In homeotic transformation, a normal body part is replaced by a body part which is regularly found in other regions.

Different model organisms are used to study development, chosen for their: length of embryonic development: length of life cycle; size of organism; ease of lab growth; size of genome; number of chromosomes; and experimental techniques available for that organism. Embryos that develop internally are difficult to see and manipulate, as they embed into the mother’s uterus. Large embryos are easier to directly manipulate (ie, tissue transplantation). Large adult organisms are space- and money-consuming versus smaller organisms, which can be easier to analyze and in large numbers.

In Xenopus, the Nieuwkoop Center is the dorsal- and vegetal-most region. It gives rise to the Primary Organizer (aka Spemann Organizer or Spemann-Mangold Organizer), which is the region known as the dorsal lip of the blastopore (DLB). Spemann and Mangold’s experiments found that the DLB dorsalizes surrounding tissue, thus forming (along with the SEP) the dorsal-ventral axis. In addition to dorsalizing surrounding tissue, the Primary Organizer: fates overlying ectoderm as neural plate tissue; and is determined to be notochord tissue. Dorsalized tissue gives rise to somites and pronephric tubules.

The DLB uses induction (interaction with adjacent cells) via secreted diffusible signals. A cell that can be induced is competent; embryonic tissues are only competent during gastrulation. The use of diffusible substances was proven when dorsal lip tissue and ectoderm were cultured together, but separated by a filter with a 0.5µm pore; the ectoderm was induced into neural tissue, despite no cell processes seen to pass through the filter. Dr. DeRobertis identified genes expressed only in the organizer via differential screening of Xenopus dorsal lips. Direct purification was ineffective because the hypersensitive ectoderm overlying the chordamesoderm was induced by even unnatural substances. Organizer-specific gene products are divided into two groups:

But How Does It All Work?

The primary organizer arises in the dorsal marginal zone via induction by the Nieuwkoop center. The Nieuwkoop center arises in the dorsal vegetal zone due to a gradient of nodal-related proteins (for frogs, Xenopus nodal-related or Xnr). The marginal zone involutes at the DLB during gastrulation to give rise to the mesoderm.

Notice that this figure (multi-cellular) differs from the one immediately above (single-cell) in that the dorsal-ventral axis is now horizontal.

Methods to identify genes for early Xenopus embryo D/V and A/P patterning include: differential screening (aka subtractive hybridization) to identify genes expressed at specific times and places, as with the egg vegetal pole and early gastrula organizer tissue; testing Xenopus homologs of mammalian cell signaling genes for ability to induce mesoderm in isolated animal caps; and testing cloned mRNAs for ability, when injected, to induce a new axis. After identifying relevant genes, their role was assessed by injecting into the one- or two-cell embryo the corresponding mRNA, antisense DNA olignucloetides, RNAi or dominant negative or active DNA construct of the gene. After this injection, the embryo is examined whether it does or does not form an axis (dorsalize).

At the 8-cell stage, the mammalian embryo undergoes compaction where the spherical and loose blastomeres nestle tight together to establish new cell junctions and form a blastocyst. The blastocyst has an outer trophoblast layer (responsible for implantation into the uterine wall) and an inner cell mass placed eccentrically within the blastocoel. The inner cell mass gives rise to the embryonic epiblast (from which the embryo arises), the overlying amniotic ectoderm (separated from the epiblast by the amniotic cavity) and the underlying hypoblast. The mammalian blastocyst is analogous in structure to the yolky bird embryo, without the yolk.

Intrinsic (aka cytoplasmic) and extrinsic determinants coexist, as shown by two (respective) urchin blastula experiments. Removing the progenitor cell of mesoderm from an urchin blastula results in a mesoderm-lacking larva. However, sagittally halving an entire blastula will result in a normal larva. The phenom of extrinsic determinants is known as regulative development.

The end result of gastrulation is the transformation of the blastula, which consists of a ball or disc of relatively undifferentiated cells into an embryo that contains three germ layers.

The mode of gastrulation depends on the distribution of yolk, but all different types of gastrulation are related to each other in that they are different ways for cells on the outside to get inside (via different types of rearrangement and movement) to form the three germ layers. The cytoskeleton (microfilaments and microtubules) and extracellular matrix play a critical role in providing the motive force and the cues for gastrulation. The position at which gastrulation occurs is determined by local production of a signal that activates small GTPases like Rho, which reorganize the cytoskeleton locally.

