Early Development I & II Lecture Notes PDF

L22 & L23 Early Development Dr. Erin Stephenson email: [email protected] Learning objectives Define the three major stages of prenatal development Define gametogenesis Describe the process of fertilization Describe the process of cleavage Describe h...

L22 & L23 Early Development Dr. Erin Stephenson email: [email protected] Learning objectives Define the three major stages of prenatal development Define gametogenesis Describe the process of fertilization Describe the process of cleavage Describe how a blastocyst is formed Describe the process of implantation Describe how a bilaminar embryonic disc forms and identify any associated structures/cavities Identify the extraembryonic membranes observed during week two and describe how each forms Discuss the process of gastrulation List the three primary germ layers and describe the major structures derived from each layer Describe the structures formed during neurulation Identify the structures formed during intraembryonic mesoderm differentiation Describe the structures formed during embryonic folding Describe the period of embryonic development when an embryo is most susceptible to teratogens Lecture outline Stages of prenatal development Gametogenesis Pre-embryonic period Week 1 Week 2 Early embryonic period Teratogens  Key terminology Conceptus = developing human Primordial = earliest stage of development Blast = embryonic cell Cyto = cell Cyst = bladder (fluid-filled sac) Epi = above Hypo = below Endo = inner Extra = outside Intra = within Meso = middle Ecto = outer Coelom = cavity Lecture outline Stages of prenatal development Gametogenesis Pre-embryonic period Week 1 Week 2 Early embryonic period Week 3 Week 4 Teratogens Learning objective(s): Define the three major stages of prenatal development Stages of prenatal Pre-embryonic Weeks 1-2 development Three key periods  Pre-embryonic  Embryonic  Fetal Embryonic Most visible development occurs Weeks 3-8 during the embryonic period Fetal Weeks 9-38 Lecture outline Stages of prenatal development Gametogenesis Pre-embryonic period Week 1 Week 2 Early embryonic period Week 3 Week 4 Teratogens Learning objective(s): Discuss the key stages of gametogenesis  Gametogenesis DNA condenses into chromosomes Duplicated sister chromatids unite at centromere & undergo recombination Chromosomes align at  Gametogenesis = germ cells → gametes equator  Meiosis Anaphase I Gametes = sex cells capable of reproduction  Male = sperms/spermatozoa  Female = oocytes Telophase I & cytokinesis Chromosome number is halved  46 (diploid) → 23 sister chromatids → 23 (haploid)  Requires two meiotic divisions Diploid = cells have two closely similar versions of each chromosome Sister chromatids = twin copies of replicated chromosomes that are physically linked Homologs = versions of chromosomes that are similar but not identical Haploid = cells have one version of each chromosome  Spermatogenesis Spermatogonia → primary spermatocytes  Occurs during puberty  Diploid germ cells First meiotic division  Two haploid secondary spermatocytes Second meiotic division  Four haploid spermatids Spermatids → sperms via spermiogenesis  Spermatids elongate & mature into sperms  Oogenesis Prior to birth Ovulation Oogonia → Primary oocytes Oocyte begins second meiotic  Occurs prior to birth division then arrests Puberty  Diploid cell surrounded by a follicular layer First meiotic division  Begins prior to birth – arrests at prophase Fertilization  Completed monthly beginning at puberty  One secondary oocyte, one polar body Second meiotic division Just before ovulation  Begins at ovulation – arrests at metaphase  Complete upon penetration by a sperm  One fertilized oocyte, one polar body  Ovarian cycle No fertilization? Begins at puberty, terminates at menopause Hypothalamus stimulates release of gonadotropins from the pituitary gland  Follicle stimulating hormone (FSH)  Stimulates follicular maturation  Luteinizing hormone (LH)  Stimulates production of estrogens  More estrogen = more LH = ovulation Ovulation  Follicle becomes corpus luteum  Secretes estrogen & progesterone  Endometrium of uterus thickens Lecture outline Stages of prenatal development Gametogenesis Pre-embryonic period Week 1 Week 2 Early embryonic