BMS 150 Embryology Neurulation, Folding, and Development of the Nervous System PDF

Embryology Neurulation, Folding, and Development of the Nervous System Reference – Chapters 4 & 5 BMS 150 The Developing Human, 8th ed. Week 8 Moore, Persaud, & Torchia Cell and tissue lineages  Week 3 – The Notochord Roles of the notochord: 1. Establishes...

Embryology Neurulation, Folding, and Development of the Nervous System Reference – Chapters 4 & 5 BMS 150 The Developing Human, 8th ed. Week 8 Moore, Persaud, & Torchia Cell and tissue lineages  Week 3 – The Notochord Roles of the notochord: 1. Establishes the longitudinal axis of the embryo and gives it some rigidity 2. Provides signals for the development of axial MSK structures and the CNS 3. Contributes to the intervertebral discs  Week 3 – The Notochord Development of the notochord: mesenchymal cells dive into the primitive pit and migrate cephalad ▪ they form a cord called the notochordal process ▪ The notochordal process develops a lumen known as the notochordal canal ▪ Pictures correspond to days 16, 17, and 18 Week 3 – The Notochord After the notochordal process approaches the prechordal plate, the floor of the process “fuses” with the endoderm ▪ The notochordal process is now the notochordal plate ▪ The amniotic cavity and the umbilical vesicle can communicate through an opening (the neurenteric canal) – this opening is where the primitive pit opened into the notochordal canal At this point, the notochordal plate cells proliferate and fold inwards, forming the fully-developed notochord ▪ No canal is present ▪ Notochordal plate ! notochord transition starts cranially and progresses caudally After the notochord is fully-developed, the neurenteric canal is obliterated Transformation of the notochordal process ! notochordal plate Middle of 3rd week Note the neurenteric canal, lack of endoderm in the floor of the plate Transformation of the notochordal plate ! notochord Middle of 3rd week Neural groove and different mesodermal regions visible, the notochord has no canal, and endoderm is present between the notochord and the umbilical vesicle The prechordal plate and notochord as organizers The notochord and its preceding structures (process, plate) are important organizers ▪ induce the overlying ectoderm to develop into the neural plate ▪ The notochord also serves as the central axis of the embryo – the divider between right and left ▪ The signaling mechanisms responsible for this induction are complex and will not be explored here The notochord structures approach the prechordal plate, but do not go beyond it ▪ As mentioned previously, the prechordal plate is an important organizer for development of cranial structures ▪ Also the “stop signal” preventing the notochord from developing too far anteriorly  Oropharyngeal and Cloacal Membranes The prechordal plate develops into the oropharyngeal membrane ▪ Two-layer membrane – ectoderm and endoderm, no mesoderm ▪ Cardiogenic mesoderm found anteriorly The cloacal membrane forms caudal to the primitive streak ▪ Also two layers – ectoderm and endoderm, no mesoderm ▪ Future site of the anus Allantois Small, vascularized diverticulum (outpouching) from the caudal wall of umbilical vesicle, extending into connecting stalk Functions in early blood formation and bladder development ▪ Blood vessels become umbilical arteries ▪ Small portion persists as urachus that extends from bladder to umbilical region Becomes median umbilical ligament in adults Day 18 Neurulation Notochord induces overlying ectoderm to form the neural plate ▪ Known as neuroectoderm ▪ Gives rise to the CNS, retina, and the tissues that arise from the neural crest ▪ Neuroectodermal cells are very tall and columnar in shape ▪ As the organism matures, the neural plate extends beyond the notochord On day 18, the neural plate invaginates to form the neural groove – neural folds are found on either side of the groove The neural folds eventually fuse together, and form the neural tube ▪ The neural tube is the primordium of the CNS Neurulation Neurulation is therefore the process by which the neural tube is formed Begins with neural plate formation Ends when the tube becomes completely “closed” – no opening at either the caudal or cephalic ends Weeks ▪ Neurulation is 3-4 complete at the end of the 4th week ▪ Note the location of the neural crest