During gastrulation, the blastula transforms and the cells begin to manifest their different fates. By the end of gastrulation, three different germ layers have formed: ectoderm (outer); mesoderm (middle); and endoderm (inside). Different cell types arise from these germ layers.

Note that all three germ layers are derived from the epiblast. Furthermore, epithelium is derived from all three germ layers: endoderm (epithelial lining inside viscera); mesoderm (mesothelial lining outside of viscera); and ectoderm (skin epithelium).

Development of placodes in the epithelium involves multiple inductive interactions. In the case of the sensory placodes, the neural tissue induces placode formation. In the case of ectodermal appendages, the mesenchyme is a source of inductive signals. In all cases, there is reciprocal signaling between the epithelium and the mesenchyme. In addition to positive signals that induce placode formation (Shh, Wnts, FGFs, BMP antagonists), there are negative signals (such as BMPs) that are important for allowing spacing of ectodermal appendages like teeth and hair follicles.

The developing brain induces the overlying ectoderm to develop into sensory organs. The neural crest arises at the posterior border of the neural plate and the epidermis; ectodermal placodes arise at the anterior border of the neural plate and the epidermis. VIa invagination, ectodermal places then develop into ganglia (nerve bundles) and parts of the ear, eye and nose (sensory organs of the head).

1. Ectodermal placodes arise from cells at the border of the neural plate and the epidermis in anterior regions of the embryo (in the posterior region, this same border gives rise to the neural crest).
2. The brain induces development of two dorsolateral rows of ectodermal placodes in the head. The rhombencephalon induces the otic placode — the first ectodermal placode to develop — whose invagination forms the inner ear. The telencephalon induces the nasal placodes, whose invagination ultimately connects to the oral cavity. The diencephalon induces the lens placode, whose invagination is part of eye development.

Ectoderm Dysplasia

Epithelial placodes do not properly develop in Individuals with ectodermal dysplasia, thus retarding development of ectodermal appendages. Mice and humans with ectodermal dysplasia have little or no hair, fewer and smaller teeth, few or no sweat glands and small nails. Cloning of mutated genes in ectodermal dysplasia patients led to the discovery of a secreted factor called ectodysplasin-A (EDA) and its receptor (EDAR). EDA is expressed throughout the epidermis, and EDAR is induced by signals from the mesenchyme (dermis). Islands of EDAR expression are induced by further signals to grow downward into the mesoderm and form placodes.

Epidermal ectoderm gives rise to teeth, hair, nails, mammary glands, scales and feathers. Via epithelio-mesenchymal interaction, underlying mesenchyme determines which structures are formed from the epidermis. For example, if chicken thigh mesoderm is grafted beneath wing ectoderm, then the wing ectoderm will form thigh feathers rather than wing feathers. Epithelio-mesenchymal interaction occurs in three steps:

In birds and mammals, the endoderm is a disk that invaginates, starting at its anterior and posterior ends, to form a closed epithelial cylinder surrounded by a thin layer of splanchnic mesoderm. The splanchnic mesoderm later becomes smooth muscle. The endoderm gives rise to the pancreas, liver and lungs via branching of endodermal tubes. Regional morphological differences amongst epithelial cells demarcates the three endodermal segments, each of which evaginate:

Cancer

Regulation of the constant rapid division in the intestine is import to avoid cancer. Intestinal cell differentiation depends on Cdx2 expression. If cells do not differentiate correctly, they continue to proliferate. As expected, Cdx2^+/- knockout mice develop colon tumors at a high rate. Defects in the APC gene (encoding adenomatous polyposis coli or APC) are the most common cause of human colorectal cancer. APC targets β-catenin for degradation; β-catenin interacts with TCF/LEF factors in the Wnt signaling pathway, which maintains stem cell proliferation. APC defects reduce β-catenin degradation, causing excessive Wnt signaling and thus overabundant proliferation. Similarly, colorectal cancers sometimes arise from mutations that stabilize β-catenin or increase TCL/LEF factor levels.

Development of endodermal organs is dependent on interaction between the endoderm and the surrounding mesoderm. Endodermal tissue cultured in vitro does not differentiate without its surrounding mesoderm; endodermal tissue co-cultured in vitro with splanchnic mesoderm undergoes organ-specific differentiation. Furthermore, organ development depended on the position of the mesoderm — not the endoderm — along the antero-posterior axis. For example, tracheal bud endoderm cultured with mesoderm from different regins differentiates according to location from where mesoderm derived. Mesoderm fromnear liver leads to liver-like tubues in the tracheal bud. Mesoderm outside the immediate splanchnic layer also instructs the endoderm.

