Ch 52 — Animal Development

52.1

Fertilization

pp. 1156–1159

Development in all coelomate animals runs through the same stages: fertilization, cleavage, gastrulation, organogenesis, then axis and pattern formation. The boundaries are somewhat arbitrary because development never actually stops. Watch Stages of Animal Development: Cleavage, Gastrulation, Organogenesis on YouTube, from Professor Dave Explains Watch Animal Development: We're Just Tubes - Crash Course Biology #16 on YouTube, from CrashCourse
A group of cells, the germ line, is set aside very early so the finished adult can reproduce sexually later.
Fertilization is the union of sperm and egg. It is external in most aquatic animals and internal in most terrestrial animals, because gametes released into air would dry out.
Animals evolved ways to make gametes meet: mass spawning, timing to the lunar cycle, and courtship behaviors.
Fertilization has three parts: (1) sperm penetration and membrane fusion, (2) egg activation, (3) fusion of the two nuclei.
The sperm must cross protective coats: the chorion in insects, a jelly layer plus vitelline envelope in sea urchins and frogs, and the zona pellucida plus surrounding granulosa cells in mammals.
The acrosome is a sac between the sperm plasma membrane and its nucleus, packed with digestive enzymes. Exocytosis releases them and opens a path through the coats. Watch Acrosome Reaction in Sea Urchin on YouTube, from Hussain Biology
Sea urchin sperm polymerize actin into an acrosomal process, a projection that spans the vitelline envelope and delivers the sperm nucleus. Mouse sperm have no acrosomal process — the entire head tunnels through the zona pellucida. Watch Acrosome Reaction in Sea Urchin on YouTube, from Hussain Biology
After the two plasma membranes fuse, the sperm nucleus enters the egg cytoplasm directly; sometimes the cytoplasm bulges out to engulf the sperm head.
Sequence at the mammalian egg surface: sperm slips between granulosa cells → acrosomal enzymes degrade the zona pellucida → membranes fuse → the nucleus separates from the tail and enters → cortical granules release enzymes → the zona hardens and loses sperm receptors → no more sperm can enter → each haploid nucleus becomes a pronucleus. Watch Embryology | Fertilization, Cleavage, Blastulation on YouTube, from Ninja Nerd
The egg is metabolically quiet after ovulation. Membrane fusion causes a sharp rise in free Ca²⁺ released from internal stores. The rise begins at the sperm entry point and sweeps across the egg as a wave, taking about 30 seconds.
That Ca²⁺ works as a second messenger, changing the activity of many proteins at once — collectively egg activation.
Polyspermy is a real danger during spawning or ejaculation. Multiple sperm make a polyploid zygote with three or more chromosome sets, which is lethal in animals (in plants, polyploidy is a route to new species). Roughly 10% of human spontaneous abortions are triploid, and about 70% of those came from dispermy. Watch Cortical Reaction in Sea Urchin | Slow Blocks to Polyspermy on YouTube, from Hussain Biology
Fast block to polyspermy (electrical): the first fusion causes a rapid, brief shift in the egg's membrane potential that prevents any further sperm from fusing. Sea urchin eggs placed in low-Na⁺ seawater cannot make that shift, and polyspermy rates jump — the experiment that proved it. Watch Cortical Reaction in Sea Urchin | Slow Blocks to Polyspermy on YouTube, from Hussain Biology
Slow block to polyspermy (physical and chemical): cortical granules dump their contents between the plasma membrane and the vitelline envelope or zona pellucida, stripping the sperm receptors off the coat. In sea urchins the vitelline envelope lifts off and hardens into a fertilization envelope, helped by hyalin, which pulls water in osmotically to separate the envelope from the egg. Watch Cortical Reaction in Sea Urchin | Slow Blocks to Polyspermy on YouTube, from Hussain Biology
Some species have no dedicated block at all; they simply degrade or expel the extra sperm nuclei after entry.
Eggs of different animals are arrested at different meiotic stages when the sperm binds: primary oocyte, meiosis not begun (roundworms, clams); first meiotic metaphase (nemertean worms, some mollusks, insects, sea stars); second meiotic metaphase (lancelets, amphibians, mammals, fish); or meiosis fully complete (cnidarians, sea urchins). Sperm fusion can be the trigger that finishes meiosis.
The mammalian egg finishes meiosis producing one large egg and small polar bodies that carry off the discarded chromosome sets.
Sperm entry also rearranges cytoplasm. In tunicates it relocates pigment granules that mark future muscle regions. In amphibians it sets up bilateral symmetry: pigmented outer cytoplasm rotates toward the entry point, exposing the lighter gray crescent on the opposite side. Watch Spemann-Mangold Organizer and embryonic induction on YouTube, from Zar
The gray crescent fixes the orientation of the first cleavage division — a line from the sperm entry point through the gray crescent marks the future left–right divide of the body.
Activation also boosts protein synthesis sharply, using maternal mRNAs stockpiled in the egg during oogenesis, not new transcription.
Eggs can be activated artificially — even by pricking the membrane — leading to parthenogenesis. A few amphibian, fish, and reptile species reproduce only this way naturally.
Last step: the two haploid nuclei move together along a microtubule aster organized by a centriole brought in by the sperm, while the egg supplies the tubulin. In mammals both nuclear envelopes break down and a single new envelope forms around the combined diploid chromosome set.