cells Neural Crest Cells Subset of neuroectodermal cells Originate from the “crest” at the apex of the neural folds Lose affinity to epithelium and Weeks neighbouring cells 3-4 Migrate dorso-laterally on either side of the tube Many migrate widely throughout the mesenchyme  Neural Crest Cells Derivatives of the neural crest include: ▪ Ganglia of CN V, VII, IX, X ▪ Spinal ganglia (i.e. dorsal root ganglia) ▪ Autonomic nervous system ganglia ▪ Neurolemma sheaths of peripheral nerves ▪ Contribute to the arachnoid and pia ▪ Adrenal medulla ▪ Melanocytes ▪ Craniofacial bone and cartilage ▪ Portions of the heart Intraembryonic Mesoderm During the 3rd week: ▪ Intraembryonic mesoderm proliferates to form a thick column of mesoderm on either side of the notochord Beside the axis of the organism (as defined by the notochord) = paraxial mesoderm ▪ The intermediate mesoderm is found just lateral to the paraxial mesoderm ▪ The lateral mesoderm is lateral to the intermediate mesoderm Somites During the 3rd – 5th week, somites develop adjacent to the neural tube Somite = cuboidal masses of mesoderm on either side of the notochord, visible along the dorso-lateral surface of the embryo on each side of the neural tube Formed from the paraxial mesoderm Somites give rise to most of the axial skeleton and associated musculature, as well as the dermis in those areas Intraembryonic Mesoderm During the 3rd week mesenchymal cells migrate anteriorly, lateral to the notochordal process to eventually form cardiogenic mesoderm ▪ Found anterior to the prechordal plate, eventually gives rise to the embryonic heart primordia ▪ The heart begins as a pair of tubes that are brought together by folding of the embryo (see later) Top – day 16, early in development of notochordal process Bottom – day 20 – heart primordium cephalad to the prechordal plate Intraembryonic Coelom The primordium of the intraembryonic coelom (embryonic body cavity) appears as isolated spaces in the lateral mesoderm and cardiogenic mesoderm ▪ These spaces soon coalesce (join together) and form a single horseshoe-shaped intraembryonic coelom Intra-embryonic coelom divides the lateral mesoderm into two layers: ▪ A somatic or parietal layer of lateral mesoderm located beneath the ectodermal epithelium and continuous with the extraembryonic mesoderm covering the amnion ▪ of lateral mesoderm next to the endoderm and continuA splanchnic or visceral layer ous with the extraembryonic mesoderm covering the umbilical vesicle Intraembryonic Coelom Note the horseshoe- shape of the intraembryonic coelom By about day 21 the coelomic spaces have formed a continuous cavity Intraembryonic Coelom Three general structures can be Day 19 seen in the region of the lateral mesoderm: ▪ Somatopleure – the somatic mesoderm and the overlying ectoderm Day Forms the body wall 20 ▪ Splanchnopleure – the splanchnic mesoderm and the underlying intraembryonic endoderm Forms the embryonic gut ▪ Intraembryonic coelom in Day between the somatopleure and 21 splanchnopleure Intraembryoni c Coelom During the 2nd month, the intraembryonic coelom develops into 3 main body cavities: ▪ Pericardial cavity ▪ Pleural cavity ▪ Peritoneal cavity Week 3 - Summary The bilaminar embryonic disc is converted into a trilaminar embryonic disc during gastrulation. These changes begin with the appearance of the primitive streak, which appears at the beginning of the third week as a thickening of the epiblast at the caudal end of the embryonic disc. The primitive streak results from migration of epiblastic cells to the median plane of the disc. Invagination of epiblastic cells from the primitive streak gives rise to mesenchymal cells that migrate ventrally, laterally, and cranially between the epiblast and hypoblast. As soon as the primitive streak begins to produce mesenchymal cells, the epiblast is known as embryonic ectoderm. Some cells of the epiblast displace the hypoblast and form embryonic endoderm. Mesenchymal cells produced by the primitive streak soon organize into a third germ layer, the intraembryonic or embryonic mesoderm, occupying the area between the former hypoblast and cells in the epiblast. Cells of the mesoderm migrate to the edges of the embryonic disc, where they join the extraembryonic mesoderm covering the amnion and umbilical vesicle. Early in the third week, mesenchymal cells from