period Week Learning 3 objective(s): Weeksthe Describe 4-8 process of fertilization Teratogens Describe the process of cleavage Describe how a blastocyst is formed Describe the process of implantation  Pre-embryonic period Ovarian Cycle Week 1  Fertilization  Cleavage  Blastocyst formation  Implantation Week 2  Bilaminar disc forms  Lacunae form  Extraembryonic mesoderm develops  hCG secretion begins Week 1 Blastocyst Fertilization Cleavage formation Implantation  Fertilization Union of genetic material Begins when a capacitated sperm penetrates a secondary oocyte  Secondary oocyte completes second meiosis Pronuclei of ovum & sperm combine Formation of a diploid zygote 46 chromosomes  Cleavage Repeated mitotic divisions of the zygote Increases the number of blastomeres Results in formation of a morula  12-32 blastomeres in a solid mass Begins ~30 h after fertilization as the zygote moves along the uterine tube  Blastocyst formation Development of a fluid-filled cavity within the morula  Pushes the inner-cell mass to one side The blastomere divides into two structures –  Inner cell mass/embryoblast  Trophoblast Begins ~4 d after fertilization  Implantation Blastocyst embeds in the uterine endometrium Begins ~6 d & continues into Week 2 The trophoblast differentiates into two layers  Cytotrophoblast Day 6  Syncytiotrophoblast The syncytiotrophoblast erodes the uterine tissues to facilitate implantation Day 12 Day 7  Summary of Week 1 Cleavage Zygote formation Blastocyst formation Implantation Lecture outline Stages of prenatal development Gametogenesis Pre-embryonic period Week 1 Week 2 Early embryonic period Week 3 Learning objective(s): Weeks 4-8 Describe the process of implantation Teratogens Describe how a bilaminar embryonic disc forms and identify any associated structures/cavities Identify the extraembryonic membranes observed during week two and describe how each forms Week 2 Bilaminar embryonic disc & Extraembryonic cavities Lacunae mesoderm Implantation continues “Week of twos”  Bilaminar embryonic disc Embryoblast changes morphology during implantation  Forms a bilaminar disc Epiblast  Dorsal surface Hypoblast  Ventral surface Day 8 Bilaminar embryonic disc  Amnionic cavity ~ Week 7, 17 mm embryo Forms within the epiblast Amnioblasts separate from the epiblast & surround the amniotic cavity  Amnion Will eventually surround the conceptus Day 8  Primary umbilical vesicle Cells continuous with the hypoblast line the cytotrophoblast, forming a vesicle  Primary umbilical/exocoelomic vesicle/yolk sac Day 8  Lacunar network Syncytiotrophoblast erodes uterine blood vessels  Lacunae Lacunar network allows diffusion of nutrients/gasses via maternal blood Day 9 Extraembryonic mesoderm Extraembryonic mesoderm Cells migrate between the exocoelomic membrane & cytotrophoblast  Extraembryonic mesoderm Spaces form & coalesce  Future chorionic cavity/gestational sac Day 12 Extraembryonic mesoderm Extraembryonic somatic mesoderm  Lines the trophoblast & amnion  Forms the connecting stalk – primitive umbilical cord  Fuses with the trophoblast to form the chorion Extraembryonic splanchnic mesoderm  Surrounds the primary umbilical vesical Day 14 Prechordal plate Localized thickening of the hypoblast Organizing center for structures of the head from which the oropharyngeal membrane will arise Day 14  Future mouth Human chorionic gonadotropin (hCG) Produced by the syncytiotrophoblast at the end of Week 2 Maintains the corpus luteum of the ovary  Progesterone, estrogen Summary of Week 2 Implantation continues The embryoblast differentiates into a bilaminar embryonic disc  Epiblast & hypoblast The amniotic cavity appears in the epiblast The primary umbilical vesicle & extraembryonic mesoderm develop Lacunar networks & chorionic villi form The extraembryonic coelom forms from spaces that develop in the extraembryonic mesoderm  Future chorionic cavity The primary umbilical vesicle becomes smaller & gradually disappears  Secondary umbilical vesicle develops The prechordal plate develops as a localized thickening of the hypoblast The syncytiotrophoblast begins secreting hCG Lecture outline Stages of prenatal development Gametogenesis Pre-embryonic period Week 1 Week 2 L23: Early Development II Early embryonic period Week 3 