For example, as we will discuss in more detail below, signals from the notochord (dorsal of the endoderm) and the heart primordium (antero-ventral of the endoderm) play an essential role in the specification of the pancreas and liver, respectively. Inductive signals also pass from the endoderm to the mesoderm. In other words, signaling between the mesoderm and endoderm is reciprocal. Thus, endoderm co-cultured with somitic mesoderm (which normally forms muscle and bone) will induce the mesoderm to become smooth muscle.

Shh, TGFβ and FGF

Hedgehog, TGFβ and FGF are families of regulatory genes involved in endo-mesodermal interactions and are critical for region-specific endodermal differentiation.

The mesodermal layer of the early embryo forms as a result of gastrulation. This mesodermal layer of cells initially constitutes an epithelium; after gastrulation the cells of this epithelium lose their close association with each other (undergo an epithelial-mesenchymal transformation).

For example, we learned that the mesoderm that comes to occupy the most dorsal position in the embryo, the dorsal mesoderm, will become the notochord. Mesoderm that occupies more ventral positions go on to become other derivatives. For example, we also saw that the endoderm becomes surrounded by mesoderm, and that mesoderm is a more ventral type (the splanchnic mesoderm).

When the somite first separates from the presomitic mesoderm, it can give rise to any somite-derived structure. As the somite matures, its various regions become committed to forming certain cell types.

An axon often has to navigate great distance to reach its target cell (ie, another neuron or muscle fiber) and establish the synaptic connection. This process is axonal pathfinding. The axon does not navigate its natural pathway due to any single cue, but via combinations of signals. This redundancy makes axonal pathfinding extremely complex. Axonal pathfinding is extremely specific: a particular axon always contacts the same (or at least very similar) set of neurons or muscles.

Neurons have an intrinsic polarity that is always the same for a specific type of neuron. At one end of this polarity, a localized increase in cell membrane activity occurs (with ruffles, aka lamellipodium often visible) and fine filopodia of the cell cytoplasm extend and withdraw. The structure of filopodia is maintained by microfilaments, while axonal strucure is maintained by microtubules. Eventually, a filopodium forms a growth cone, an actively motile region at the far end.

The growth cone travels based on cues from a substrate called the extracellular matrix (ECM). The ECM contains laminin, collagen and fibronectin (the first being the most important) that adhere to cadherins and integrins in the growth cone membrane. Also, the ECM contains unique molecules (ie, nerve growth factor and retinoic acid) that guide the growth cone, sometimes across a gradient and other times along a narrow path. These unique molecules are deposited: by tissues over which the axons grow (ie, epithelia, somites and blood vessels); by cells at crucial migratory points; and even by the target tissue itself.

Once the growth cone reaches its specific target (ie, muscle fibers or another neuron) it must stop growing and establish a synaptic connection. The high specificity of axonal pathfinding is determined by any of three ways:

Netrin

Commisural neurons are interneurons in the (usually dorsal) spinal cord that extend their axons across the midline. Commisural projects project ventrally toward the floor plate, and then cross the midline ventral to the floorplate of the spinal cord. Recombination experiments have shown that the floor plate secretes netrin, an attractive signal critical for commisural axons to migrate to the floor plate and cross the midline. In netrin^-/- mutants, commisural axons fail to grow to the floor plate.

Ehprin

Ephrins are membrane-bound ligands that bind to membrane-bound ephrin-receptors called ephs. When an ephrin and an eph bind, a signal is generated in both cells — this means the signal is bi-directional. Ephins are repulsive signals in axon migration, with ephrin/eph signaling responsible for setting the retino-tectal topographic map. In a topographic map, the spatial organization of neurons in one region (retina) is replicated in a connected region (tectum). The retina and tectum contain inverse gradients of ephs and ephrins; axons extend from the retina to the tectum until reaching a signaling threshold (inversely proportionate to their starting point) that inhibits further navigation. Thus, axons from a retinal region with low levels eph will target a tectal region with high levels of eph. In the figure below, axons from a given retinal quadrant will target the tectal quadrant of matching color.

All in all, ephrin/eph signaling is critical for:

1. motor neurons extending only through the anterior of a somite;
2. setting the retino-tectal topographic map;
3. inhibiting mixing — rhombomeres, compartments in the hindbrain across which cells do not mix, express ephrins and ephs.

