Localization in Oogenesis of Maternal Regulators of Embryonic Development

Abstract

Cell polarity generates intracellular asymmetries and functional regionalization in tissues and morphogenetic processes. Cell polarity in development often relies on mechanisms of RNA localization to specific subcellular domains to define the identity of future developing tissues. The totipotent egg of most animals illustrates in a grand way the importance of cell polarity and RNA localization in regulating multiple crucial developmental events. The polarization of the egg arises during its development in oogenesis. RNAs localize asymmetrically in the early oocyte defining its animal-vegetal (AV) axis, which upon further elaboration in mid- and late-oogenesis stages produces a mature egg with specific localized factors along its AV axis. These localized factors will define the future anterior-posterior (AP) and dorsal-ventral (DV) axes of the embryo. Furthermore, AV polarity confines germ cell determinants to the vegetal pole, from where they redistribute to the cleavage furrows of the 2- and 4-cell stage embryo, ultimately specifying the primordial germ cells (PGCs). The sperm entry region during fertilization is also defined by the AV axis. In frogs and fish, sperm enters through the animal pole, similar to the mouse where it enters predominantly in the animal half. Thus, AV polarity establishment and RNA localization are involved in all the major events of early embryonic development. In this chapter, we will review the RNA localization mechanisms in vertebrate oocytes that are key to embryonic patterning, referring to some of the groundbreaking studies in frog oocytes and incorporating the current genetic evidence from the zebrafish.

Coordination of cellular differentiation, polarity, mitosis and meiosis – New findings from early vertebrate oogenesis

“…In all cases ultrastructural analysis shows that the Bb is located at the nuclear periphery and is composed of aggregated mitochondria and electron dense material, likely corresponding to RNA. The Bb has been most studied in Xenopus and zebrafish, where Bb localization of specific mRNAs, proteins, and mitochondria are directly demonstrated and its role in oocyte polarization is readily evident (reviewed in (Escobar-Aguirre et al, 2017)). While Bb formation has been poorly understood, new studies have begun to unravel the mechanisms of oocyte symmetry breaking that lead to its formation (Elkouby et al, 2016) as we discuss below.…”

“…Two pathways deliver mRNA-protein (mRNPs) granules to the oocyte vegetal pole during oogenesis: the Balbiani body pathway, which initially determines the vegetal pole, and the “late pathway”, which localizes mRNAs to the defined vegetal pole (Escobar-Aguirre et al, 2017). The Balbiani body (Bb) is an aggregate of mRNPs and mitochondria that initially forms adjacent to the nucleus, enlarges and resides in the cytoplasm, and then localizes to the oocyte cortex, where it dissociates (Bontems et al, 2009b; Elkouby et al, 2016; Gupta et al, 2010; Heim et al, 2014; Marlow & Mullins, 2008a; Riemer et al, 2015).…”

“…The AV axis functions in embryonic patterning and germ cell specification. Since this is the topic of a recent review (Escobar-Aguirre et al, 2017), we only briefly discuss it here. The oocyte and egg vegetal pole harbors factors that regulate dorsal-ventral axis formation via activation of a Wnt signaling pathway (Langdon & Mullins, 2011).…”

“…The Macf1 protein is a member of the spectraplakin family of cytoskeletal linker proteins that connect cytoskeletal elements in various physiological functions (Liem, 2016). Macf1 may thus link cytoplasmic microtubules or cytokeratins in the Bb to cortical actin in docking the Bb to the oocyte cortex and in disassembling it (Escobar-Aguirre et al, 2017; Gupta et al, 2010). …”

Methods for the analysis of early oogenesis in Zebrafish

“…Size: 100–300 µm diameter; stages: late st.I and st.II, Bb disassembly, vegetal pole RNA and protein localization via Bb and late pathway [28], animal pole RNA localization, and cortical granule formation.…”