Roles for Maternal Replication Complex and DNA Repair Components
Several examples of zygotic mutants in which components of the replication and repair machinery are disrupted have been identified, including flat head/pol delta1, mcm5, and topoisomerase 2A in^zebrafish (Ryu et al., 2005; Plaster et al., 2006; Dovey et al., 2009), and topoisomerase I and topoisomerase 2A in the mouse (Morham et al., 1996; Akimitsu et al., 2003). The ability of the embryo to survive to developmental stages well beyond embryonic genome activation has been attributed to compensation by stable maternally loaded transcripts or protein; however, the maternal mutant phenotypes have not been reported.
Maternal Contributions to Segmentation and Somite Development
The somites are reiterated segments that form from mesoderm tissue during development, and will give rise to the axial skeleton and skeletal muscles in vertebrates. In zebrafish somite boundary formation begins with formation of primary epithelial boundaries via accumulation of extracellular matrix in the intersegmental regions (Henry et al., 2005). The misty somites mutant was identified through transposon mediated gene trap in zebrafish (Kotani and Kawakami, 2008). The insertion disrupts a conserved vertebrate-specific protein without obvious functional domains (Kotani and Kawakami, 2008). The misty somites gene trap allele does not completely eliminate Misty somites activity, and homozygous mutants for the insertion are viable to adulthood (Kotani and Kawakami, 2008). Maternal misty somites function regulates epithelialization during somite boundary formation and later maintains somite boundaries to allow normal muscle development through an unknown pathway and mechanism.
ALDH2: Maternal Roles for Retinoic Acid in Endoderm Development
Retinoic acid is a derivative of vitamin A, retinol. Retinol dehydrogenases convert retinol to retinaldehyde, which is then oxidized by Retinaldehyde dehydrogenases, Raldh or Aldh, to produce Retinoic acid. Aldh2 is the main, but not the only retinaldehyde dehydrogenase expressed in the early embryos of vertebrates. Several mutant alleles disrupting Aldh2, neckless, have been identified in zebrafish. These mutants reveal essential roles for zygotic Aldh2 in proper anterior–posterior axis formation, midline mesoderm specification, neural tube and fin development (Gibert et al., 2006; Hamade et al., 2006; Keegan et al., 2005; Begemann et al., 2004; Begemann and Meyer, 2001; Begemann et al., 2001). Treating zygotic mutants with DEAB, a competitive reversible inhibitor of all Aldhs, produced stronger endoderm phenotypes, and suggests that other Aldhs or maternal Aldh2 attenuate the zygotic endoderm phenotype (Alexa et al., 2009). To distinguish between these possibilities Alexa and colleagues used translation and splice blocking morpholinos, which produced phenotypes reminiscent of treatment with DEAB implying that Aldh2 function (presumably maternal) rather than another Aldh was compensating in the endoderm of zygotic mutants.
GART and PAICS: Purine Synthesis and Pigmentation
Purines can be produced by a ten-step enzymatic pathway or by recovery or salvage from intracellular turnover. The liver is a major site of de novo synthesis, and purines produced in the liver supplement the salvage pathways of cell types that cannot carry out de novo purine synthesis. Two mutations disrupting components of the de novo purine synthesis pathway are required zygotically for pigment synthesis, retinoblast proliferation, and cell cycle progression during eye growth (Ng et al., 2009). gart encodes phosphoribosylglycinamide formyltransferase, phosphoribosylglycinamide synthetase, which catalyzes early steps of inosine monophosphate (IMP) synthesis. Paics encodes phosphoribosylaminoimidazole carboxylase, phosphoribosylaminoimidazole succinocarboxamide synthetase, which catalyzes later steps of IMP synthesis. Some homozygous mutants escape the zygotic recessive phenotypes and develop to adulthood possibly due to utilization of the salvage pathway.
The maternal mutant phenotype reveals essential contributions for both enzymes, which cannot be compensated for entirely by zygotic function. The maternal-effect phenotype caused by loss of maternal paics is relatively mild compared to the zygotic phenotype; the progeny of mutant mothers have a normal anterior–posterior axis, but reduced pigmentation (Ng et al., 2009). The maternal zygotic phenotype is considerably stronger than the zygotic phenotype caused by paics and is characterized by a shorter anterior–posterior axis, reduction of head structures and pigmentation, and cardiac edema (Ng et al., 2009). The maternal-effect and maternal-zygotic phenotypes of gart are more severe than the maternal-effect and MZpaics phenotypes (Ng et al., 2009). These embryos show developmental delays, anterior defects, lack of pigmentation, and development arrests at 28 hours post-fertilization (Ng et al., 2009). In the future, it will be important to investigate whether the maternal defects are solely due to reduced IMP, or also involve phenotypes caused by the accumulation of substrates of the synthesis pathway. The similar zygotic phenotypes of gart and paics suggest that these defects are due to compromised IMP availability. The stronger maternal-effect phenotypes of gart indicate that accumulation of substrates may impair embryonic development, as Gart mediates earlier steps in the pathway.
Morgan & Claypool Life Sciences, San Rafael (CA)
Marlow FL. Maternal Control of Development in Vertebrates: My Mother Made Me Do It! San Rafael (CA): Morgan & Claypool Life Sciences; 2010. Compensation by Stable Maternal Proteins.