A critical gene that is expressed throughout the developing eye is Pax6. Mutants of Pax6 have aniridia (no iris), small eyes and even no eyes. Pax6^-/- homozygotes lack eyes and nasal cavities. Pax6 is required in the ectoderm, as shown by tissue recombination studies using Pax6^+/+ and Pax6^-/- ectoderm and optic cups. Also, ectopic expression of eyeless (the Drosophila homolog of Pax6) in Drosophila larvae causes ectopic eyes to develop on the legs and wings; murine Pax6 has a similar effect, showing its strong conservation.

FGF/Shh Signaling

Reciprocal signaling between the lung endoderm and surrounding mesenchyme controls the pattern of bronchial (lung) branching. Mesenchymal cells close to budding region produce Fgf10, which promotes proliferation of bronchioli. The tracheal bud does not branch in Fgf^-/- mice, thus confirming that FGF induces cell proliferation. However, if FGF were the only signal then the bronchioli would continually grow without branching. Several mechanisms define branch points, one of which involves Shh.

Shh inhibits FGF expression, and is secreted from the tip of the bronchiolus when branching is about to occur. This leads to a high FGF concentration along a growing bronchiolus, but a low FGF concentration at its tip. As a result, the bronchiolus splits at the tip into two branches; each new branch grows toward the high FGF concentration. Shh^-/- knockout mice have primitive sacs instead of lungs due to complete failure of branching.

Drosophila Lung Development

Drosophila has a signaling mechanism similar to the aforementioned FGF/Shh system. The Drosophila respiratory system begins as a series of invaginating placodes which later future to form multiple branches. Growth of tracheal primordia is induced by binding of its FGF receptor by an FGF homolog called branchless. The tip of the tracheal primordium expresses sprouty, which diffuses and inhibits FGF-stimulated proliferation in basal cells. This causes a T-shaped expansion of the tracheal primordium tip.

Similar to the tracheal and pancreatic buds and their branches, the hepatic (liver) bud is an evagination of the endoderm which branches profusely to form the liver.

Similar to the tracheal and hepatic buds and their branches, the peancreatic bud is an evagination of the endoderm which branches profusely to form the liver. This branched endodermal endothelium differentiates into two types of glandular tissue: exocrine glands, which produce essential digestive enzymes that are secreted into the small intestine; and endocrine glands (aka islet of Langerhans or islets) that produce the hormones insulin and glucagon.

The brain develops from the neural tube. Before even fully developing at the posterior, the neural tube (initially straight) begins to form bulges at the anterior that will give rise to the brain. First, three primary vesicles are formed; starting at the most anterior, these are the forebrain (prosencephalon), midbrain (mesencephalon) and hindbrain (rhombencephalon). Many transcription factors confer identity upon the mammalian brain, including Hox genes.

Expression of vertebrate Sonic hedgehog protein is extremely localized to the notochord and spinal cord floorplate. The floorplate forms where Sonic hedgehog levels are highest, and motor neurons form where Sonic hedgehog levels are lower; this suggests that a notochord-releaseed Sonic hedgehog protein gradient patterns at least the ventral portion of the neural tube. Addition of cells producing Sonic hedgehog has a similar effect as adding an additional notochord: an ectopic floorplate and motor neurons.

The role of Sonic hedgehog was confirmed via Shh^-/- knockout mice. Loss-of-function homozygotes die as fetuses and exhibit severe defects consistent with Sonic hedgehog’s aforementioned inductions: the floorplate of the neural tube, with mutant fetuses exhibiting cyclopia (eye and nose primordia fused along a degenerated ventral midline); and sclerotomes, with mutant fetuses lacking vertebrae and ribs.

In humans, mutant Sonic hedgehog range in severity from mild (two front incisors fused together) to severe (holoprosencephaly, leading to cyclopia and a single front hemisphere of the brain. Different individuals with the same mutation can have different phenotypes, suggesting that modifying genes affect the severity of the phenotype. The fetus’ prenatal environment may also impact the phenotype.

Read about Sonic hedgehog in lung development, where Shh inhibits FGF expression and FGF induces cell proliferation.

We have seen that the ZPA produces Shh and controls A/P identity.
The PZ and AER control P/D outgrowth.
The PZ produces FGF10 and the AER produces FGF8.

The new concept I want to introduce is that these signaling centers interact to maintain each other. For example, in addition to controlling A/P identity, Shh also acts on the PZ to to maintain its survival.
Similarly, the FGF10 produced by the PZ maintains the AER.
Finally, the FGF8 produced by the AER acts on both the PZ and the ZPA to maintain these structures.

