F26 AnimalDevBio Unit 1 Part 2: Fertilization, Cleavage, Gastrulation, and Embryonic Patterning

Gamete Anatomy, Ciliary Architecture, and Sperm Capacitation

• Sperm Structural Organization:

  • Sperm Head:

  • Acrosomal Vesicle: Contains hydrolytic enzymes and proteasomes that digest complex sugars and protein coats surrounding the oocyte, facilitating sperm entry.

  • Haploid Nucleus: Contains the condensed paternal genetic material.

  • Midpiece:

  • Axoneme: Motor component of the flagellum. Consists of a central pair of single microtubules surrounded by an outer ring of nine doublet microtubules, composed of tubulin protein (the canonical $9+2$ axonemal arrangement).

  • Dynein: Axonemal motor protein with ATPase activity. Dynein hydrolyzes ATP to generate mechanical sliding force between adjacent microtubule doublets, inducing flagellar bending.

  • Centriole: Acts as the microtubule-organizing center and origin site for axoneme assembly.

  • Mitochondria: Spiral array located in the midpiece, providing ATP via oxidative phosphorylation to fuel flagellar motility.

  • Tail and Endpiece: Responsible for generating a back-and-forth lashing movement driven by the rhythmic, coordinated sliding of doublet microtubules within the axoneme.

• Axonemal Variations in Cilia:

  • $9+0$ Axoneme Arrangement: Found in non-motile primary cilia (e.g., primary cilium). Lacks central singlet microtubules, dynein arms, and radial spokes; functions primarily in sensory signaling.

  • $9+2$ Axoneme Arrangement: Found in motile cilia and sperm flagella. Features nine outer doublet microtubules, two central singlet microtubules, inner and outer dynein arms, and radial spokes linking outer doublets to the central pair.

• Mammalian Sperm Capacitation:

  • Ejaculated mammalian spermatozoa are incapable of fertilizing an oocyte immediately upon ejaculation. They must undergo biochemical maturation termed capacitation within the female reproductive tract (uterus and Fallopian tubes/oviduct).

  • Molecular Changes During Capacitation:

  • Cholesterol Efflux: Female tract fluids strip cholesterol from the sperm plasma membrane, altering membrane fluidity and clustering acrosomal enzymes.

  • Receptor Unmasking: Removal of seminal plasma protein coatings (orange halos) exposes underlying surface receptors (yellow T-structures) required for binding the zona pellucida.

  • $\text{Ca}^{2+}$ Influx: Intracellular calcium levels rise, triggering hyperactivated motility (whiplash flagellar beating) and priming the sperm for the acrosome reaction.

  • Epididymal Transit: Sperm mature during transit through the highly convoluted epididymis before reaching the vas deferens, where they gain initial potential motility prior to mixing with seminal plasma during ejaculation.

Mechanics of Sperm Guidance

• External Fertilization Guidance (Sea Urchins):

  • Environmental Challenge: Gametes are released into massive volumes of open sea water, requiring mechanisms to find an egg and ensure species specificity.

  • Chemotaxis: Eggs release species-specific Sperm-Activating Peptides (SAPs), such as Resact (a $14$ -amino-acid peptide in sea urchins).

  • Sperm express membrane receptors specific for SAPs. Binding triggers a directional swimming response up the concentration gradient toward the egg within seconds ($0\text{ s}$ to $90\text{ s}$ post-release).

• Internal Fertilization Guidance (Mammals):

  • Environmental Challenge: Approximately $300 \times 10^6$ sperm enter the vagina, but only about $1\text{ in }10^6$ ($\sim 300$ sperm) successfully reach the ampulla of the Fallopian tube.

  • Sequential Navigational Mechanisms:

  1. Uterine Muscle Contractions: Muscle contractions propel sperm long distances through the uterus.

  2. Rheotaxis: Coitus stimulates fluid flow from the oviduct toward the uterus. Sperm sense fluid shear stress and orient themselves to swim upstream against the current (long-range guidance).

  3. Thermotaxis: Sperm swim along a thermal gradient (warmer ampulla vs. cooler isthmus) over intermediate distances.

  4. Chemotaxis: Short-range attraction mediated by follicular fluid molecules released by the oocyte-cumulus complex.

Gamete Binding, Acrosome Reaction, and Polyspermy Prevention

• Core Events of Fertilization:

  1. Contact and species-specific recognition between sperm and egg.

  2. Regulation of sperm entry to prevent polyspermy.

  3. Fusion of sperm and egg genetic material (pronuclei).

  4. Activation of egg metabolism to initiate development.

• Mammalian Egg Envelope Structures:

  • Cumulus Oophorus: Layer of follicular cells embedded in a hyaluronic acid matrix surrounding the mammalian oocyte (analogue of the sea urchin jelly layer).

