Langman's Medical Embryology PDF

NOTES FROM LANGMAN’S MEDICAL EMBRYOLOGY  Genomic imprinting – only a gene inherited from the father or the mother is expressed PART 1 (page 1 to 140)...

NOTES FROM LANGMAN’S MEDICAL EMBRYOLOGY  Genomic imprinting – only a gene inherited from the father or the mother is expressed PART 1 (page 1 to 140) OTHER REGULATORS OF GENE EXPRESSION GENE TRANSCRIPTION  Nuclear RNA (nRNA) – initial transcript of a gene  Genes are contained in a chromatin o Sometimes called premessenger RNA o Chromatin = a complex of DNA and proteins o Longer than mRNA (histones) o Contains introns that are removed (spliced out) o Basic unit of structure = nucleosome  Alternative spicing – forms different proteins from the  Each nucleosome is made up of: same gene o an octamer of histone proteins o Spliceosomes – complexes that recognize specific o 140 base pairs of DNA splice sites o Joined together by linker DNA  Post-translational modifications o Keep DNA tightly coiled  HETEROCHROMATIN – chromatin that is inactive and INDUCTION AND ORGAN FORMATION coiled  INDUCTION – one group of cells or tissues causes o Cannot be transcribed another set of cells or tissues to change their fate; how  EUCHROMATIN – chromatin that is uncoiled organs form o Inducer – produces signal; initiates induction Gene Parts o Responder – to signal  Contain exons – contain DNA sequences that can be o Competence – capacity to respond to a signal translated into proteins)  requires activation of the responding  Contain introns (found in between exons; cannot be tissue by a competence factor translated into proteins)  Epithelial-mesenchymal interactions  Promoter region – this is where RNA polymerase binds  Crosstalk – between tissues or cells; needed for for the start of transcription differentiation to continue  Usually contains the sequence TATA (TATA box)  5’ CELL SIGNALING  Transcription initiation site  Needed for induction, competency to respond, and  Translation initiation site – to designate the first amino crosstalk acid in the protein  Paracrine interactions – involves diffusible proteins  Translation termination codon o Paracrine factors  3’ Poly A addition site – untranslated; has a sequence that o Growth and differentiation factors assists with stabilizing the mRNA  Juxtacrine interactions – no diffusible proteins involved o allows mRNA to exit the nucleus o allows mRNA to be translated into protein SIGNAL TRANSDUCTION PATHWAYS  Transcription termination site Paracrine Signaling Gene Transcription  Paracrine factors act by signal transduction pathways  DNA is transcribed from the 5’ to the 3’ end o ST Pathways – include a signaling molecule  Transcription factors (protein complex) are needed so that (ligand) and a receptor RNA polymerase can bind to the TATA box in the o Paracrine factors are important during promoter region development o Have a DNA-binding domain – specific to a  Receptor region of DNA o Has a ligand-binding region o Have a transactivating domain – binds to a o Transmembrane domain promoter or an enhancer; activates or inhibits the o Cytoplasmic domain gene  When a ligand binds its receptor, there’s a change that o Activate gene expression – causes DNA activates the cytoplasmic domain. This is to confer nucleosome complex to unwind enzymatic activity to the receptor.  Enhancers – regulatory parts of DNA o Kinase o Activate utilization of promoters to control o Phosphorylation efficiency and rate of transcription from the  Phosphorylation of proteins activates a transcription factor. promoter o Transcription factor activates or inhibits gene o Bind transcription factors through the expression. transcription factor’s transactivating domain o Silencers – enhancers that inhibit transcription Juxtacrine Signaling  Mediated through signal transduction pathways DNA Methylation Represses Transcription  Does not involve diffusible factors  DNA methylation of cytosine bases in the promoter  Occurs in three ways: regions represses gene transcription o A protein on one cell interacts with a receptor on  Genes in different types of cells (Ex. muscle cells make an adjacent cell muscle proteins but not blood proteins)  o Ligands in the extracellular matrix interact with o Limbs their receptors on