1. Removal of AER stops formation of distal structures

2. Removal of AER causes loss of ZPA activity

3. Replacement of PZ mesoderm with flank
mesoderm causes degeneration of AER

4. Removal of ZPA causes loss of formation of distal structures (i.e. PZ activity and AER activity)

There are some experiments that tell us that the PZ, AER, and ZPA interact to maintain each other.

For example, we have seen that removal of AER blocks formation of distal structures. This suggests it is required to maintain the PZ.
Next, removal of the Aer also causes a loss of ZPA activity. Shh expression is lost. This shows the AER is required to maintain the ZPA.

The role of the PZ on maintaining the AER can be seen if we replace the PZ mesoderm with other flank mesoderm. This other mesoderm is unable to maintain the AER.

Finally, removal of the ZPA causes a loss in the formation of distal structures.

To review, as I mentioned earlier, the limb bud consists of mesenchymal cells arising from the lateral plate mesoderm, and an epithelial covering coming from the ectoderm. It is at this early stage of development, before any cell differentiation takes place, that different parts of the limb bud begin to produce signals that control development along the P/D and A/P axes. The basic point here is that these signaling sends transmit information to cells in the limb bud at an early stage of development, and it isn’t until much later that cells start to differentiate into different skeletal elements at specific locations, depending on the signals they received earlier.

Evidence for existence of a “prepattern”: digits can form in absence of polarizing activity
A final feature I want to mention to you is that the ability of the limb mesenchyme to form segmented structures is instrinsic to the limb bud cells themselves. If we take the cells, diserse them so that we no longer have any gradients of FGF or Shh, and then put them back into an ectodermal limb jacket, a disorganized limb will grow out, but what is striking is that it has recognizable digits composed on individual bones. So the e ability to form a repeated segmental structure is present and doesn’t involve gradients of the patterning molecules we already discussed. This is somewhat reminiscient of the situation with the somites, where we saw the somite formation occurs due to an oscillation of a negative feedback pathway.

Picture 7

Generating Periodic Structures
Reaction-diffusion mechanisms: a form of lateral inhibition established by negative feedback loops.
Observations of this sort have led to the theory that reaction-diffusion mechanisms are involved. These are related to the negative feedback pathway we discussed for somite formation.
The difference is in the reaction diffusion mechanism, the activator protein that gets induced is stable, but it forms a concentration gradient.

Forelimb vs Hindlimb is determined by Tbx = T box (DNA binding domain) transcription factor. Tbx5 determines wing bud and Tbx4 determines leg bud. In the previous slide, we saw that the mesoderm differentiates according to its own developmental program, which was to make leg structures. The positional signals for regional identity must be present in the mesoderm. This implies that there is differential gene expression in wing vs leg.

Whether a hindlimb or forelimb develops is determined very early, by the time a limb bud is evident. The identity will be under the control of Hox genes, since limb identity depends on where on the AP axis the limb bud develops.

Limb identity is determined by the ability of Hox genes to activate the expression of Tbx genes. These are transcription factors. The Tbx genes that control limb identity are Tbx4 and Tbx5.

Now we’ll look at some experiments that demonstrate that Tbx genes control limb identity.
One way to look at this is to induce an ectopic limb to see what type of limb develops, either forelimb or hindlimb, and then to correlate that with the expression of Tbx4 or Tbx5.
In this experiment, a limb bud can be induced in the lateral plate mesoderm by implantation of a bead soaked in FGF. In this case, the bead is implanted in a location where Tbx5 is induced, and the limb develops as a wing.

However, infecting lateral mesoderm with a virus that causes overexpression of Tbx4 will override the normal course of development by altering expression patterns of Tbx genes. Tbx4 is overexpressed in the flank mesoderm by introducing a vector containing a Tbx4 gene. The limb but that now deelops expressed high levels of Tbx4, the gene normally expressed in hindlimb bud. The wing bud now develops into a leg instead of a wing.

We have seen that the PZ controls P-D identity. This must involve differential gene expression. We have already seen that Hox genes control identity along the A/P axis of the embryo and the positioning of the limb buds. They also control identity along the P/D and A/P axis in the limb.

The expression patterns change during development. However, if we look at the expression of Hoxa9 through Hoxa13 in an early limb bud, we can see a colinearity of expression, with the most distal regions expressing the most members of the complex.

Evidence that Hox genes are involved in P/D patterning comes from looking at the phenotypes of mice in which Hox genes are knocked out. For example, were is a normal mouse forelimb. In this mutant, all of the Hox11 genes (hoxa11, d11,etc) are defective. As a result of having no normal Hox11, the foreleg (radius and ulna are almost completely missing).