  • Zona Pellucida (ZP): Extracellular matrix layer composed of glycoproteins (e.g., $ZP1$, $ZP2$, $ZP3$) surrounding the oocyte plasma membrane (analogue of the sea urchin vitelline envelope).

• Fertilization Cone Formation:

  • Upon initial sperm-egg plasma membrane contact, the egg cytoplasm bulges outward to form a fertilization cone.

  • Actomyosin filament contractions within the fertilization cone engulf and retract the sperm nucleus and midpiece into the egg interior.

• Acrosome Reaction and Membrane Fusion:

  • Binding to cumulus or zona pellucida proteins induces exocytosis of the acrosomal vesicle, releasing acrosomal enzymes (proteases and glycosidases) that digest a path through the zona pellucida.

  • Fusion Proteins:

  • Mammals: Izumo (located on the equatorial region of acrosome-reacted mature sperm) binds Juno (and CD9) on the oocyte membrane, stabilizing membrane adhesion and enabling fusion.

  • Sea Urchins: Bindin on the acrosomal process interacts with specific vitelline surface receptors.

• Fast Block to Polyspermy:

  • Mechanism: Electrical depolarization of the egg plasma membrane. Sperm-egg binding triggers an influx of sodium ions ($\text{Na}^+$), shifting membrane potential from approximately $-70\text{ mV}$ to $+20\text{ mV}$ within $1\text{ s}$.

  • Duration & Species Occurrence: Lasts for approximately $1\text{ min}$. Highly prevalent in marine invertebrates (sea urchins); uncommon or non-existent in mammals, where small sperm numbers reaching the oviduct minimize polyspermic risk.

• Slow Block to Polyspermy (Cortical Granule Reaction):

  • Mechanism: Sperm entry stimulates an intracellular wave of free calcium ($\text{Ca}^{2+}$) originating at the site of sperm contact.

  • Increased intracellular $\text{Ca}^{2+}$ drives exocytosis of cortical granules beneath the egg plasma membrane.

  • Released enzymes modify zona pellucida proteins ($ZP2$ cleavage and $ZP3$ inactivation), permanently preventing further sperm binding or penetration.

Pronuclear Fusion and Metabolic Activation

• Pronuclear Fusion and Mitochondrial Inheritance:

  • Following entry, the sperm nuclear envelope breaks down, and chromatin decondenses.

  • The sperm centriole organizes a radial array of microtubules (sperm aster) that guides the sperm pronucleus and female pronucleus toward each other.

  • Fusion of haploid male and female pronuclei forms the diploid zygote nucleus.

  • Mitochondrial Degradation: Paternal mitochondria introduced by the sperm midpiece are selectively targeted and degraded by ubiquitin-mediated autophagy. Consequently, the zygotic mitochondrial genome is derived exclusively from maternal lineage.

• Activation of Egg Metabolism:

  • The intracellular $\text{Ca}^{2+}$ wave induces metabolic activation through several cellular pathways:

  • Resumption of Meiosis: Releases the oocyte from meiotic arrest and leads to the expulsion of the second polar body.

  • MAP Kinase Inactivation: Drives the cell cycle out of meiotic arrest and releases inhibition on DNA synthesis.

  • NAD Kinase Activation: Converts $\text{NAD}^+$ to $\text{NADP}^+$, increasing $Burst$ production of $\text{NADPH}$ required for lipid biosynthesis and membrane assembly.

  • Translation Activation: Removes translational inhibitors from stored maternal messenger ribonucleoproteins (e.g., releasing repression by oocyte-specific proteins $mRNP3$ and $mRNP4$), permitting rapid protein synthesis from maternal mRNAs.

• Comparative Timeline of Fertilization Events (Sea Urchin vs. Human):

Cleavage Patterns and Egg Yolk Classification

• General Dynamics of Cleavage:

  • Rapid mitotic divisions immediately following fertilization without intervening cell growth phases ($G_1$ and $G_2$ are absent).

  • Nuclear divisions occur without increasing total embryonic volume; cytoplasm is divided into progressively smaller cells called blastomeres.

  • Early cleavage divisions (first $3\text{ to }12$ cell cycles) rely entirely on stored maternal mRNAs, proteins, and nutrient reserves, without zygotic gene transcription.