Week 4 Learning objective(s): Teratogens Discuss the process of gastrulation List the three primary germ layers and describe the major structures derived from each layer Describe the structures formed during neurulation Identify the structures formed during intraembryonic mesoderm differentiation Embryonic period Early embryonic period Week 3 Differentiation of intraembryonic Gastrulation Neurulation mesoderm Gastrulation Bilaminar disc → trilaminar disc  Primary germ layers Establishment of body plan Cranial – caudal axis Left – right sides Begins with appearance of primitive streak Primitive streak Epiblast cells migrate to median plane Primitive node appears  Marks cranial side of primitive streak  Streak elongates caudal → cranial Invagination of cells creates primitive groove  Trilaminar disc Mesenchymal cells migrate through the primitive streak  Epiblast converted to ECTODERM  Epithelial tissues Cells that displace/replace the hypoblast  Forms the ENDODERM  Epithelial tissues Cells that migrate between the ectoderm & endoderm  Intraembryonic MESODERM  Mesenchymal or epithelial tissues  Notochord formation Migrating mesenchymal cells form the notochord process  Cellular cord between primitive node & prechordal plate  Binds underlying endoderm  Fused layers degenerate leaving the notochord plate Notochord plate folds inward to form the notochord  Signaling hub  Forms longitudinal axis of axial skeleton Notochord formation in 3 mouse embryos Foxa2-eGFP and T-mCherry are fluorescent proteins that mark the paraxial mesoderm Credit: HHMI News  Neurulation Notochord signaling induces the neural plate  Thickening of overlying ectoderm – neuroectoderm The neural plate invaginates  Forms the neural groove & neural folds Neural folds meet in the midline  Forms the neural tube  Future central nervous system  Formation of the neural plate Ectoderm overlying the notochord begins to thicken Formation of the neural groove Invagination of the neural plate begins Formation of the neural folds Invagination of the neural plate continues Deepening of the neural groove & formation of neural crest cells Neural folds migrate toward one another whereas neural crest cells migrate away from the developing neural tube Closure of the neural tube Neural folds unite in the midline & the tube closes  Closure of the neural tube Begins in cervical region & occurs bidirectionally Complete by end of Week 4 Incomplete closure is problematic  Cranial end – anencephaly (lethal)  Caudal end – spina bifida (loss of function) Link to video  Neural crest cells Undergo epithelial → mesenchymal transition Migrate away from the neural folds  Separate into right & left divisions  Widely distributed along predefined pathways  Form ganglia, Schwann cells, pharyngeal arches & their derivatives, leptomeninges, melanocytes, odontoblasts, suprarenal medulla  Ectoderm summary Ectoderm is derived from the epiblast Neuroectoderm is a thickened region over the notochord that becomes the neural tube & neural crest Surface ectoderm becomes the epidermis  Intraembryonic mesoderm Germ layer between the ectoderm & endoderm Derived from the epiblast Differentiates into three parallel columns  Paraxial mesoderm  Intermediate mesoderm  Lateral plate mesoderm Anterior Posterior Link to video cells cells migrate to migrating paraxial laterally mesoderm Mesoderm differentiation in a chick embryo. Sweetman D, Wagstaff L, Cooper O, Weijer C & Münsterberg A. (2008). The migration of paraxial and lateral plate mesoderm cells emerging from the late primitive streak is controlled by different Wnt signals. BMC Dev. Biol. , 8, 63. PMID: 18541012 DOI.  