52.2

Cleavage and the Blastula Stage

pp. 1160–1162

Cleavage is rapid division of the zygote into progressively smaller cells called blastomeres, with no overall increase in embryo size. Watch Embryology | Fertilization, Cleavage, Blastulation on YouTube, from Ninja Nerd
The animal pole and vegetal pole mark the two ends of the egg. Animal-pole blastomeres generally build external tissues; vegetal-pole blastomeres generally build internal tissues.
Blastula formation: outer blastomeres link with tight junctions that seal the interior off from the outside. Interior cells then pump Na⁺ into the intercellular spaces, water follows osmotically, the spaces merge into one cavity — the blastocoel — and the result is a hollow ball, the blastula (called a blastocyst in mammals). Watch Embryology | Fertilization, Cleavage, Blastulation on YouTube, from Ninja Nerd
Cleavage divisions are unusually fast because the G1 and G2 gap phases are shortened or skipped entirely.
Cleavage geometry varies enormously across phyla, but amount of yolk is the single biggest factor shaping it. Watch Stages of Animal Development: Cleavage, Gastrulation, Organogenesis on YouTube, from Professor Dave Explains
Holoblastic (complete) cleavage happens when yolk is sparse (isolecithal) or moderate and vegetal (mesolecithal): the furrow cuts all the way through the egg. Seen in mollusks, annelids, echinoderms, tunicates, amphibians, and mammals.
Holoblastic subtypes: radial (echinoderms — cells stack in neat rows), spiral (annelids, mollusks, flatworms — daughters sit at an angle over the cells below), rotational (mammals, nematodes — the second division is meridional in one cell and equatorial in the other), displaced radial (amphibians — horizontal furrows shifted toward the animal pole by the vegetal yolk).
Meroblastic (incomplete) cleavage happens when yolk is dense throughout (telolecithal) or concentrated centrally (centrolecithal): the furrow cannot cut the yolk. Discoidal in fish, reptiles, and birds (division confined to a small blastodisc on top of the yolk); syncytial in most insects.
Insect cleavage: nuclei divide repeatedly with no cytokinesis, producing a syncytial blastoderm — many nuclei sharing one cytoplasm. Diffusible morphogen gradients in that shared cytoplasm act directly on each nucleus to pattern the embryo. Nuclei then move to the periphery and membranes form around each, making a cellular blastoderm.
Sea urchin holoblastic cleavage gives a symmetric blastula of nearly equal cells around a spherical blastocoel.
Frog cleavage is asymmetric: yolk-heavy vegetal cells divide slowly and stay large, while yolk-poor animal cells divide fast and stay small. The result is an off-center (eccentric) blastocoel displaced toward the animal pole.
Reptile, bird, and some fish eggs are almost entirely yolk, with cytoplasm confined to a small blastodisc at one pole. Cleavage stays inside that disc and the yolk never divides, leaving a thin cap of cells sitting on the yolk mass.
Mammalian cleavage is holoblastic (there is almost no yolk) yet still echoes reptile and bird development. It produces a blastocyst: a single-cell-thick outer layer around a fluid-filled blastocoel, plus an inner cell mass (ICM) at one pole. Watch Reproductive System, Part 4 - Pregnancy & Development: Crash Course Anatomy & Physiology #43 on YouTube, from CrashCourse
The ICM is the counterpart of the reptile/bird blastodisc and forms the actual embryo. The outer trophoblast corresponds to the membrane-forming cells under a reptile shell; part of it invades the endometrium and helps build the placenta.
Commitment of blastomeres varies. Mosaic development: cytoplasmic determinants segregated unevenly during cleavage assign each blastomere a specific fate. Tunicate experiments show it — destroy a committed cell and the embryo simply lacks the structures that cell would have made.
Regulative development in mammals: early blastomeres are not committed. Take one cell from an 8-cell human embryo (preimplantation genetic diagnosis) and the remaining 7 still make a whole individual. Splitting an embryo makes identical twins. Mammalian body form therefore depends on cell–cell interactions, not inherited maternal determinants.
The earliest mammalian patterning happens before implantation. At the 8-cell stage, outer blastomere surfaces flatten against each other — compaction — which polarizes the cells. Polarized cells divide asymmetrically: cells ending up inside usually become ICM, cells left outside usually become trophoblast.