• Egg Types Based on Yolk Content and Distribution:

  • Isolecithal: Sparse, evenly distributed yolk (e.g., sea urchins, mammals/mice).

  • Mesolecithal: Moderate amount of yolk, concentrated at the vegetal pole (e.g., amphibians/frogs).

  • Telolecithal: Dense yolk occupying almost the entire egg, restricting cleavage to a small disk of cytoplasm at the animal pole (e.g., fish, birds, reptiles).

  • Centrolecithal: Yolk concentrated centrally, surrounding cytoplasm located at the periphery (e.g., insects/Drosophila).

• Cleavage Categories:

  • Holoblastic (Complete) Cleavage: Cleavage furrow extends through the entire egg.

  • Radial Holoblastic: Blastomeres sit directly on top of one another in stacked tiers (e.g., sea urchins, amphibians).

  • Spiral Holoblastic: Blastomere cleavage planes are oblique, producing staggered tiers (e.g., mollusks/snails, annelids/worms).

  • Meroblastic (Incomplete/Partial) Cleavage: Cleavage furrows cannot penetrate dense yolk mass.

  • Discoidal Meroblastic: Cleavage restricted to a disk of cytoplasm at the animal pole (e.g., fish, birds).

  • Superficial: Nuclei divide within a central syncytium and migrate to the peripheral cytoplasm (e.g., Drosophila).

• Comparison of Radial and Spiral Cleavage:

Blastula Formation, Mammalian Implantation, and Placentation

• Morula Stage and Compaction:

  • Morula: Embryonic stage consisting of a solid ball of $16\text{ to }64$ blastomeres (named after morum, Latin for mulberry).

  • Compaction: In mammals at the $8\text{-cell}$ to $16\text{-cell}$ stage, blastomeres maximize cell-cell contact by forming tight junctional complexes, transforming into a smooth, compacted sphere.

• Blastula and Blastocyst Structure:

  • Blastocoel: Fluid-filled central cavity formed within the morula.

  • Blastocyst: Mammalian blastula structure, establishing the first major cell lineage differentiation:

  • Inner Cell Mass (ICM): Inner cluster of approximately $8$ cells within the morula that remains pluripotent, giving rise to the embryo proper. Expresses stemness transcription factors Sox2, Oct4, and Nanog.

  • Trophoblast (Trophectoderm): Outer single layer of epithelial cells that forms extraembryonic membranes, including the embryonic portion of the placenta (chorion).

• Mammalian Transport, Hatching, and Implantation:

  • Fertilization occurs in the ampulla of the Fallopian tube. The cleavage-stage embryo travels through the isthmus toward the uterus over several days.

  • Zona Hatching: Before implantation, the blastocyst secretes proteases to digest a hole in the zona pellucida, shedding it. Premature hatching or impaired tubal transport can cause ectopic (tubal) pregnancies (e.g., associated with Chlamydia infection).

  • In humans, implantation into the uterine endometrium begins around Day $6\text{ to }9$ post-fertilization.

• Mechanisms of Monozygotic Twinning:

  • Dizygotic (Fraternal) Twins: Ovulation and independent fertilization of two separate oocytes by two distinct sperm.

  • Monozygotic (Identical) Twins: Formed from a single fertilized egg via three potential developmental splittings:

  1. Early Cleavage Division Split ($\sim 33\%$ of identical twins): Separation of blastomeres prior to blastocyst formation. Results in dichorionic, diamniotic twins (separate placentas and separate amniotic sacs).

  2. Inner Cell Mass Split ($\sim 66\%$ of identical twins): Duplication of ICM within a single blastocyst during compaction. Results in monochorionic, diamniotic twins (shared placenta, separate amniotic sacs).

  3. Late Post-Implantation Split ($<1\%$ of identical twins): Splitting of the embryonic disc after implantation. Results in monochorionic, monoamniotic twins (shared placenta and shared amniotic sac; carries risk of conjoined twins).

• Stages of Placental Development:

  1. Implantation (Days $6\text{--}12$): Blastocyst trophoblast contacts the endometrium and differentiates into:

  • Cytotrophoblast: Inner, proliferating cellular layer providing structural stem cells.

  • Syncytiotrophoblast: Outer, multinucleated syncytial layer that invades endometrial tissue and secretes human chorionic gonadotropin (hCG) to maintain the corpus luteum.