neighboring cells. o Smooth muscle pattern o Direct transmission of signals from one cell to o Heart another by gap junctions o Gut  Important in tightly connected cells o Pharynx o Lungs Note: Ligands = GDFs o Pancreas o Kidneys Paracrine Signaling Factors - Regulate development and o Bladder differentiation of organ systems o Hair follicle  Four families: o Teeth 1. Fibroblast Growth Factor (FGF) o Thymocytes 2. WNT 3. Hedgehog o Inner ear 4. Transforming Growth Factor-Beta (TGF-Beta) o Eyes o Taste buds Fibroblast Growth Factors:  Sonic signaling –  Stimulate the growth of fibroblasts in culture o SHH protein binds to protein receptor Patched.  Can produce hundreds of protein isoforms by altering their When this happens, Patched stops inhibiting Smo, RNA splicing or their initiation codons and Smo is activated.  Important for angiogenesis, axon growth, and mesoderm  Patched inhibits the protein Smoothened differentiation (normally)  Activate FGFRs (fibroblast growth factor receptors) o When Smo is activated, it upregulates the activity  Responsible for specific developmental events (ex. devt. of of GLI. brain parts)  GLI – transcription factors that control target gene expression Hedgehog Proteins o SHH is cleaved after translation and cholesterol is  Code for a pattern of bristles on the leg that look like a added to it. This adding of cholesterol is what hedgehog links the SHH to the plasma membrane.  Sonic hedgehog – involved in many developmental events  Cholesterol is added to its N-terminal domain WNT Proteins o Dispatched (transmbembrane protein) releases  Involved in regulating limb patterning, midbrain SHH from the plasma membrane development, and somite and urogenital differentiation The Planar Cell Polarity: Convergent Extension Pathway TGF-Beta Superfamily  The PCP regulates the process of convergent extension  Important for forming extracellular matrix, epithelial  Convergent extension is a process in which a tissue branching, and bone formation becomes longer and narrower.  Regulates cell division, cell death (apoptosis), and cell o Ex. Elongation of neural plate to form neural migration groove  PCP – is the reorganization of cells and cell sheets in the Other Paracrine Signaling Molecules plane of a tissue (like what happens during convergent  Neurotransmitters – provide important signals for extension) embryological development  WNT pathway - Main PCP signaling pathway o Serotonin, GABA, epinephrine, norepinephrine o Includes Frizzled, Celsr, and Vangl o Act as ligands and bind to receptors like proteins do The Notch Pathway o Serotonin – cell proliferation and migration,  Notch receptors bind to ligands of the DSL (Delta-Serrate- establishing laterality, gastrulation, heart LAG-2) development  No second messengers involved here o Norepinephrine – apoptosis  Function: binding to a notch receptor results in cleavage of Notch protein KEY SIGNALING PATHWAYS FOR DEVELOPMENT  Notch protein then goes inside the nucleus and binds onto a DNA-binding protein. This stops the normal inhibiting of Sonic Hedgehog: Master Morphogen/Gene for Embryogenesis transcription of Notch proteins.  Morphogen – a molecule that establishes concentration  The Notch signaling is involved in: gradients and instructs cells on how to become different o Cell proliferation tissues and organs o Apoptosis  SHH (a protein) – involved in devt. of: o Epithelial to mesenchymal transitions o Vasculature  Notch is important in: o Axis formation o Neuronal differentiation o Midline o Blood vessel formation (angiogenesis) o Cerebellum o Somite segmentation o Neural patterning o Pancreatic beta-cell development  o B- and T- cell differentiation o Chromosomes start to condense, shorten, and o Devt. of inner ear hair cells thicken. o Septation of heart’s outflow tract o Chromosomes join together to form chromatids.  Alagille syndrome – cardiac outflow tract defects and Chromatids are joined together by centromeres. other abnormalities; caused by NOTCH mutation o However, the chromatids are not distinguishable yet here. Note: chromatid = one tube from the Note: Mesenchyme is a tissue found in organisms during chromosome development. It’s derived from the mesoderm.  