Paraxial mesoderm Paired columns either side of the notochord Columns condense & segment into somites ~Day 22, 2.5 mm  38-39 somites develop craniocaudally from days 26-32  Form the sclerotome, myotome, & dermatome  Vertebrae, ribs, posterior skull  Skeletal muscles of the limbs & trunk  Skin over the back & limbs ~Day 23, 3.0 mm ~Day 24, 3.5 mm  Intermediate mesoderm Continuous laterally with the paraxial mesoderm Precursor to parts of the urinary & reproductive systems  Kidneys & ureters  Gonads, reproductive ducts, glands  Uterus  Lateral plate mesoderm Continuous laterally with the extraembryonic mesoderm  Covers the umbilical vesicle & amnion Divides into somatic (parietal) & splanchnic (visceral) layers Transverse folding fuses right & left sides in the midline  Intraembryonic coelom – future thoracic & abdominopelvic cavities Mesoderm summary Mesoderm is derived from the epiblast Paraxial mesoderm Somites Intermediate mesoderm Urogenital structures Lateral plate mesoderm Somatic (parietal) mesoderm Splanchnic (visceral) mesoderm  Endoderm Germ layer surrounding the umbilical vesicle Derived from the epiblast Will form the lining of the gut tube  Most internal organs will bud from the gut tube Foregut – oropharyngeal membrane Midgut – secondary umbilical vesicle Hindgut – cloacal membrane  Oropharyngeal & cloacal membranes Sites where ectoderm fuses directly with endoderm Oropharyngeal membrane is at the cranial end  Future mouth  Foregut Cloacal membrane is at the caudal end  Future anal & urogenital openings  Hind gut Summary of germ layer derivatives Lecture outline Stages of prenatal development Gametogenesis Pre-embryonic period Week 1 Week 2 Early embryonic period Week 3 Week 4 Learning Teratogens objective(s): Describe the structures formed during embryonic folding Week 4 Embryonic Neural tube closure folding  Embryonic folding Conversion of elongating disc into curved cylinder Caused by differential growth along longitudinal axis & lateral parts of disc Craniocaudal folding & transverse folding occur simultaneously  Craniocaudal folding Caused by rapid growth of the neural tube Oropharyngeal & cloacal membranes move to ventral surface Endoderm of umbilical vesicle is internalized  Foregut, midgut, hind gut established Link to video  Transverse folding Caused by rapid growth of the somites Bilateral edges of conceptus fuse in the midline Gut tube formed as splanchnic mesoderm & endoderm fuse Body wall formed as somatic mesoderm & surface ectoderm fuse  Except at the vitelline duct (stalk of umbilical vesicle) Summary of Weeks 3 & 4 Gastrulation establishes body planes & generates the primary germ layers from the epiblast  Ectoderm, mesoderm, endoderm The notochord is established as a signaling hub that initiates neurulation Neurulation establishes the nervous system & neural crest cells The intraembryonic mesoderm differentiates into three paired columns  Paraxial, intermediate, lateral plate The endoderm forms the lining of the gut tube The oropharyngeal & cloacal membranes are established The conceptus converts from disc to tube via folding in the craniocaudal & transverse axes  Craniocaudal folding internalizes future thoracoabdominal structures  Transverse folding forms the gut tube, body wall, & surrounds the conceptus with the amnionic cavity Lecture outline Stages of prenatal development Gametogenesis Pre-embryonic period Week 1 Week 2 Early embryonic period Week 3 Week 4 Teratogens Learning objective(s): Describe the period of embryonic development when an embryo is most susceptible to teratogens  Teratogens Most deaths during infancy are caused by birth defects  Genetic factors, environmental factors, a combination Teratogens are substances/organisms/physical agents that can interfere with normal development  Slowed growth, loss of function, malformations, death Learning objectives  We defined the three major stages of prenatal development  We discussed the process of gametogenesis  We described the process of fertilization  We described the process of cleavage  We described how a blastocyst is formed  We described the process of implantation  We described how a bilaminar embryonic disc forms and identified the associated structures/cavities  We identified the extraembryonic membranes observed during week two and described how each forms  We discussed the process of gastrulation  We identified the three primary germ layers & described the major structures derived from each  We described the structures formed during neurulation  We identified the structures formed during intraembryonic mesoderm differentiation  We described the structures formed during embryonic folding  We described the period of embryonic development when an embryo is most susceptible to teratogens Links to summary videos Gastrulation https://youtu.be/ADlYn0ImTNg Neurulation https://youtu.be/lGLexQR9xGs Folding https://youtu.be/yXUv4MPuNTA