases; D006801:Humans; D008297:Male; D018345:Mice, Knockout; D012708:Sertoli Cells / Q000166:cytology* / Q000378:metabolism; D013093:Spermatogonia / Q000166:cytology / Q000254:growth & development*; D055153:Stem Cell Niche / Q000235:genetics*; D013737:Testis / Q000254:growth & development / Q000378:metabolism
chemical_list: D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; D015820:Cadherins; D002352:Carrier Proteins; D051528:Guanylate Kinases; C485777:MAGI2 protein, human