52.3

Gastrulation and the Extraembryonic Membranes

pp. 1163–1166

Gastrulation converts the blastula into a bilaterally symmetrical embryo with a central primitive gut and defined anterior–posterior and dorsal–ventral axes, and it creates the three germ layers. Watch Embryology | Gastrulation on YouTube, from Ninja Nerd
THE GERM LAYER TABLE — learn it cold. Ectoderm → epidermis of the skin, nervous system, sense organs. Mesoderm → skeleton, muscles, blood vessels, heart, blood, gonads, kidneys, dermis of the skin. Endoderm → lining of the digestive and respiratory tracts, liver, pancreas, thymus, thyroid. Watch Germ layer derivatives | Behavior | MCAT | Khan Academy on YouTube, from khanacademymedicine
Fuller ectoderm list: epidermis, hair, lens of the eye, inner ear, and — in chordates — the dorsal nerve cord that becomes brain, spinal cord, and spinal nerves, plus the vertebrate-only neural crest (gill arches, sensory ganglia, Schwann cells, adrenal medulla). Watch Germ layer derivatives | Behavior | MCAT | Khan Academy on YouTube, from khanacademymedicine Watch Embryology of Nervous System - Neurulation - Neural Tube & Neural Crest - Embryonic Disc Folding on YouTube, from Medicosis Perfectionalis
Fuller mesoderm list: notochord, linings of the thoracic and abdominal cavities and coverings of internal organs, circulatory system (blood, vessels, heart), gonads, kidneys, and somites (dermis, skeleton, striated muscle). Watch Germ layer derivatives | Behavior | MCAT | Khan Academy on YouTube, from khanacademymedicine
Cells move using lamellipodia (broad actin-filled sheets for crawling over neighbors) and filopodia (thin probes that feel out a surface, then retract to pull the cell forward). Contracting actin filaments drive most shape changes. Cells joined by desmosomes or adherens junctions move as whole sheets.
Which movement dominates depends on yolk. Low-yolk hollow blastulas use invagination (the vegetal sheet dents inward). Large yolky embryos use involution (sheets roll inward over the basal surface of the outer cells). Single cells can break away and crawl alone — ingression. Birds and mammals begin with delamination, one sheet splitting into two. Watch Embryology | Gastrulation on YouTube, from Ninja Nerd
Migrating cells carry surface glycoproteins that bind matching molecules on other cells or in the matrix, so changing cell adhesiveness is a central gastrulation event. Fibronectin and its integrin receptors are essential in many species.
Sea urchin gastrulation: vegetal surface cells flatten into a vegetal plate; some detach and ingress into the blastocoel as primary mesenchyme cells (PMCs) — the future mesoderm — migrating on filopodia to the ventrolateral corners, where they build the larval skeleton. Watch Embryology | Gastrulation on YouTube, from Ninja Nerd
The remaining vegetal plate then invaginates, forming an inward tube — the archenteron, the future digestive tube — that extends until it touches the far wall. Its opening is the blastopore, which becomes the anus; a second opening forms where the archenteron meets the opposite wall and becomes the mouth. Anus first = deuterostome.
Frog gastrulation is harder because yolk is unevenly distributed. A crescent-shaped slit of invaginating cells starts the blastopore. Animal-pole cells involute over the dorsal lip, which forms exactly where the gray crescent was in the fertilized egg. Watch Spemann-Mangold Organizer and embryonic induction on YouTube, from Zar
The involuting layer pushes inward until it meets the far wall, erasing the blastocoel and creating the archenteron. Yolk-rich cells bulge in the opening as the yolk plug, sitting between the dorsal and ventral lips.
Frog germ layers: the outer layer is ectoderm, the inner layer is endoderm, and cells that involute over both lips migrate between them to form mesoderm.
Bird and reptile gastrulation: after cleavage the embryo is a blastoderm cap on a huge yolk. It delaminates into two layers with a blastocoel between them. All cells of the embryo proper come from the upper layer; the lower layer makes only extraembryonic tissue.
Upper-layer cells migrate to the midline, break away, and ingress — creating the primitive streak, functionally an elongated blastopore. Cells that migrate through and displace the lower layer become endoderm; cells that move laterally become mesoderm; cells that never enter the streak stay ectoderm. Watch Embryology | Gastrulation on YouTube, from Ninja Nerd
Mammalian gastrulation copies the bird almost exactly even though there is no yolk mass — the flattened ICM plays the role of the blastoderm. The placenta made real yolk unnecessary, but the embryo still gastrulates as if it were sitting on a yolk ball, and still builds a yolk sac from cells lining the blastocoel.
Mammalian sequence: an amniotic cavity opens between the ICM and the embryo pole; the ICM flattens and delaminates into future ectoderm and endoderm; lower-layer cells line the blastocoel as the yolk sac; a primitive streak forms in the ectoderm and mesoderm-fated cells migrate inward through it.
Extraembryonic membranes are the key adaptation for reproducing on dry land in reptiles, birds, and mammals. They are made from embryonic cells but lie outside the embryo's body. There are four: amnion, chorion, yolk sac, allantois. Watch Extraembryonic Membranes on YouTube, from Educator.com
Amnion: the inner membrane that surrounds the embryo and suspends it in amniotic fluid, recreating the aquatic environment of fish and amphibian embryos. Watch Extraembryonic Membranes on YouTube, from Educator.com
Chorion: the outermost membrane, sitting against the eggshell in birds and separated from the other membranes by the extraembryonic coelom. In mammals it comes from the trophoblast and its contact zone with the endometrium becomes the fetal half of the placenta. Watch Extraembryonic Membranes on YouTube, from Educator.com
Yolk sac: the critical nutrition source for bird and reptile embryos. Mammals still form one, but it is not nutritive. Watch Extraembryonic Membranes on YouTube, from Educator.com
Allantois: in birds it is an outpouching of the gut that stores uric acid waste, then expands and fuses with the chorion to make the chorioallantoic membrane, which brings embryonic blood vessels up against the porous shell for gas exchange. In mammals the allantois contributes the blood vessels of the umbilical cord. Watch Extraembryonic Membranes on YouTube, from Educator.com