PROMETAPHASE o Chromatids are distinguishable. CHAPTER 2—GAMETOGENESIS: CONVERSION OF GERM  METAPHASE CELLS INTO MALE AND FEMALE GAMETES o Chromosomes line up in the equatorial plane. o Centrioles have microtubules which attach to the PRIMORDIAL GERM CELLS centromeres of the chromosomes. – this  Fertilization is the process by which sperm (male gamete) microtubule set-up is called the mitotic spindle and oocyte (female gamete) unite to make a zygote.  ANAPHASE  Primordial germ cells – where gametes come from o Centromere of each chromosome divides.  During the second week of development, PGCs are formed o The chromatids go to the opposite ends of the in the epiblast spindle.  During the fourth week, PGCs start migrating to the yolk o Note: Individual chromatids are also referred to as sac to the developing gonads. chromosomes.  Dufring the fifth week, PGCs finally arrive at the gonads.  TELOPHASE  Gametogenesis – to prepare for fertilization, germ cells o Chromosomes uncoil and lengthen. have to go through this o Nuclear envelope forms again. o Includes meiosis o Cytoplasm divides (cytokinesis). o Includes cytodifferentiation  ENDING: o Each daughter cell gets the same number of CLINICAL CORRELATES chromosomes as the mother cell.  Terratomas – tumors of disputed origin that often contain a variety of tissues (ex. bone, hair, muscle, gut, etc) MEIOSIS  May arise from PGCs or from epiblast cells (Both of these  Happens in the GERM CELLS = spermatocytes and are pluripotent cells) primary oocytes  Tissues withn the tumors include derivatives from all three  Purpose: to make male and female gametes (sperm and germ layers oocyte)  Involves two cell divisions CHROMOSOME THEORY OF INHERITANCE o Why? Because one cell division = 46  Linked genes – genes on the same chromosome that are chromosomes. 2 cell divisions = 23 inherited together chromosomes.  Cells from all 46 chromosomes = diploid (mitosis) o To REDUCE the number of chromosomes to  Cells from 23 chromosomes = haploid (meisosis) haploid  In body cells (somatic), there are 23 homologous pairs of  Before meiosis, the GERM CELLS (M and F), replicate chromosomes. SO, somatic cells are haploid cells, because their DNA. 23 x 2 = 46 chromosomes.  Synapsis – two homologous chromosomes pair with each o Diploids = 46 chromosomes = somatic cells = other in a tetrad structure mitosis o Happens during Prophase 1 o Haploids = 23 chromosomes = sex cells = meiosis  Involves homologous chromosome pairing (SYNAPSIS)  Diploids: and CROSSOVER o 22 pairs of autosomes (matching chromosomes) o 1 pair of sex chromosomes Crossovers o for a total of 23 homologous pairs or 46  Happen in Meiosis 1 chromosomes  This is the interchange of chromatid segments between  Gametes: PAIRED homologous chromosomes o 1 chromosome of a pair = from oocyte (maternal  Allows recombination of genes between homologous gamete), 1 chromosome of a pair = from sperm chromosomes (paternal gamete)  Segments of chromatids break and are exchanged as the o Each gamete is a haploid = 23 chromosomes only homologous chromosomes separate  Chiasma (X-like structure) formation during separation MITOSIS  Enhances genetic variability  Each daughter cell gets 46 chromosomes. When a cell divides, the daughter cell still gets the same amount of Polar Bodies chromosomes.  In meiosis, ONE (1) primary oocyte makes four daughter  Before mitosis, a cell will go through DNA replication. cells. Each chromosome replicates its DNA. In this phase, o Each daughter cell has 22 autosomes and 1 X chromosomes are super long and are spread out. chromosome.  PROPHASE  o Only one of these will develop into a mature f. Incidence increases with age oocyte. i. 1 in 2000 – under 25 o The other three are the polar bodies and they will ii. 1 in 300 - 35 degenerate. iii. 1 in 100 – 40  In meiosis, ONE (1) primary spermatocyte makes four g. 4% unbalanced translocation daughter cells. h. 1% mosaicism from mitotic nondisjunction o Two have 22 autosomes + 1 X chromosome. o Two have 22 autosomes + 1 Y chromosome. 