DEVELOPMENT OF THE VERTEBRATE BODY PLAN Thomas A. Marino, Ph.D. Temple University SChool of MediCine DEVELOPMENT OF THE VERTEBRATE BODY PLAN Early Development 1. Development of ECtoderm A. Neural Tube B. Surface ECtoderm 2. Development of Endoderm A. G.I. Tract B. Respiratory Tree C. Pharynx 3. Development of Mesoderm A. Paraxial B. Intermediate Summary of Week 2 Trophoblast Cytotrophoblast SynCyQotrophoblast Embryonic Ectoderm Embryonic Mesoderm Embryonic Epiblast Mesoderm ExtraembryoniC BlastoCyst mesoderm PrimiQve Streak NotoChordal Process Epiblast Notochord Embryonic Endoderm Amnioblasts Inner Cell Mass Hypoblast ExtraembryoniC Yolk Sac endoderm Endoderm Trilaminar Embryo So by day 18 of gestation, gastrulation is nearing completion and the trilaminar Ectoderm mesoderm embryo will begin: 1.Neurulation 2.Lateral body folding 3.Head and tail folding ! The trilaminar embryo has three layers: Notochord 1.Ectoderm 2.Mesoderm 3.Endoderm Endoderm Trilaminar Embryo As the third week of gestation is coming to an end, the mesoderm layer paraxial mesodermparaxial mesoderm begins to subdivide into three masses: 1.Paraxial mesoderm 1. This will become the somites. 2.Intermediate mesoderm. 1. This will give rise to much of the urogenital system. 2.Lateral plate mesoderm. 1. This will become 1. Lateral plate splanchnic mesoderm intermediate mesoderm 2. Lateral plate somatic mesoderm lateral mesoderm Ectoderm Neurulation begins with the notochord cells migrating around the primitive node. Notochord Neural Plate Ectoderm As the notochord cells migrate in a cephalic direction, the overlying ectoderm cells will begin Notochord to differentiate into neural ectoderm or the neural plate. Neural Plate Ectoderm Oral Plate The notochord and the neural PreChordal plate cells will grow cephalically. Plate 1.This growth will stop in the region of the prechordal plate. 2.Cephalic to the prechordal Notochord plate is the oral plate. 1. The oral plate is ectoderm and Neural endoderm without Plate intervening mesoderm. 2. The oral plate demarcates the separation between the prospective oral cavity and the developing gut tube. Neurula'on – how does neural ectoderm develop? ! •BMP gradients lead to formaQon of intermediate and lateral Chordin mesoderm. Noggin ! Follistatin •Chordin, Noggin and FollistaQn ! form in Cranial paraxial ! mesoderm. They bind to and ! inacQvate BMP. FGF ! WNT3a •They are present in notoChord and paraxial mesoderm and induce eCtoderm to beCome neural plate. ! •WNT3a and FGF do this in the Caudal paraxial mesoderm. ! •Without BMP inacQvaQon the epidermal phenotype is Neural crest forma'on Neural Crest Cells form in response to ! Chordin ! Noggin Follistatin Intermediate levels of BMP ! ! ! ! BMP ! This leads to PAX3 expression FGF + WNT3a FOXD3 expression is neCessary for neural Crest formaQon And SLUG expression allows for to neural Crest migraQon Bone morphogene'c protein signalling and vertebrate nervous system development Aimin Liu & Lee A. Niswander Nature Reviews Neuroscience 6, 945-954 (December 2005) The CNS arises from a speCialized epithelium, the neural plate (1). This proCess relies on the inhibiQon of bone morphogeneQC protein (BMP) signaling. Folding of the neural plate to produCe the neural groove is triggered by the formaQon of a disQnCt hinge point in the ventral region (the floor plate; 2). At the end of neurulaQon, the lateral edges of the neural plate fuse (3) and segregate from the non- neural epithelium to form a neural tube (4). The roof plate and floor plate form at the dorsal and ventral midline of the neural tube, respeCQvely. The roof plate beComes a new organizing Centre that produCes BMPs, whiCh provide dorsal paaerning informaQon. Neural Crest Cells derive from the dorsal neural tube and migrate out to form the PNS, as well as melanoCytes and CarQlage in the head. Neural Crest Cells have been shown to form at an intermediate level of BMP signaling. Ectoderm The next stage of Neural neurulaQon in the Groove formaQon of the Neural neural tube. The Plate lateral edges of the neural plate will form neural folds and a midline neural groove appears. Fig. 1 (A) Successive images showing the progression of neural tube closure in a stylized vertebrate embryo (rostral = up). J B Wallingford et al. Science 2013;339:1222002 Published by AAAS Fig. 3 Multiple cell behaviors contribute to neural tube morphogenesis. Multiple cell behaviors contribute to neural tube morphogenesis. In this schematic, pink and green cells illustrate convergent extension. By exchanging neighbors specifically in the mediolateral (horizontal) axis, the sheet of cells is elongated in the anteroposterior (vertical) axis. Blue cells illustrate apical constriction. These cells do not move but rather change their shape, leading to