What we don’t see are homeotic transformations.

Here is an example of a Hox mutation in humans. As we saw in the previous slide, Hoxa13 is expressed in the most distal cells in the limb. In people lacking hoxa13, it is the most distal elements, the digits, that are affected. The types of malformations are complicated and not understood on a molecular level.

What is important is not the type of malformation, but rather the type of structure that is affected by a particular Hox mutation. So, the Hox genes that show the most distally restricted expression affect the most distal limb elements. Hox genes like Hoxd11 that show a more proximal range of expression affect more proximal structures.

Maternal effect genes are transcribed, and their mRNA translocated into the egg, during oogenesis. Maternal effect genes acts before any zygotic genes, which are encoded by the embryonic genome itself. The maternal phenotype determines the zygotic phenotype. Thus, a MEG^+/- female will have all normal children even if the child’s phenotype is MEG^-/- (due to mating with a MEG^+/- male or MEG^-/-). However, a MEG^-/- female will be unable to have normal children because embryonic development will be defective. There are forty maternal effect genes in Drosophila, including:

A spacially restricted ligand activates the Torso RTK, which then initiates a phosphorylation cascade — involving Ras, Raf-1, MAP kinase kinase (MAPKK, aka MEK) and then MAP kinase (MAPK) — that inactivates transcriptional repressors at the two poles of the embryo. This is critical for terminal formation. Where RTK is most activated, huckebein and tailless transcription is activated; extending to where activation is reduced, tailless transcription (encoding tailless) is still activated.

How Does Sxl Work?

Sex-lethal is a sequence-specific RNA binding protein that recognizes a specific UGUUUUUUU element in its target RNAs. It has a Β1,2,3 & 4 domains as well as RNA recognition motifs RRM1 and RRM2. The presence or absence of Sxl in an early embryo will determine whether it develops as a male or a female.

Sxl and Tra

The female produced Sex-lethal protein also regulates splicing of Transformer (Tra), the next gene downstream in the Sexual Differentiation Pathway.

An exon in Tra pre-mRNA has two 3’ splice sites. U2AF has higher affinity for the primary upstream 3’ splice site, so splicing occurs there. However, this polypyrimidine tract also contains a high affinity Sxl binding element allowing Sxl to bind if it is present.

Gametogenesis is the development of germ cells into gametes. Gametes are large nonmotile oocytes in females, and small motile sperm in males. Gametogenesis occurs in the gonads: ovaries in females and testes in males. The two main differences between oogenesis and spermatogenesis: prophase arrest; and unequal division.

The egg must provide a nucleus (genetic informatino), specific regulatory molecules (mRNAs, cytoplasmic determinants) that interact with nuclei, and building materials for development (protein, carbon source) until the embryo’s feeding or placental stage. The volume of the egg can range from 10³ (mammals, sea urchin) to 10⁶ (amphibian) to 10¹¹ (ostrich egg) times larger than a somatic cell. A normal-size oogonium gives rise to such an enormous ova by conserving cytoplasm during meiosis and also undergoing a massive growth phase. Except for gas and limited ion and water exchange, the egg is a closed system. Thus, embryogenesis uses only macromolecules from within the egg itself (formed during oogenesis) until the embryo is developed enough to feed itself or can draw from the mother via a placenta. Common features of oogenesis are: the uptake of yolk from a source outside the oocyte; a high level of transcription of mRNA; and the presence of follicle cells. Features specific to oogenesis in only some organisms are: nurse cells; and DNA amplification. The components of the egg that must be synthesized during oogenesis are:

A sperm’s role is to deliver a male’s nucleus (namely, the genetic information within) to the egg. Mature sperm lack ribosomes and mRNA; they are transcriptionally and translationally inactive.

In Drosophila, the dorsal-ventral patterning system causes a ventro-lateral portion of the blastoderm layer to become committed to a neurectodermal fate. The presumptive neurectodermal cells develop from nuclei that contain moderate levels of nuclear dorsal protein. Following cellularization of the blastoderm and the onset of zygotic gene expression, these cells express Sog, an inhibitor of DPP. The neurectoderm in the Drosophila embryo consists of two lateral stripes on either side of the embryo. These stripes are separated ventrally by the presumptive mesoderm (twist-expressing cells). Following invagination and internalization of the mesoderm, the presumptive neurectoderm comes to occupy the most ventral position in the embryo.

Hox genes and head gap genes