  1. Primary Villi Formation (Days $13\text{--}15$): Cytotrophoblasts proliferate outward, forming finger-like projections into the syncytiotrophoblast layer.

  2. Secondary and Tertiary Villi (Weeks $2\text{--}3+$): Extraembryonic mesoderm invades primary villi (secondary villi), then differentiates into embryonic blood vessels (tertiary villi).

  3. Maturation and Remodeling (Weeks $4\text{--}12$): Villi branch extensively; maternal spiral arteries remodel to irrigate villous spaces with maternal blood.

  4. Full Functional Maturity (Trimesters $2\text{ and }3$): The placenta performs nutrient/gas exchange, endocrine secretion (progesterone, estrogen, human placental lactogen / hPL), and passive immune transfer of maternal antibodies.

Principles of Gastrulation and Germ Layer Fates

• Definition and Scope of Gastrulation:

  • Gastrulation is a key process during animal development in which blastomeres undergo complex spatial rearrangements.

  • Transforms a single-layered blastula into a multilayered gastrula, establishing the primary body axes (Anterior-Posterior / AP, Dorsal-Ventral / DV, Left-Right / LR) and three primary germ layers.

• Triploblastic Germ Layer Derivatives:

  • Ectoderm (Outer Layer):

  • Outer Surface: Epidermal cells of skin, hair, nails.

  • Central Nervous System: Brain and spinal cord neurons, glia.

  • Neural Crest: Pigment cells (melanocytes), facial cartilage, peripheral nervous system.

• Mesoderm (Middle Layer):

  • Dorsal Mesoderm: Notochord.

  • Paraxial Mesoderm: Somites (bone tissue, skeletal muscle, dermis).

  • Intermediate Mesoderm: Kidney tubule cells, gonads, vas deferens, genital ducts.

  • Lateral Plate Mesoderm: Circulatory system (red blood cells, heart), blood vessels, gut wall musculature.

  • Head Mesoderm: Facial muscles, connective tissue.

• Endoderm (Internal Layer):

  • Digestive Tube: Epithelial lining of stomach, intestines, liver, pancreas.

  • Pharynx: Thyroid cells, tonsils, parathyroid.

  • Respiratory Tube: Trachea, lung alveolar cells.

• Epithelial vs. Mesenchymal Cellular Behaviors:

  • Epithelium: Cells organized in tightly linked, stationary sheets or tubes; exhibit distinct apical-basal polarity and minimal extracellular matrix.

  • Mesenchyme: Loosely organized, unattached individual cells; possess migratory and invasive capacity, lack apical-basal polarity, and are surrounded by abundant extracellular matrix.

Amphibian and Fish Gastrulation

• Cortical Rotation and Symmetry Breaking in Amphibians:

  • Entry of the sperm into the animal hemisphere induces a $30^\bullet$ rotation of the outer pigmented cortical cytoplasm relative to the inner clear cytoplasm toward the sperm entry site.

  • Exposes a lighter region of cytoplasm opposite the sperm entry site termed the gray crescent.

  • Microtubule arrays organized by the sperm centriole transport Dishevelled (Dvl) protein and GSK3-Binding Protein (GBP) to the gray crescent region on the future dorsal side.

• Primary Morphogenetic Cell Movements in Amphibians:

  • Apical Constriction / Invagination: Localized narrowing of the apical surface of epithelial cells driven by actomyosin contraction, causing cells to change into shape-defined bottle cells at the dorsal marginal zone and forming the initial dorsal blastopore lip.

  • Involution: Inward movement of expanding marginal zone mesoderm and endoderm sheets, rolling over the rim of the dorsal blastopore lip to spread along the inner surface of the ectodermal blastocoel roof.

  • Epiboly: Spreading and thinning of the animal cap ectodermal sheet to completely cover the outer surface of the embryo, driven by cell proliferation, cell flattening, and radial intercalation.

  • Convergent Extension: Intercalation of mesodermal cell layers along the dorsomedial axis, causing the tissue to narrow laterally (converge) and elongate anteroposteriorly (extend).

• Discovery and Function of the Spemann-Mangold Organizer:

  • Discovered by Hans Spemann and Hilde Mangold (awarded the 1935 Nobel Prize in Physiology or Medicine).

  • The Spemann-Mangold Organizer corresponds to the dorsal lip of the blastopore in amphibians.

  • Transplantation Experiment: Transplanting the dorsal blastopore lip of a pigmented newt gastrula into the ventral marginal zone of an unpigmented host gastrula initiates a secondary invagination site, recruiting host cells and organizing a complete secondary embryonic body axis featuring a second neural tube, notochord, and somites.