52.4

Organogenesis

pp. 1167–1171

Organogenesis is the formation of organs in the correct locations from interacting germ layers. It follows gastrulation immediately and often begins before gastrulation is finished.
Drosophila is a useful model because morphogen gradients already set up the anterior–posterior and dorsal–ventral axes, giving a coordinate system that positions each organ.
Salivary glands form as tube-like invaginations of ectoderm on the ventral surface of the third head segment. They only arise from an anterior strip of cells expressing Sex combs reduced (Scr), a homeotic gene of the Antennapedia complex encoding a homeodomain transcription factor.
Delete Scr and no salivary glands form; expand Scr expression and extra gland primordia appear along the body. One of its downstream targets is fork head (fkh), required for the gland secretory cells.
Decapentaplegic (Dpp), expressed dorsally, inhibits salivary gland formation nearby. Glands are therefore restricted to the ventral patch where Scr is on and Dpp is off. Without Dpp signaling, gland rudiments form all the way around the segment.
The heart is mesoderm-derived in all animals and is the first organ to function. The fly equivalent is the dorsal vessel.
The homeobox gene tinman is expressed in prospective heart mesoderm and is required for dorsal vessel formation — mutants have no dorsal vessel at all. GATA-family and T-box transcription factors are also needed, and vertebrates use similar gene families for heart specification: deep conservation of both structure and function.
Cardiac mesoderm is induced by an adjoining germ layer in both groups, but from different sides: in vertebrates the underlying anterior endoderm induces it; in Drosophila the overlying ectoderm does. Different signal source, same core transcription factors.
Insect tracheae form by branching morphogenesis — repeated branching of simple epithelial tubes into ever finer tubes. Loss of the Drosophila branchless gene, which encodes an FGF-family protein, wrecks the tracheal system.
Mechanism: mesenchymal cells near a tube tip secrete FGF; FGF binds its receptor on the epithelial cells; those cells proliferate and bud outward as a new tube. The mammalian homolog of branchless is required for the branching that builds the lung alveolar passageways.
Vertebrate organogenesis starts with two chordate-specific structures: the notochord and the hollow dorsal nerve cord. Building the nerve cord is neurulation. Watch Embryology | Neurulation, Vesiculation, Neural Crest Cell Migration on YouTube, from Ninja Nerd
The notochord is a flexible mesoderm-derived rod along the dorsal midline, appearing right after gastrulation. It supports the body of every chordate embryo; in vertebrates the vertebral column takes that job over later.
Neurulation: dorsal ectoderm above the notochord thickens into the neural plate as cells elongate; contracting actin bundles at the apical ends wedge the cells, rolling the plate into a neural groove; the groove edges (neural folds) meet and fuse into a hollow cylinder, the neural tube, which then pinches off from the surface ectoderm. Watch Embryology | Neurulation, Vesiculation, Neural Crest Cell Migration on YouTube, from Ninja Nerd
Hox gene complexes control the later regional differentiation of the neural tube into brain versus spinal cord regions. Watch Homeobox genes on YouTube, from Shomu's Biology
While the tube forms, mesoderm flanking the notochord organizes into rounded somitomeres, which then separate into segmented blocks called somites. Head mesoderm stays as unsegmented somitomeres and makes facial, jaw, and throat muscles.
Somites form in an anterior-to-posterior wave with measurable timing — about every 90 minutes in the chick. Cells at the presumptive boundary in the presomitic mesoderm signal the cells just anterior to condense. This segmentation clock runs on contact-mediated cell–cell signaling.
Somites are temporary. Their cells disperse and differentiate into skeleton, skeletal muscle, and dermis/connective tissue. Total number is species-specific: chickens make 50, some snakes up to 400.
Mesoderm lineages in birds and mammals: chorda-mesoderm → notochord; paraxial mesoderm → head mesoderm and somites (cartilage, skeletal muscle, dermis); intermediate mesoderm → kidneys and gonads; lateral plate mesoderm → circulatory system, body-cavity linings, extraembryonic tissues.
The most ventral mesoderm wraps around the endoderm and splits into two layers — one against the body wall, one against the gut. The space between them is the coelom, the adult body cavity.
As the neural groove closes, cells at the dorsal margin pinch off between the tube roof and the overlying ectoderm to form the neural crest, a migratory population. Watch Embryology of Nervous System - Neurulation - Neural Tube & Neural Crest - Embryonic Disc Folding on YouTube, from Medicosis Perfectionalis
Neurulation happens in all chordates, but only vertebrates make neural crest — it is considered a hallmark of vertebrate evolution. Watch Embryology of Nervous System - Neurulation - Neural Tube & Neural Crest - Embryonic Disc Folding on YouTube, from Medicosis Perfectionalis
Neural crest fate depends on the migratory pathway taken and the destination, not on prior determination. Transplantation shows cells from both cranial waves have identical potential.
Cranial neural crest moves anteriorly into the head and neck, contributing to skull and facial connective tissue and to peripheral nervous system neurons and glia. Shifts in where these cells end up drove the diversification of vertebrate heads. Watch Embryology of Nervous System - Neurulation - Neural Tube & Neural Crest - Embryonic Disc Folding on YouTube, from Medicosis Perfectionalis
Trunk neural crest, ventral pathway: cells pass through the anterior half of each adjoining somite, becoming sensory neurons of the dorsal root ganglia, Schwann cells, neurons of the autonomic ganglia, and endocrine cells of the adrenal medulla. That shared origin explains why epinephrine (adrenal hormone) and norepinephrine (sympathetic neurotransmitter) are chemically so similar. Watch Embryology of Nervous System - Neurulation - Neural Tube & Neural Crest - Embryonic Disc Folding on YouTube, from Medicosis Perfectionalis
Trunk neural crest, lateral pathway: cells travel just beneath the surface ectoderm all around the body and become skin pigment cells. Mutations hurting neural crest survival or migration produce ventral white spotting plus internal defects in other crest-derived tissues.
Molecular control of migration: prospective crest cells down-regulate N-cadherin to release from the neural tube, then display integrin receptors that let them grip extracellular matrix proteins along the route.
Evolutionary payoff: lancelets filter-feed with cilia driving water out through pharyngeal slits. Evolution converted those slits into the vertebrate gill chamber — cranial crest cells make the cartilage bars, induce nearby mesoderm to make the muscles, and supply the neurons connecting the CNS to those muscles. Better gas exchange allowed the shift from filter feeding to active predation.