2. TRISOMY 18 o All four develop into mature spermatids. a. Intellectual disability b. Congenital heart defects c. Low-set ears Meiosis d. Flexion of fingers and hands Primary oocyte Primary spermatocyte e. Micrognathia Four daughter cells Four daughter cells f. Syndactyly Each has 22 + X chromosome Two have 22 + X chromosome g. Skeletal system malformation Two have 22 + Y chromosome h. 1 in 5,000 Only one will become a All become mature gametes i. High death rate – 1 year or less mature gamete (oocyte) (spermatids) Polar bodies will degenerate 3. TRISOMY 13 a. Intellectual disability CLINICAL CORRELATES b. Holoprosencephaly c. Congenital heart defects Birth Defects and Spontaneous Abortions: Chromosomal d. Deafness Abnormalities e. Cleft lip palate  Chromosomal abnormalities can be: f. Eye defects o NUMERICAL g. 1 in 20,000 o STRUCTURAL h. High death rate – 1 year or less  50% of spontaneous abortions have CAs  10% of birth defects are from CAs 4. Klinefelter Syndrome – 47 chromosomes; XXY  8% of birth defects are from gene mutations a. Sterility  A normal somatic cell is 2n (diploid). b. Testicular atrophy c. Gynecomastia (man boobs) NUMERICAL ABNORMALITIES d. Barr body  EUPLOID – any exact multiple of n; there is a change in the number of chromosomes by set 5. Turner Syndrome – 45, X o Ex. 1 extra chromosome per set a. Only monosomy that allows life o Triploidy – 3n b. Female in appearance o Tetraploidy – 4n c. No ovaries (gonadal dysgenesis) o Pentaploidy – 5n d. Short stature e. Webbed neck  ANEUPLOID – change in chromosome number by 1 f. Lymphedema (swelling of legs or arms) (usually 1 extra or 1 missing) g. Skeletal deformities o 2n + 1 = Trisomy = 47 chromosomes h. Widely spaced nipples o 2n – 1 = Monosomy = 45 chromosomes i. Nondisjunction in male gamete o 2n – 2 = Nulisomy o A result of nondisjunction – failure of chromatids 6. Triple X Syndrome – 47, XXX to separate during 1st or 2nd meiotic division a. Often undiagnosed  Mitotic nondisjunction – occurs during mitosis; produces b. Speech problem mosaicism c. Self-esteem problem o Mosaicism – some cells have abnormal numbers, d. Two sex chromatin bodies in cells while others don’t  Translocation – when pieces of one chromosome attach to STRUCTURAL ABNORMALITIES - caused by chromosome another breakage o Balanced – no genetic material is lost; normal 1. Cri Du Chat – partial deletion in Chromosome 5 person a. Cat-like cry o Unbalanced – part of one chromosome is lost b. Small head (microcephaly) c. Intellectual disability NUMERICAL ABNORMALITIES d. Congenital Heart Disease 1. DOWN SYNDROME (TRISOMY 21) 2. Angelman Syndrome – microdeletion on maternal a. Extra copy of Chromosome 21 chromosome b. Flat, broad face; protruding tongue a. Intellectual disability c. Intellectual disability b. No speech d. Broad hand with a simian crease c. Poor motor devt. e. Caused by meiotic nondisjunction (most of the time) d. Laughter i. During oocyte formation 3. Prader-Willi Syndrome – microdeletion on paternal chromosome  a. Hypotonia  Meiosis II is only completed if the oocyte is fertilized— b. Obesity if not, then the cell degenerates 24 hours after c. Intellectual disability ovulation. d. Hypogonadism e. Testes that don’t drop into place (undescended SPERMATOGENESIS – all the events by which spermatogonia testes) are transformed into spermatozoa 4. Fragile X Syndrome  PGCs stay dormant until puberty a. Intellectual disability  PGCs differentiate into spermatogonia at puberty. b. Large ears  Primary spermatocytes – undergo two successive meiotic c. Prominent jaw divisions  to produce 4 spermatids d. Large testes  Spermatids go through spermiogenesis (a series of changes) GENE MUTATIONS o Acrosome formed  Single gene mutation – one gene is affected only o Nucleus condensed  Dominant mutation o Neck, middle, tail formed  Recessive mutation o Cytoplasm (most) shed  Inborn errors of metabolism  A spermatogonium takes 74 days to become a mature spermatozoon MORPHOLOGICAL CHANGES DURING MATURATION OF THE GAMETES CHAPTER 3—FIRST WEEK OF DEVELOPMENT:  Oogenesis – process whereby oogonia differentiate into OVULATION TO IMPLANTATION mature oocytes; process by which the female gametes are created OVARIAN CYCLE  With each ovarian cycle, a lot of primary follicles start 1) Maturation of oocytes begins before birth (so, formation of growing, but only one becomes fully mature. primary oocytes begins before birth):  Thus, only one oocyte is released at ovulation.  