User:Tphelpsdu/Mouse Development/sandbox

Life Cycle
Wild mice can survive to be up to four years of age though prevalence of predators often shortens the average lifespan to within two years (Miller 2002;). Mice can begin breeding 50 days after birth, with females potentially having their first estrous cycle from twenty-five to forty days from birth. Mating occurs at night and initiates ovulation in the female (Slack, 2013). Early development follows fertilization with: cleavage, gastrulation, neurulation, and axis formation. Litter sizes range from about ten to twelve pups with each pup born nude, blind, and earless about twenty days after fertilization (Wiki Mouse; Slack 2013).

Fertilization

Haploid gametes develop from meiosis of germ cells starting in embryogenesis. Post-meiosis, sperm cells have condensed their DNA and modified their organelles for fertilization. The nucleus is headed by an acrosome and tailed by centrioles, mitochondria. The overall shape of the cell is elongated; most of the cytoplasm is extended into the flagellum (source?). Egg, or oocyte, cells are arrested in metaphase II of meiosis; completion of meiosis does not occur until after fertilization (Slack, 2013). Egg cells are secreted into the oviduct following mating as cumulus cells, oocytes enveloped in a zona pellucida and surrounded by follicle cells (Slack 2013; Liu, 2014).

Following mating, sperm cells navigate to the oviduct, completing capacitation during this time (Slack, 2013). Fertilization of the oocyte occurs within the oviduct. Sperm cells bind to the zona pellucida by interacting with ZP3 and ZP2 (Slack, 2013; Howes, 2001). The initial interaction between the sperm cell and ZP3 activates the acrosomal reaction: the contents of the acrosome are released to digest the zona pellucida (Slack, 2013). Sperm-egg recognition is carried out at the egg surface with ADAM and integrin bindings (Slack, 2013). There is a preference for binding at the equatorial region, ninety degrees from the location of the first polar body; sperm binding influences cleavages at later development stages and unfavorable binding points reduces the ability to properly distribute transcription factors (Piotrowska-Nitsche, 2013). Once bound, plasma membranes of both gametes fuse and the remaining contents of the sperm are integrated into the egg.

Following fusion, intracellular calcium levels begin to oscillate and meiosis is resumed. Cortical granules are released and migrate to the plasma membrane and modifying receptors to block fusion by more sperm (Slack, 2013). A second polar body is expelled with the completion of the final meiotic division. DNA replication occurs within the paternal and maternal nucleus. The finished chromosomes align with the maternal spindle fibers prior to cleavage (Slack, 2013).

Cleavage

The developmental step after fertilization is cleavage. The zygote begins dividing into individual cells. There is no growth involved with these divisions. Forty-eight hours after fertilization, the first three cleavage have occurred. The genes that make up the zygote begin to be expressed once cleavage has resulted in two cells (Slack, 2013). The individual cells resulting from cleavage are called blastomeres. Once eight cells are reached the process of compaction begins. Compaction is important for increasing intracellular contact. Blastomeres flatten out and the embryo changes shape, looking more spherical. E-cadherin is a molecule that is heavily involved in the process of compaction(Larue, 1994). Gap junctions are formed during compaction as well, these are necessary for the diffusion of molecules in the embryo (Slack,2013).

Once compaction is complete the embryo is called a morula and is referred to as so until thirty- two cells have been reached. Cleavage continues, and the embryo will start forming a blastocoel. The blastocoel is a cavity full of fluid that begins forming after thirty-two cells are reached. For formation to begin, desmosomes and tight junctions must be present in the embryo creating a seal between the inside and outside. The embryo moves into the uterus during the process of blastocoel formation (Slack,2013). The tight junctions keep the fluid in the cavity as it expands (Echert, 2004). The blastocoel will continue expanding the embryo, into the blastocyst. The blastocyst is divided into two layers, one inner, the other outer (Slack,2013). The outer layer, the trophectoderm, contains tight junctions that help form a protective barrier over the inner layer. The inner layer is made up of the cavity fluid and a ball of cells called the inner cell mass (Morinaki, 2007). These newly formed layers will give rise to new tissues. Tissue formed in the inner cell mass is called the primitive endoderm. The trophectoderm forms two tissues, one of which is polar. The other tissue becomes polytene cells. These cells contain DNA which replicate and increase. There is no mitosis involved with this DNA replication (Slack,2013).

Gastrulation

The developmental process of gastrulation results in the embryo consisting of three layers, the ectoderm, mesoderm and endoderm. The formation of these layers all begin in the epiblast. One end of the epiblast, will give rise to what is known as the primitive streak. This streak lays out the future anterior-posterior axis. Where the primitive streak begins forming, marks the posterior end (Slack, 2013). The formation of the primitive streak also establishes the future left-right axis (Tam, 1997).

The streak is a series of cell movements that moves across the embryo from posterior to anterior. During these cell movements rapid cell division is occurring. These newly divided cells are then integrated into their respective layer. (Hegel 1995). At the anterior end of the streak, a node forms which is made up of two layers. These newly formed layers, along with the node will give rise to the body plan of the embryo later in development. (Slack, 2013).

Neurulation

Neurulation is defined as morphogenic movements within the primitive streak to form an enclosed neural tube.1 Morphogens can be defined as intracellular signals. These signals have the capability to inhibit or activate cell growth. In mice, the primitive streak extension begins on day 6.5.2 The primitive streak can be defined as cell growth to form the midline anterior-posterior axis of an embryo.2 Here, anterior and posterior are words that represent the future head and tail sites.

The anterior tip of the embryo denotes where head development will occur. To begin neurulation, the neural plate needs to develop. The neural plate will become the neural tube later on in development. To create the neural tube, the anterior cells within the primitive streak need to replicate. In order for the correct cells to replicate, an important mass of morphogens need to be inhibited.1 The inhibition morphogens are exported by a signaling center called the node. This correct cell replication causes a thickening in that region. The thickening grows into a U shape. In mice, this occurs on day 7.5 of development.2

Next, the U-shaped mass of cells needs to extend. The U-shaped mass becomes thinner and longer within the anterior region. In order to form a closed tube, the U-shaped mass needs to fold. The neural plate U is induced to fold. Morphogens are secreted by the notochord, which lay underneath the neural plate. Hinge regions are created within the neural plate and assist in the fold. The folding occurs during day 9-10 of embryo development.3 The folding that occurs due to the hinge regions allow the both ends of the neural-U, or neural folds, to touch along the dorsal midline of the neural plate.2 Fusion begins once the neural folds touch. And the neural plate is now a neural tube.

Advantages/Disadvantages

An advantage to using mice as a model organism for development is that they are easy to breed. They also don’t require a lot of space to maintain housing for them and their pups. Since mice are mammals, studying their development can provide insight to human development (Gibson, 2000). A disadvantage is that fertilization is internal (Slack, 2013). Another disadvantage is that the embryo develops inside of another organism instead of outside like other animals, who develop externally in their environment (Gibson, 2000).

Advantages to Mouse model Disadvantages to Mouse model
 * Fertilization mechanisms are more similar to humans than other model organisms
 * Lifecycles are relatively quick for mammals
 * Litters provide a larger experimental group than single births
 * Transgenic mice can be used to model human genetic defects including those that occur in embryogenesis
 * Challenges presented by internal fertilization and viviparity are also present in mouse models
 * Paternal and maternal contributions to the zygote differ from most mammals:
 * Centriole and mitochondria are maternal
 * Experiments may require more space and regulations than those on invertebrate models
 * Regulations and paperwork needed to operate on vertebrates