52.5

Vertebrate Axis and Pattern Formation

pp. 1172–1178

Position within a germ layer largely decides what organ a cell will help build. In Drosophila, morphogen gradients set the axes; in vertebrates, Hox gene complexes work like fly homeotic genes to position organs along the anterior–posterior axis. Watch Homeobox genes on YouTube, from Shomu's Biology
The classic puzzle: how do dorsal ectoderm cells "know" they sit above the notochord and should become neural tube? Classic embryology solved it.
Spemann and Mangold transplanted dorsal lip of the blastopore cells from one amphibian gastrula to a ventral site on another. Some recipients grew a second complete set of dorsal axial structures — notochord, neural tube, somites — alongside their own, like conjoined twins. Watch Spemann-Mangold Organizer and embryonic induction on YouTube, from Zar
Using genetically distinguishable donors and hosts, they showed the induced notochord contained both host and donor cells. The transplanted cells acted as an organizer, recruiting cells that would have made belly skin to build dorsal structures instead. The belly cells already carried the genetic information; the organizer just switched it on.
An organizer is a cell cluster that releases diffusible morphogens, giving surrounding cells positional information. Distance from the organizer sets local concentration, and concentration sets fate. Watch Spemann-Mangold Organizer and embryonic induction on YouTube, from Zar
Induction can be shown with isolated blastula pieces: an animal cap alone makes only epidermis; a vegetal cap alone makes only endoderm; but animal cap + vegetal cap together makes the animal cap tissue form mesoderm. TGF-β family members — activin and Xenopus nodal-related proteins (Xnrs) — are the implicated inducers.
Origin of the organizer starts in the mother. Maternal dorsal determinants are deposited in the oocyte, with one accumulating at the vegetal pole of the unfertilized egg.
At fertilization, a signal from the sperm entry point triggers assembly of a parallel microtubule array that lets the plasma membrane and cortical cytoplasm rotate over the deeper cytoplasm — cortical rotation. This carries the dorsal determinant to the side opposite sperm entry, visible in some frogs as the gray crescent. Watch Spemann-Mangold Organizer and embryonic induction on YouTube, from Zar
Cells inheriting the shifted determinants during cleavage form the Nieuwkoop center, which changes its gene expression and becomes a signaling center. Its signals induce the overlying cells to become the dorsal lip — the Spemann–Mangold organizer.
The maternal dorsal determinants in Xenopus are thought to be mRNAs encoding Wnt-pathway proteins. Wnt signaling in the dorsal vegetal cells ultimately activates a transcription factor that enters the nucleus and turns on organizer genes.
The organizer works indirectly: instead of directly instructing dorsal fate, its molecules inhibit ventral development, so dorsal mesoderm appears by default.
All prospective frog mesoderm expresses BMP4. Cells with BMP4 receptors can become mesoderm, but how much BMP4 they bind sets which mesoderm — more BMP4 binding pushes toward more ventral fates.
The organizer secretes BMP4 antagonists that compete for the receptor. Up to 13 organizer proteins are known, most of them antagonists: Noggin, Chordin, Dickkopf, Cerberus. Noggin and BMP4 also shape finger and toe joints — humans homozygous for a Noggin mutation have fused joints.
Resulting gradient: cells farthest from the organizer bind the most BMP4 and become ventral mesoderm (blood, connective tissue); cells midway become intermediate mesoderm (kidneys, gonads); cells closest have BMP4 fully blocked and become the most dorsal mesoderm, somites. In ectoderm, blocking BMP4 produces neural tissue instead of epidermis.
