Altering the levels of nuclear import factors in early Xenopus laevis embryos affects later development

Abstract

More than just a container for DNA, the nuclear envelope carries out a wide variety of critical and highly regulated cellular functions. One of these functions is nuclear import, and in this study we investigate how altering the levels of nuclear transport factors impacts developmental progression and organismal size. During early Xenopus laevis embryogenesis, the timing of a key developmental event, the midblastula transition (MBT), is sensitive to nuclear import factor levels. How might altering nuclear import factors and MBT timing in the early embryo affect downstream development of the organism? We microinjected X . laevis two-cell embryos with mRNA to increase levels of importin α or NTF2, resulting in differential amounts of nuclear import factors in the two halves of the embryo. Compared to controls, these embryos exhibited delayed gastrulation, curved neural plates, and bent tadpoles with different sized eyes. Furthermore, embryos microinjected with NTF2 developed into smaller froglets compared to control microinjected embryos. We propose that altering nuclear import factors and nuclear size affects MBT timing, cell size, and cell number, subsequently disrupting later development. Thus, altering nuclear import factors early in development can affect function and size at the organismal level.

Quantitative Studies for Cell-Division Cycle Control

“…Conventionally, the nuclear-cytoplasmic ratio or karyoplasmic ratio has been considered to be a measure of cellular spatial information (Wilson, 1925; Jorgensen and Tyers, 2004). Previous researches proposed that the nuclear-cytoplasmic ratio dictates cell size-dependent CDC control in budding yeast and MBT triggering in Xenopus embryos (Newport and Kirschner, 1982a; Futcher, 1996) and altered size ratio can affect cell and organismal growth and development, and is associated with disease states (Edens et al, 2013; Jevtić and Levy, 2015; Jevtić et al, 2019). However, quantitative analyses of the allometric size scaling between cell and nucleus have been limited to studies using C. elegans and Xenopus embryos in animal cells (Arata et al, 2014; Jevtić and Levy, 2015).…”

Importin-11 is Essential for Normal Embryonic Development in Mice

“…In contrast, Ipo11 in human was expressed in the senescent diploid fibroblasts [24]. Moreover, the Jevtic et al [13] demonstrated that altering the levels of nuclear import factors in early Xenopus laevis embryos affects later development.…”

“…Besides this, overexpression of importin-11 can promote bladder cancer (BCa) progression, invasion and migration [12]. Importantly, it has been also reported that altering the levels of nuclear import factors importin α in early Xenopus laevis embryos affects later development [13].…”

A Novel Mutation in Cse1l Disrupts Brain and Eye Development with Specific Effects on Pax6 Expression

“…Because of CSE1L’s integral function in nuclear transport, it plays an important role in mediating a variety of cellular programs and signal transduction pathways. CSE1L functions as the exporter of importin-α; it has been shown in Xenopus laevis that disruption in levels of importin-α can have striking consequences in the developing embryo [ 38 ]. CSE1L interacts with various members of the Ras/Raf/MEK/ERK pathway, the PI3K pathway, and the cAMP pathway, serving as a hub for various signal transduction pathways [ 11 , 39 , 40 ].…”