the primitive streak form the notochordal process between the embryonic ectoderm and endoderm. The notochordal process extends from the primitive node to the prechordal plate. Openings develop in the floor of the notochordal canal and soon coalesce, leaving a notochordal plate. This plate infolds to form the notochord, the primordial axis of the embryo around which the axial skeleton forms (e.g., vertebral column). Week 3 - Summary At the end of the third week, the embryo is a flat ovoid embryonic disc. Mesoderm exists between the ectoderm and endoderm of the disc everywhere except at the oropharyngeal membrane, in the median plane occupied by the notochord, and at the cloacal membrane. The neural plate appears as a thickening of the embryonic ectoderm, induced by the developing notochord. A longitudinal neural groove develops in the neural plate, which is flanked by neural folds. Fusion of the folds forms the neural tube, the primordium of the CNS. As the neural folds fuse to form the neural tube, neuroectodermal cells form a neural crest between the surface ectoderm and neural tube. The mesoderm on each side of the notochord condenses to form longitudinal columns of paraxial mesoderm, which, by the end of the third week, give rise to somites. The coelom (cavity) within the embryo arises as isolated spaces in the lateral mesoderm and cardiogenic mesoderm. The coelomic vesicles subsequently coalesce to form a single, horseshoe-shaped cavity that eventually gives rise to the body cavities. Blood vessels first appear in the wall of the umbilical vesicle (yolk sac), allantois, and chorion. They develop within the embryo shortly thereafter. Fetal and adult erythrocytes develop from different hematopoietic precursors – more to be discussed later The primordial heart is represented by paired endocardial heart tubes. By the end of the third week, the heart tubes have fused to form a tubular heart that is joined to vessels in the embryo, umbilical vesicle, chorion, and connecting stalk to form a primordial cardiovascular system – more to be discussed later  Embryonic Folding Embryonic folding is the process by which a relatively “flat” embryonic disk becomes more and more cylindrical in shape Folding occurs in two general planes ▪ The median plane – the anterior and posterior ends of the embryo move ventrally. Also known as cranial-caudal folding ▪ The horizontal plane – the lateral edges of the embryonic disk move ventrally. Also known as lateral folding The edges “roll” ventrally towards the umbilical vesicle Embryonic Folding Folding begins at the end of the 3rd week and is easy to see in the 4th week ▪ As it folds cranially, the brain vesicles first begin to appear, and a few somites are obvious ▪ As it folds laterally, the body wall is formed  Day 21 Day 22 Day 25 Day 28 Cranial Folding – Key Aspects Part of the endoderm of the umbilical vesicle is incorporated into the embryo as the foregut ▪ The foregut lies between the brain and heart ▪ Oropharyngeal membrane separates the foregut from the stomodeum ▪ Stomodeum = the primordium of the mouth Cranial Folding – Key Aspects Septum transversum lies caudal to the heart ▪ develops into the central tendon of the diaphragm and separates the abdominal cavity from the thoracic cavity Cranial Folding – Key Aspects The position of the heart changes due to the head fold: ▪ Heart moves to the ventral surface of the embryo ▪ pericardial coelom lies ventral to the heart and cranial to the septum transversum  Tail Folding – Key Aspects As the embryo grows, the caudal eminence (tail region) projects over the cloacal membrane (future site of anus) Part of the endodermal germ layer is incorporated into the embryo as the hindgut The connecting stalk (primordium of umbilical cord) is now attached to the ventral surface of the embryo, and the allantois is partially incorporated into the embryo  Lateral Folding – Key Aspects Lateral folding is caused by the rapidly growing spinal cord and somites As the abdominal walls form, part of the endoderm germ layer is incorporated into the embryo as the midgut Initially, there is a wide connection between the midgut and umbilical vesicle after lateral folding, the connection is reduced to an omphaloenteric duct ▪ The region of attachment of the amnion to the ventral surface of the embryo is also reduced to a relatively