In amniote vertebrates the organizer role belongs to Hensen's node at the anterior end of the primitive streak.
Pattern formation is the development and arrangement of anatomical structures in the correct relative position and 3D orientation. The chick limb bud is the classic model because all three axes show at once: anterior–posterior (digit 2 to digit 4), dorsal–ventral (back of hand to palm), and proximal–distal (shoulder to hand). Watch Apical Ectodermal Ridge, zone polarizing Activity Everything You Need To Know - Dr. Nabil Ebraheim on YouTube, from nabil ebraheim
AER (apical ectodermal ridge) sits at the limb bud tip and secretes FGF to drive outgrowth along the proximal–distal axis. Remove the AER early and the limb is severely truncated; remove it late and most of the limb forms, missing only the distal-most parts; add an extra AER and you get two limbs. FGF is needed continuously. Watch Apical Ectodermal Ridge, zone polarizing Activity Everything You Need To Know - Dr. Nabil Ebraheim on YouTube, from nabil ebraheim
The AER does not set limb identity — graft a forelimb AER onto a hindlimb site and you still get a hindlimb. Identity comes from Hox gene activity in the underlying mesenchyme, the progress zone.
ZPA (zone of polarizing activity) is mesenchyme that secretes sonic hedgehog (Shh). High Shh (close to the ZPA) makes posterior digits; as Shh falls with distance, more anterior digits form. Transplanting a second ZPA gives a mirror-image duplicate set of digits. Watch Apical Ectodermal Ridge, zone polarizing Activity Everything You Need To Know - Dr. Nabil Ebraheim on YouTube, from nabil ebraheim
Limb diversity comes from changes in gene regulation, not new genes. A bird wing and a human arm are both forelimbs and are homologous despite looking nothing alike.
Tbx5 is expressed in forelimb buds and Tbx4 in hindlimb buds, conserved in humans and birds. Human Tbx5 mutations cause Holt–Oram syndrome — combined forelimb and heart defects, fitting its descent from a heart gene.
Two rounds of whole-genome duplication early in vertebrate evolution turned the lancelet gene AmphiTbx4/5 (expressed in the amphioxus heart region) into Tbx4 and Tbx5.
Transgenic test: mice with the Tbx5 regulatory region driving the AmphiTbx4/5 coding region grow normal forelimbs; mice with the AmphiTbx4/5 regulatory region driving that same coding region grow no forelimbs. Conclusion: over ~520 million years the protein barely changed — what changed was the regulatory DNA.
Same story for digits: the two duplications gave four Hox clusters, including Hoxc and Hoxd. Normally only Hoxd affects digits (HOXD12 is in the forelimb, HOXC12 is not). Swap the upstream regulatory regions of Hoxc and Hoxd and HOXC12 becomes expressed in digits and partially rescues digit formation. New traits come from regulatory, not protein-coding, innovation.
Primary induction occurs between the three primary germ layers — for example dorsal ectoderm interacting with dorsal mesoderm during neurulation to make the neural tube.
Secondary induction occurs between tissues already committed to a pathway — the classic example is the eye lens.
Eye development by induction: the optic stalk grows out from the forebrain until it contacts surface ectoderm; that contact induces the ectoderm to invaginate and pinch off as a lens vesicle, which becomes the lens. The stalk forms the optic cup, which becomes the retina (sensory + pigment layers) and connects via the optic nerve. Lens cells then reciprocally induce the optic cup to form photoreceptors.
Spemann proved it: transplant a budding optic stalk beneath belly ectoderm and a lens forms there anyway, from cells that would have made abdominal skin.

