The Questions of Developmental Biology

These cells divide to form embryos with spinal cords, muscles, skeletons, and organs,
including beating hearts. However, development does not continue, and by day 10 or 11 (halfway
through the mouse's gestation), the parthenogenetic embryos deteriorate and become grossly
disorganized. Neither human nor mouse development can be completed solely with egg-derived
chromosomes.
The hypothesis that male and female pronuclei are different also gains support from pronuclear
transplantation experiments (Surani and Barton 1983; Surani et al. 1986; McGrath and Solter
1984). Either male or female pronuclei of recently fertilized mouse eggs can be removed and
added to other recently fertilized eggs. (The two pronuclei can be distinguished at this stage
because the female pronucleus is the one beneath the polar bodies.) Thus, zygotes with two male
or two female pronuclei can be constructed. Although embryonic cleavage occurs, neither of
these types of eggs develops to birth, whereas some control eggs (containing one male pronucleus
and one female pronucleus from different zygotes) undergoing such transplantation develop
normally (Table 7.2). Moreover, the bimaternal or bipaternal embryos cease development at the
same time as parthenogenetic embryos. Thus, although the two pronuclei are equivalent in many
animals, in mammals there are important functional differences between them.
Table 7.2. Pronuclear transplantation experiments
Class of reconstructed zygotes Operation
Number of successful transplants Number of progeny surviving
Bimaternal 339 0
Bipaternal 328 0
Control 348 18
Source: McGrath and Solter 1984.
The reason for these embryonic deaths is that in some cells, only the maternally derived
allele of certain genes is active, while in other cells, only the paternally derived allele of those
genes is functional. (In most genes, of course, the male-derived and female-derived alleles are
equivalent and are activated to the same degree in every cell. We are dealing here with exceptions
to that Mendelian rule.) For instance, insulin-like growth factor II (Igf-2) promotes the growth of
embryonic and fetal organs. In embryonic mice, the paternally derived allele of Igf-2 is active
throughout the embryo, whereas the maternally derived allele is usually inactive (except in a few
neural cells). Thus, if a mouse inherits a mutant Igf-2 allele from its mother, the mouse will
develop to a normal size (since the maternally derived allele is not expressed), but if the same
mutant allele is inherited from its father, the mouse will have stunted growth (DeChiara et al.
1991). The opposite pattern of allele expression is found for one of the receptors of Igf-2. Here,
the paternal gene for the receptor is poorly transcribed, while the maternal allele is active (Barlow
et al. 1991). The differences between the active and inactive alleles are caused by differential
methylation of DNA in the egg and sperm nuclei (see Chapter 5). Because certain
developmentally important genes are active only if they come from the sperm and others are
active only if they come from the egg, maternal and paternal pronuclei are both necessary for the
completion of mammalian development