a bend in the tissue sheet. [Schematic adapted from (7)] J B Wallingford et al. Science 2013;339:1222002 Published by AAAS Ectoderm As the third week Comes to Neural Groove Neural Fold an end the Somites neural folds beCome prominent and they approach one another in the CerviCal region. Day 20 Ectoderm The neural tube is PeriCardial first formed in the Bulge CerviCal region. It then ConQnues to Somites form in a CephaliC and Caudal direCon. Neural Tube Ectoderm The last two areas to fuse are the Cranial Neuropore Cranial neuropore PeriCardial Bulge CephaliCally and the Caudal neuropore Caudally. Somites Caudal Neuropore UNSW Embryology This link takes you to the University of New South Wales embryology website where you Can see an image of an embryo at 22 days of gestaQon. NeurulaQon is nearly Complete. Lateral Body Folding • As neurulaQon oCCurs the embryo begins lateral body folding. Lateral Body Folding • Lateral body folding involves: – The eCtoderm at either end meeQng in the ventral midline. – The endoderm forming the gut tube. Lateral Body Folding • The lateral plate mesoderm will split into somaQC and splanChniC mesoderm. • In between the two the body Cavity will form. • This space on both sides will also fuse in the midline. Body cavity Somatic mesoderm Splanchnic mesoderm Lateral Body Folding • As the space between the lateral plate somaQC and splanChniC mesoderm enlarges the lateral body folding connues. Body cavity 23 Lateral Body Folding Body cavity Amniotic Cavity Gut Tube • The amnioQC Cavity will also fold around the embryo. Lateral Body Folding • The two ends of the eCtoderm, lateral plate somaQC mesoderm, lateral plate splanChniC mesoderm and the endoderm ConQnue to migrate ventrally. Lateral Body Folding • The amnioQC Cavity and the body Cavity also migrate ventrally. Lateral Body Folding • Now the amniotic cavity surround the embryo which is surrounded by ectoderm. • The fused body cavities are surrounded by lateral plate somatic mesoderm deep to the ectoderm • The lateral plate splanchnic mesoderm surround the gut tube which is a fused tube of endoderm Somatic mesoderm Splanchnic mesoderm Body Gut Tube cavity Lateral Body Folding Paraxial mesoderm Intemediate Surface eCtoderm mesoderm Neural Tube AmnioQc Cavity Body Gut Tube Cavity Chorionic Cavity The embryo is surrounded by the chorionic cavity which surrounds the amniotic cavity. Lateral Body Folding This is a very niCe animaQon of lateral body folding that will give you a beaer three dimensional sense of the proCess. However this require the flash plugin. UNSW Embryology • This is an image from the UNSW embryology website. It shows a 23 – 26 day old embryo (week 6 LMP). The neural tube is fusing with embryo is undergoing lateral body folding. • Another image Can be see by CliCking here. Surface ECtoderm Neural epidermis, hair, nails, Crest: cutaneous and mammary glands, anterior pituitary gland, cranial and sensory ganglia enamel of teeth, inner ear, and and nerves, lens medulla of adrenal gland, pigment cells, branchial arch cartilages, head mesenchyme mesoderm Ectoderm Neural Tube central nervous system, retina, pineal body, posterior pituitary Endoderm Ectoderm then develops into three main categories: surface ectoderm, neural crest derivatives and neural tube derivatives. Endoderm • ConQnuing the disCussion of lateral body folding and adding head and tail folding The development of the endoderm Can be Considered as it develops into: – Pharynx – GI tract – Respiratory system – Caudal urogenital system struCtures Endoderm Aer: – Lateral Body Folding – Head and Tail Folding The endoderm Consists of: – Foregut – Midgut – Hindgut Endoderm If a sagittal section of the embryo is made and looked at from the side one can see the ectoderm (blue), mesoderm (red) and endoderm (yellow). Endoderm • Dorsal to the ectoderm is the amniotic cavity and ventral to the endoderm is the yolk sac. • The chorionic cavity surrounds these structures. • The connecting stalk connects the embryo to the placenta. • The cephalic end of the embryo is defined by the oral plate. Connecting stalk Oral plate Amniotic Cavity Yolk Sac Chorionic Cavity Endoderm • The cephalic end of the embryo grows the fastest and as it does the brain moves into a cephalic position and move the oral plate ventrally and caudally. • This leaves two cul-de-sacs at either end of the gut tube called the foregut and hindgut. foregut hindgut brain Oral plate Endoderm The gut tube begins at the oral plate, starts as the foregut, continues as the midgut which is still continuous with the yolk sac and then becomes the hindgut ending as the cloacal plate. foregut hindgut midgut Cloacal Plate Oral Plate Allantois Heart Yolk Sac ENDODERM Cloaca Allantois A diverticulum from the connecting stalk called