52.6

Human Development

pp. 1178–1183

Human development from fertilization to birth averages 266 days (about 9 months), split into three trimesters. Watch Reproductive System, Part 4 - Pregnancy & Development: Crash Course Anatomy & Physiology #43 on YouTube, from CrashCourse
First cleavage occurs about 30 hours after fertilization; the second follows about 30 hours later.
By 6–7 days post-fertilization the embryo reaches the uterus as a blastocyst — ICM plus trophoblast. Trophoblast cells digest into the uterine endometrium during implantation, which completes at the end of week 1. The blastocyst then grows fast and begins forming the amnion and chorion. Watch Reproductive System, Part 4 - Pregnancy & Development: Crash Course Anatomy & Physiology #43 on YouTube, from CrashCourse
During week 2, the chorion and maternal endometrium combine to form the placenta, and gastrulation occurs.
In the placenta maternal and embryonic blood come very close but never mix. It exchanges gases, nourishes the embryo, detoxifies some molecules, and secretes hormones. It does not block alcohol, many drugs, or antibiotics — those pass straight to the embryo.
Placenta anatomy: the fetal component is the chorionic frondosum; the maternal component is the decidua basalis. Deoxygenated fetal blood arrives by the umbilical arteries; oxygenated blood returns by the umbilical vein.
Human chorionic gonadotropin (hCG) is secreted by trophoblast cells even before they become chorion. It is the hormone pregnancy tests detect. hCG maintains the corpus luteum, which keeps making estradiol and progesterone, preventing menstruation and further ovulation.
Week 3: neurulation occurs and the first somites appear, which will become muscles, vertebrae, and connective tissue. By the end of week 3 there are over a dozen somites, blood vessels and gut are starting, and the embryo is about 2 mm long. Watch Reproductive System, Part 4 - Pregnancy & Development: Crash Course Anatomy & Physiology #43 on YouTube, from CrashCourse Watch Embryology | Neurulation, Vesiculation, Neural Crest Cell Migration on YouTube, from Ninja Nerd
Week 4: organogenesis begins. Eyes form; the tubular heart develops four chambers and starts beating — about 70 beats per minute, roughly 2.5 billion beats over a 70-year life. Over 30 pairs of somites are visible, arm and leg buds appear, and the embryo is about 5 mm. Watch Reproductive System, Part 4 - Pregnancy & Development: Crash Course Anatomy & Physiology #43 on YouTube, from CrashCourse
Many women do not know they are pregnant at week 4, and most spontaneous miscarriages — usually from a defective embryo — happen during this period.
Second month: organogenesis continues. Limbs take adult shape (knees, elbows, fingers, toes), plus a short bony tail whose bones later fuse into the coccyx, an evolutionary vestige. Liver, pancreas, and gallbladder become evident. By month's end the embryo is about 25 mm long and weighs about 1 g.
The 9th week marks the transition from embryo to fetus — all major organs are established in their proper places. Watch Reproductive System, Part 4 - Pregnancy & Development: Crash Course Anatomy & Physiology #43 on YouTube, from CrashCourse
Third month: the nervous system develops; arms and legs move; facial expressions and primitive reflexes (startle, sucking) appear. Around week 10, placental hCG falls and the corpus luteum regresses, but menstruation still does not occur because the placenta itself now secretes estradiol and progesterone.
Those placental hormones suppress FSH and LH (blocking ovulation), maintain the uterus, prepare it for labor, and stimulate mammary gland development.