• Molecular Specification of Axis and Organizer:

  • Wnt / $\beta\text{-Catenin}$ Pathway:

  • In non-dorsal regions (Wnt OFF), Glycogen Synthase Kinase 3 (GSK3) forms a destruction complex (with Axin and APC) that phosphorylates $\beta\text{-catenin}$, targeting it for proteasomal degradation.

  • On the dorsal side (Wnt ON), localized Dvl and GBP inhibit GSK3. $\beta\text{-catenin}$ accumulates, translocates into dorsal nuclei, and binds TCF transcription factors to activate dorsal gene expression.

• Nieuwkoop Center: Dorsal-most vegetal endoderm expressing high nuclear $\beta\text{-catenin}$. Functions as the "organizer of the organizer."

• Vegetal Induction: VegT mRNA (a T-box transcription factor) and Vg1 mRNA localized at the vegetal pole induce Nodal expression. Synergism between vegetal Nodal/Vg1 signals and nuclear $\beta\text{-catenin}$ induces the overlying marginal zone cells to form the Spemann-Mangold Organizer.

• Dorsal-Ventral BMP Gradient: BMP4 acts as a ventralizing signal driving ectoderm toward an epidermal fate. The Organizer secretes BMP inhibitor proteins (Chordin, Noggin, Follistatin) that bind BMP4 extracellularly, creating a gradient that permits dorsal neural tube and notochord differentiation.

  • Zebrafish (Teleost) Gastrulation:

• Meroblastic discoidal cleavage produces a blastoderm sitting atop a massive yolk cell.

• Epiboly spreads blastoderm cells over the yolk cell, mediated by the downward migration of the Yolk Syncytial Layer (YSL) and Enveloping Layer (EVL).

• Involuting epiblast cells form the hypoblast layer (future mesoderm and endoderm) along a marginal rim called the germ ring.

• Intercalation on the future dorsal side forms a localized thickening called the embryonic shield (the teleost equivalent of the Spemann-Mangold organizer / prechordal plate).

Avian Gastrulation Mechanisms

• Blastoderm Architecture in Birds:

  • Discoidal Meroblastic Cleavage: Takes place in the hen's oviduct/cloaca, restricting division to the animal pole blastodisc.

  • Subgerminal Cavity: Fluid-filled space beneath the blastoderm cells created by ion secretion.

  • Area Pellucida: Clear, single-cell-thick central layer of the blastoderm created when deeper central cells die and shed.

  • Area Opaca: Dark, multi-layered peripheral ring of blastoderm cells in contact with underlying yolk.

  • Delamination: Cells from the primary epiblast delaminate downward as individual clusters into the subgerminal cavity to form the primary hypoblast. Secondary hypoblast grows forward from the posterior margin.

• Gravity-Driven Symmetry Breaking:

  • As the fertilized egg travels through the hen's shell gland over a $20\text{-h}$ rotation, lighter yolk lipids float upward, tilting the blastoderm at a $45^\bullet$ angle.

  • The elevated margin defines the Posterior Marginal Zone (PMZ), establishing the future posterior pole where primitive streak formation begins.

  • The PMZ contains high levels of Vg1, Nodal, and Wnt signals, serving as the avian functional equivalent of the Nieuwkoop center.

• The Primitive Streak and Hensen's Node:

  • Primitive Streak: Line of invagination formed by epiblast cell convergence along the mid-sagittal plane, replacing the circular blastopore seen in amphibians.

  • Hensen's Node: Localized thickening at the anterior tip of the primitive streak; functional equivalent of the dorsal blastopore lip / Spemann-Mangold organizer.

  • Epithelial-to-Mesenchymal Transition (EMT): Epiblast cells migrating toward the primitive streak downregulate cell adhesion molecules (e.g., E-cadherin), adopt a mesenchymal morphology, and ingress individually through the primitive groove into the blastocoel space.

• Spatial Fate Mapping of Ingressing Epiblast Cells:

  • Epiblast cells remaining on the surface without ingressing form the ectoderm.

  • Cells ingressing through Hensen's node migrate anteriorly to form the pharyngeal endoderm, prechordal plate, and head notochord.

  • Cells ingressing through the anterior portion of the primitive streak give rise to somites, notochord, and internally displaced endoderm.

  • Cells ingressing through the middle and posterior streak form lateral plate mesoderm, extraembryonic mesoderm, and kidney mesoderm.