Once a primordial germ cell (PGC) gets to the ovary of a  During ovulation, the oocyte is in METAPHASE of female, it differentiates into oogonia. Meiosis II. o PGC undergoes mitotic division  Oogonium o Surrounded by zona pellucida and granulosa cells  Oogonia undergo mitotic division (series of them)   What carries the oocyte into the uterine tube is the primary oocytes in prophase sweeping action of the tubal fimbriae.  Each primary oocyte is surrounded by primordial follicle. FERTILIZATION Note: Oogonia = immature female sex cell; Primary oocyte =  Before spermatozoa can fertilize the oocyte, they must go mature female sex cell through a process:  All of a female’s oogonia will be created while she is still 1. Capacitation a fetus. The surviving oogonia will enter meiosis 1 and a. A glycoprotein coat and seminal plasma become primary oocytes. proteins are removed from the sperm head  After primary oocytes replicate their DNA, they stay in 2. Acrosome Reaction prophase 1 of meiosis near birth. They stay in prophase a. Acrosin- and trypsin-like substances are 1 until the menstruation cycle begins 10-13 years after released birth. b. Acrosin- and trypsin-like substances  Then, for 30-45 years, every month, primary oocytes penetrate the zona pellucida resume meiosis where they left off and complete Meiosis 1.  The sperm (spermatozoon) MUST penetrate: 1. Corona Radiata 2) Maturation of oocytes continues at puberty 2. Zona Pellucida  Diplotene Stage – a resting stage during prophase; oocytes 3. Oocyte Cell Membrane stay here until puberty  Oocyte maturation inhibitor  As soon as the spermatocyte has entered the oocyte:  600k-800k primary oocytes at birth 1. The oocyte finishes Meiosis II. It forms the FEMALE  Antral stage – vesicular/antral follicle PRONUCLEUS.  Mature vesicular stage – mature vesicular (graafian) 2. The ZONA PELLUCIDA becomes impenetrable to follicle other spermatozoa. o Theca interna – secretes steroids, rich in blood 3. The sperm’s head separates from the tail and swells. It vessels forms the MALE PRONUCLEUS. o Theca externa – merges with ovary’s CT  In every ovarian cycle, only one follicle reaches full  The MALE AND FEMALE PRONUCLEI replicate their maturity. The others become atretic. DNA.  Luteinizing hormone - induces preovulatory growth phase  Afterwards, paternal and maternal chromosomes mingle  Meiosis I completes and forms 2 daughter cells – one is a and split longitudinally. secondary oocyte, the other is a polar body  They then go through mitotic division, giving rise to the TWO-CELL STAGE.   Results of Fertilization: a. Cortical and Zona Reactions 1. Diploid number of chromosomes is restored (half from b. Resumption of the 2nd Meiotic Division mom and half from dad) c. Metabolic Activation of the Egg 2. Chromosomal sex is determined 4. What are the primary causes of infertility in men and women? 3. Cleavage is initiated a. Male – not enough sperm; poor motility b. Female – occluded uterine tubes; hostile cervical CLINICAL CORRELATES mucus; immunity to spermatozoa; absence of  Infertility – a problem for 15% to 30% of couples ovulation  Assisted Reproductive Technology (ART) – solution to infertility CHAPTER 4—SECOND WEEK OF DEVELOPMENT:  In Vitro Fertilization (IVF) – involves fertilizing eggs in BILAMINAR GERM DISC a culture and then putting them in the uterus at the 8 th-cell stage Day 8  Intracytoplasmic Sperm Injection (ICSI) – a single  At the start of the second week, the blastocyst is partially sperm is injected into an egg’s cytoplasm embedded in the endometrial stroma.  Cons:  The trophoblast differentiates into: o Higher risk for birth defects, prematurity, low o Cytotrophoblast - an inner, actively reproducing birth weight, and multiple births layer o Syncytiotrophoblast – an outer layer, erodes maternal tissues CLEAVAGE  A series of mitotic divisions that results in an increase in blastomeres. Day 9 o With each mitotic division, the blastomeres get  Lacunae develop in the syncytiotrophoblast (outer layer) smaller.  After three mitotic divisions, blastomeres undergo Days 11 and 12 compaction. They become a tightly grouped ball of cells  By this time, the blastocyst is completely embedded in the with inner and outer layers. endomaterial stroma.  Maternal sinusinoids are eroded by the BLASTOCYST FORMATION syncytiotrophoblast.  