Second trimester (month 4 on): bones enlarge actively; by the end of month 4 the mother feels kicking. By the end of month 5 the fetal heartbeat is audible with a stethoscope (detectable by fetal monitor around week 10). Growth accelerates in month 6 — about 600 g and over 300 mm by its end, though the fetus still could not survive outside without major medical intervention.
Third trimester (months 7–9): organ growth and maturation, not new organ formation. Fetal weight doubles several times. Most major brain nerve tracts and many new neurons form now, yet neurological development is far from finished at birth. Watch Reproductive System, Part 4 - Pregnancy & Development: Crash Course Anatomy & Physiology #43 on YouTube, from CrashCourse
Why birth happens before the brain is finished: waiting would make the head too large to pass safely through the pelvis. Birth happens once survival probability is high, and the brain keeps adding neurons for months afterward.
Hormone curve across pregnancy: hCG rises sharply, peaks around month 2, then falls to near zero by about month 4. Estrogen and progesterone start rising around months 2–3 and climb steadily through month 9, with estrogen ending higher — the placenta has taken over.
Birth trigger: in some mammals the fetal adrenal cortex has an extra layer secreting corticosteroids that make the mother's uterus produce prostaglandins. In humans, rising fetal cortisol late in pregnancy appears to stimulate placental estradiol, which prompts prostaglandin release and increases uterine oxytocin receptors.
Labor sequence: prostaglandins start contractions → sensory feedback from the uterus triggers oxytocin release from the mother's posterior pituitary → oxytocin and prostaglandins together intensify contractions. This is positive feedback: contractions go from a few per hour to about one every 2–3 minutes. The expelled baby is a neonate.
Continued contractions then expel the placenta and membranes as the afterbirth. The umbilical cord is clamped and cut; clotting and cord muscle contraction stop the bleeding.
Lactation happens in mammary gland alveoli under the control of anterior-pituitary prolactin; milk travels through smooth-muscle-wrapped alveolar ducts to the nipple.
During pregnancy, high progesterone builds the alveoli and high estradiol builds the ducts — but estradiol also blocks prolactin action and suppresses prolactin secretion, so the gland is prepared but not producing. Placental human chorionic somatomammotropin and human somatotropin also drive mammary growth.
After birth, losing the placenta drops maternal estradiol and progesterone fast, releasing the block, so prolactin rises and milk production begins.
Milk let-down reflex: suckling sensory input → posterior-pituitary oxytocin → smooth muscle around the alveolar ducts contracts → milk ejected. That oxytocin also contracts the uterus, restoring uterine tone in breastfeeding mothers.
Colostrum is the yellowish first milk, rich in maternal antibodies; true milk synthesis begins about 3 days after birth. When nursing stops, accumulating milk signals the brain to stop prolactin.
Postnatal development runs for years — infants typically double birth weight in 2 months. Different organs grow at different rates and stop at different times, so infant proportions differ from adult ones (a newborn head is disproportionately large). That pattern is allometric growth.
Species contrast: in chimpanzees the brain and cerebral skull nearly stop growing at birth while the jaw keeps going, so adult and infant heads look very different. In humans brain, cerebral skull, and jaw keep growing at similar rates, so an adult head still resembles the infant one. Because human brain growth continues for years, nutrition and a safe environment in that window are critical.