Drosophila Development and Segmentation Cascades

• Syncytial Blastoderm and Cellularization:

  • Nuclear divisions occur without cytokinesis for the first $13$ cell cycles within a shared cytoplasm, forming a syncytium ($\sim 8000$ nuclei).

  • Energids: Nuclei surrounded by islands of cytoskeletal cytoplasm migrate to the periphery of the egg at cycle $10$, forming the syncytial blastoderm.

  • Cellularization: Following cycle $13$, cell membranes invaginate inward between nuclei, enclosing individual cells to form the cellular blastoderm.

  • Pole Cells: Form at the posterior pole during early nuclear migration; designated precursors of the germline.

• Fly Gastrulation Morphogenetic Movements:

  1. Ventral Furrow Invagination: Midventral cells undergo apical constriction, forming an longitudinal invagination groove through which mesoderm folds internally.

  2. Cephalic Furrow Formation: Transverse fold separating head region from trunk.

  3. Posterior Midgut Invagination: Infolding of endoderm carrying pole cells inward.

  4. Germ Band Extension: Convergent extension movements elongate the trunk ectoderm and mesoderm along the AP axis, wrapping the germ band around the dorsal side.

  5. Germ Band Retraction and Dorsal Closure: Retraction of the extended germ band, bringing bilateral epidermal sheets together at the dorsal midline.

• Systematic Mutagenesis Screen (Heidelberg Screen):

  • Conducted by Christiane Nüsslein-Volhard, Eric Wieschaus, and Ed Lewis (awarded the 1995 Nobel Prize in Physiology or Medicine).

  • Systematically evaluated over $40{,}000$ genetic mutations in Drosophila to identify genes directing embryonic body axis patterning.

• Anterior-Posterior Genetic Cascade:

Maternal Effect Genes (Bicoid, Nanos, Hunchback, Caudal)
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Gap Genes (Hunchback, Krüppel, Giant, Knirps)
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Pair-Rule Genes (Even-skipped, Fushi tarazu)
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Segment Polarity Genes (Wingless, Engrailed, Hedgehog)
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Homeotic (Hox) Genes (Antennapedia, Bithorax Complexes)

• Maternal Effect Genes:

  • Deposited into the oocyte during oogenesis by ovarian nurse cells.

  • bicoid ($bcd$) mRNA: Localized to the anterior pole cytoplasmic cortex. Translation produces a Bicoid protein gradient (high anterior to low posterior). Acts as a transcription factor for anterior genes and a translational repressor of caudal mRNA.

  • nanos ($nos$) mRNA: Localized to the posterior pole. Translation produces a Nanos protein gradient (high posterior to low anterior). Inhibits translation of uniform maternal hunchback mRNA in the posterior (in complex with Pumilio).

  • hunchback ($hb$) and caudal ($cad$) mRNAs: Uniformly distributed maternally. Translational repression produces protein gradients: Hunchback protein high anterior, Caudal protein high posterior.

• Gap Genes:

  • Expressed in broad, overlapping domains spanning $2\text{ to }3$ segment widths.

  • Regulated by maternal gradients. Examples include hunchback, Krüppel, giant, and knirps.

  • Mutants exhibit deletion of a large contiguous region of body segments (a broad "gap").

• Pair-Rule Genes:

  • Expressed in $7$ discrete, alternating transverse stripes along the AP axis in response to gap gene transcription factor combinations.

  • Examples include even-skipped (eve) and fushi tarazu (ftz).

  • Mutants lack every second parasegment (deleting alternating segmental units).

• Segment Polarity Genes:

  • Expressed after cellularization in $14$ narrow stripes (one stripe per parasegment boundary).

  • Maintain segment boundaries and establish anterior-posterior polarity within each individual segment.

  • Controlled by auto-regulatory feedback loops between Wingless (wg, Wnt signaling ligand) and Engrailed (en) / Hedgehog (hh) signaling pathways.

• Comparison of Pair-Rule and Segment Polarity Genes:

• Homeotic (Hox) Genes:

  • Master selector genes activated downstream of the segmentation cascade that assign specific anatomical identities to individual segments.

  • Arranged in two major gene complexes: the Antennapedia Complex (specifies anterior head and thoracic identities) and the Bithorax Complex (specifies posterior thoracic and abdominal identities).

  • Homeotic Mutations: Cause transformation of one body part into another (e.g., gain-of-function Antennapedia mutations cause legs to develop on the head in place of antennae).