Compacted blastomeres divide to form a 16-cell morula.  Maternal blood enters the lacunar network.  The morula enters the uterus on the third or fourth day after fertilization. During this time, a cavity starts to Day 13 appear, and the blastocyst forms.  By this time, a primitive uteroplacental circulation begins.  Inner cell mass – will develop into the embryo proper  The cytotrophoblast, meanwhile, forms primary villi  Outer cell mass - will form the trophoblast (columns) that penetrate into the syncytium.  Inner cell mass (embryoblast) differentiates into: UTERUS AT TIME OF IMPLANTATION o Epiblast  During this time, the uterus is in a secretory phase. o Hypoblast o Uterine glands and arteries become coiled. o Together they form a bilaminar disc  The blastocyst implants in the endometrium along the  Epiblast cells – give rise to amnioblasts anterior or posterior wall.  Hypoblast cells – surround the primitive yolk sac  If fertilization doesn’t happen, then the menstrual phase  By the end of 2nd week, extraembryonic mesoderm fills the begins. space between the trophoblast and the amnion and  Three layers in the endometrium: exocoelomic membrane. o Compact layer – sheds during menstruation o The extraembronic coelom/chorionic cavity forms o Spongy layer – sheds during menstruation when vacuoles develop in this tissue. o Basal layer – the only part that is retained;  Extraembryonic somatic mesoderm – extraembryonic regenerates other layers during the next cycle mesoderm lining the cytotrophoblast and amnion  Extraembryonic splanchnic mesoderm – lining 1. What is corpus luteum? Role and origin? surrounding the yolk sac a. A corpus luteum is a mass of cells that forms in an ovary. The 2nd week of development is known as the week of 2’s: b. It forms from the empty follicle left behind after 1. Trophoblast differentiates into two layers: ovulation. a. Cytotrophoblast c. It is responsible for producing progesterone during b. Synctiotrophoblast early pregnancy. It is also involved in ovulation and 2. The embryoblast forms two layers: regulation of menstrual cycle. a. Epiblast 2. What are the three phases of fertilization? b. Hypoblast a. PHASE 1: Penetration of the corona radiate 3. The extraembryonic mesoderm splits into two layers: b. PHASE 2: Penetration of the zona pellucida a. Somatic layer c. PHASE 3: Fusion of the oocyte and sperm cell b. Splanchnic Layer membranes 4. Two cavities form: 3. What actions occur during Phase 3 (fusion of the membranes)? a. Amniotic cavity  b. Yolk sac cavity  This process continues to produce germ layers for more caudal areas of the embryo until the end of the 4th week. CLINICAL CORRELATES  Tissue and organ differentiation has begun.  Implantation happens at the end of first week. o It happens in a cephalocaudal direction.  Trophoblast cells invade the epithelium and endometrial o Gastrulation continues. stroma with the help of proteolytic enzymes.  Implantation can happen outside the uterus (ectopic FURTHER DEVELOPMENT OF THE TROPHOBLAST pregnancies)  Primary villi get a mesenchymal core in which small capillaries arise. CHAPTER 5: THIRD WEEK OF DEVELOPMENT-  When these villous capillaries make contact with TRIMALINAR GERM DISC capillaries in the chorionic plate and connecting stalk: o The villous system is ready to supply the embryo GASTRULATION: FORMATION OF EMBRYONIC with its nutrients and oxygen. MESODERM AND ENDODERM  The major event that happens during the 3rd week CHAPTER 6—THIRD TO EIGHTH WEEKS: THE EMBRYONIC  It begins with a primitive streak appearance. PERIOD o At the cephalic end there is a primitive node.  The embryonic period (3rd to 8th weeks) is the period  In the part with the node and streak, epiblast cells move during which each of the 3 germ layers gives rise to its inward to form new cell layers: own tissues and organ systems. o Endoderm  Because organs are formed, major features of body form o Mesoderm are established.  Cells that don’t move through the streak but stay in the epiblast form: DERIVATIVES OF THE ECTODERMAL GERM LAYER o Ectoderm  This germ layer rise to the organs and structures that  So, EPIBLAST cells give rise to all three germ layers maintain contact with the outside world: (Endoderm, Mesoderm, Ectoderm): 1. CNS o These form all of the tissues and organs 2. PNS 3. Sensory epithelium of EAR, NOSE, and EYE FORMATION OF THE NOTOCHORD 4. Skin (including hair and nails)  Prenotochordal cells move forward until they reach the 5. Pituitary, Mammary, and Sweat Glands prechordal plate. 