narrow umbilical region Germ Layer Derivatives - Overview  Germ Layer Derivatives The three germ layers (ectoderm, mesoderm, and endoderm) formed during gastrulation give rise to the primordia of all the tissues and organs Ectoderm: Mesoderm: Endoderm: CNS, PNS; sensory connective tissue; epithelial lining of the epithelia of the eyes, cartilage; bone digestive and respiratory ears, and nose striated and smooth tracts, parenchyma of the epidermis and its muscles; heart, blood, and tonsils appendages (hair and lymphatic vessels; kidneys; thyroid and parathyroid nails); mammary glands; ovaries; testes; genital glands, thymus subcutaneous glands; ducts; serous membranes liver, and pancreas, enamel of teeth; lining the body cavities epithelial lining of the pituitary gland (pericardial, pleural, and urinary bladder and most Neural crest cells – peritoneal); spleen; and of the urethra discussed previously cortex of suprarenal epithelial lining of the glands tympanic cavity, tympanic antrum, and eustachian tube  Development of the Nervous System - Overview The events of neurulation have already been discussed ▪ Neural plate can be seen at day 19 ▪ Neural plate ! neural groove ! neural tube ▪ Conclusion of neurulation with the closure of the neuropores (day 27) – at this point the neural tube no longer communicates with the amniotic cavity After neuropore closure, a basic blood circulation has been established (covered later) At day 22, the cranial 2/3 of the neural tube forms the brain, caudal 1/3 of the neural tube will form the spinal cord ▪ The neural folds fuse at the level of the 5th somite, proceeds cranially and caudally  Spinal Cord Development The lateral walls of the caudal portion of the neural tube thicken until only the tiny central canal remains Ventricular zone is the first layer to develop – gives rise to all neurons and macroglia Eventually the neural tube develops into an inner ventricular zone, a medial intermediate zone, and an outer marginal zone ▪ The intermediate zone becomes populated with primordial neuroblasts derived from the ventricular zone ▪ The outer marginal zone develops into white matter tracts  Spinal Cord Development When the neuroepithelial cells cease producing neuroblasts and glioblasts, they differentiate into ependymal cells ▪ ependymal cells line the central canal of the spinal cord The alar and basal plates of the developing spinal cord are separated by a groove – the sulcus limitans ▪ Plates are formed by sites of rapid growth of the neuroepithelium Cell bodies in the alar plates form the dorsal gray horns ▪ Neurons in these horns constitute afferent, or sensory, nuclei; groups of these nuclei form the dorsal gray horns Cell bodies in the basal plates form the ventral and lateral gray horns ▪ Axons of ventral horn cells grow out of the spinal cord and form the ventral roots of the spinal nerves – these have a predominantly motor function The unipolar neurons in the spinal ganglia (dorsal root ganglia) are derived from neural crest cells ▪ These grow axons and synapse with the nuclei in the dorsal horns or travel up through the white matter to the brain (usually both) Mesenchyme surrounding the spinal cord forms the meninges Spinal Cord Development Neural Crest Cell Derivatives - the PNS Neuro- epithelium Derivatives Brain Development - Overview Fusion of the neural folds in the cranial region and closure of the rostral (anterior) neuropore form three primary brain vesicles: ▪ Forebrain (prosencephalon) ▪ Midbrain (mesencephalon) ▪ Hindbrain (rhombenceophalon) During week 5, the prosencephalon partially divides into two secondary brain vesicles ▪ Telencephalon and diencephalon By week 5, the rhombencephalon also partially divides ▪ Metencephalon and myelencephalon Brain Development - Overview Forebrain Week 5 Development As closure of the rostral (anterior) neuropore occurs (day 25), two lateral outgrowths-optic vesicles- appear one on each side of the forebrain ▪ primordia of the retinae and optic nerves A second pair of diverticula, the telencephalic vesicles, arise more dorsally and rostrally ▪ They are the primordia of the cerebral hemispheres, and their cavities become the lateral ventricles Three swellings develop in the lateral walls of the third ventricle, which later become the thalamus, hypothalamus, and the epithalamus Week 7 – sagittal section