RNA-binding protein TIAR is essential for primordial germ cell development

Abstract

Primordial germ cells (PGCs) give rise to both eggs and sperm via complex maturational processes that require both cell migration and proliferation. However, little is known about the genes controlling gamete formation during the early stages of PGC development. Although several mutations are known to severely reduce the number of PGCs reaching and populating the genital ridges, the molecular identity of only two of these genes is known: the c-kit receptor protein tyrosine kinase and the c-kit ligand (the steel factor). Herein, we report that mutant mice lacking TIAR, an RNA recognition motif͞ribonucleoprotein-type RNA-binding protein highly expressed in PGCs, fail to develop spermatogonia or oogonia. This developmental defect is a consequence of reduced survival of PGCs that migrate to the genital ridge around embryonic day 11.5 (E11.5). The numbers of PGCs populating the genital ridge in TIAR-deficient embryos are severely reduced compared to wild-type embryos by E11.5 and in the mutants PGCs are completely absent at E13.5. Furthermore, TIAR-deficient embryonic stem cells do not proliferate in the absence of exogenous leukemia inhibitory factor in an in vitro methylcellulose culture assay, supporting a role for TIAR in regulating cell proliferation. Because the development of PGCs relies on the action of several growth factors, these results are consistent with a role for TIAR in the expression of a survival factor or survival factor receptor that is essential for PGC development. TIAR-deficient mice thus provide a model system to study molecular mechanisms of PGC development and possibly the basis for some forms of idiopathic infertility.

TIA-1 or TIAR Is Required for DT40 Cell Viability

“…We conclude that DT40 cells require either TIA-1 or TIAR for viability. This suggests that the embryonic lethality observed following disruption of tia-1 or tiar genes in mice (7,26) is due to reduced cell viability, rather than problems with some specific process required for proper development.…”

“…On the other hand, ϳ50% of tia-1(Ϫ/Ϫ) mice die between embryonic day 16.5 and 3 weeks of age, though surviving mice appear normal (7). Mice with disrupted tiar genes show high levels of embryonic lethality, from 90 to 100% depending on the strain analyzed (7,26). Mice with both tia-1 and tiar genes disrupted die before embryonic day 7 (7).…”

Alternative pre-mRNA splicing regulation in cancer: pathways and programs unhinged

“…The two proteins function in similar processes and often exhibit partial redundancy (e.g., in Fas splicing, as mentioned above). However, they are not fully redundant, as knockout of either results in embryonic lethality (Beck et al 1998;Piecyk et al 2000). In addition, TIAR appears to have a unique role in germ cell development (Beck et al 1998).…”

“…However, they are not fully redundant, as knockout of either results in embryonic lethality (Beck et al 1998;Piecyk et al 2000). In addition, TIAR appears to have a unique role in germ cell development (Beck et al 1998). Among the earliest functions attributed to TIA-1 and TIAR was the ability to bind mRNAs and recruit them to cytoplasmic bodies (known as stress granules) in response to cellular stress such as heat shock (Kedersha et al 1999).…”

Understanding Ovarian Life Cycle

“…Bir RNA tan›ma motifi/ribonükleoprotein Primordial germ hücresi oluflumu (103) tip RNA ba¤lay›c› protein Pog Bilinmiyor Primordial germ hücresi proliferasyonu (104) …”