6. Enamel of the teeth  They intercalate in the endoderm as the notochordal  Induction of the neural plate is regulated by the plate. inactivation of BMP4 (a growth factor).  After more development, the plate detaches from the o Cranial region – inactivation is caused by Noggin, endoderm – and the NOTOCHORD is formed. Chordin, and Follistatin  The notochord forms a midline axis, which will serve as o Hindbrain and Spinal Cord region – inactivation the basis of the axial skeleton. is caused by WNT3a and FGF  Cephalic and caudal ends of the embryo are established before the primitive streak is formed. DERIVATIVES OF THE MESODERMAL GERM LAYER  Paraxial Mesoderm ESTABLISHMENT OF THE BODY AXES  Intermediate Mesoderm  Cells in the hypoblast (endoderm) at the cephalic end form  Lateral Plate Mesoderm the AVE (anterior visceral endoderm)  Paraxial mesoderm forms somitomeres o The AVE– expresses head-forming genes (OTX2,  Somitomeres give rise to mesenchyme of the head, which LIM1, HESX1) is organized into somites.  NODAL – involved in initiating and maintaining the  Somites give rise to: integrity of the node and streak o Myotome – muscle tissue  With FGF present, BMP4 ventralizes mesoderm during  Epimere gastrulation so that it forms intermediate and lateral plate  Hypomere mesoderm. o Sclerotome – cartilage and bone  Chordin, noggin, and follistatin antagonize BMP4 activity. o Dermatome – dermis They dorsalize mesoderm to form the notochord and  Once SHH is secreted by the notochord and floor plate of somitomeres in the head region. neural tube – it induces the sclerotome. FATE MAP ESTABLISHED DURING GASTRULATION DERIVATIVES OF THE ENDODERMAL GERM LAYER  Epiblast cells moving through the node and streak are  Epithelial lining of the: predetermined by their position to become specific types o GI Tract of mesoderm and endoderm. o Respiratory Tract o Urinary Bladder GROWTH OF THE EMBRYONIC DISC o Tympanic Cavity  By the end of the third week, three basic germ layers o Auditory Tube (ectoderm, mesoderm, and endoderm) are established in  Parenchyma of the: the head region. o Thyroid o Parathyroids  o Liver o Ventral Mesentery – exists only in part of the o Pancreas esophagus, the stomach, and the upper part of the duodenum PATTERNING OF THE ANTEROPOSTERIOR AXIS: REGULATION BY HOMEOBOX GENES DIAPHRAGM AND THORACIC CAVITY  Four clusters: HOXA, HOXB, HOXC, HOXD—on four  Diaphragm – divides the body cavity into: chromosomes o Thoracic Cavity  Genes at the 3’ end – control development of cranial o Peritoneal Cavity structures  Thoracic Cavity is divided into (by the pleuropericardial  Genes at the 5’ end – control development of posterior membranes): structures o Pericardial Cavity  Hindbrain and embryonic axis patterning is controlled o Pleural Cavities (2) EXTERNAL APPEARANCE DURING THE SECOND MONTH FORMATION OF THE DIAPHRAGM  Embryonic disc begins to get longer and to form head and  Diaphragm - develops from four components: tail regions. This causes the embryo to curve into the fetal 1. Septum Transversum (Central Tendon) position. 2. Pleuroperitoneal Membranes  The embryo also forms two lateral body wall folds that 3. Dorsal Mesentery of the Esophagus grow ventrally and close the ventral body wall. 4. Muscular Components from Somites at C3-C5 o This causes the amnion to be pulled ventrally – a. C3, C4, and C5 keep the diaphragm alive and the embryo to lie within the amniotic cavity.  Connection with the yolk sac and placenta is maintained CHAPTER 8—THIRD MONTH TO BIRTH: THE FETUS AND through: PLACENTA o Vitelline duct o Umbilical cord DEVELOPMENT OF THE FETUS  Extends from 9th week of gestation until birth  Characterized by rapid growth of the body and maturation of organ systems CHAPTER 7: THE GUT TUBE AND THE BODY CAVITIES  3rd, 4th, and 5th months – 5cm of growth per month  last 2 months – 700 g of weight gain per month A TUBE ON TOP OF A TUBE  6 to 9 lb at birth  At the end of the third week, the neural tube is elevating o