2009 Lecture 6
This lecture will cover the early development of the ectoderm layer of the trilaminar embryo. Note that we will be returning to discuss neural (central nervous system; brain and spinal cord), neural crest (peripheral nervous system; sensory and sympathetic ganglia) and epidermis (skin contribution) development later in the current course.
- Understanding of events during the third and fourth week of development
- Understanding the process of notochord formation
- Understanding the process of early neural development
- Brief understanding of neural crest formation
- Brief understanding of epidermis formation
- Understanding of the adult components derived from ectoderm
- Brief understanding of early neural abnormalities
UNSW Embryology Links
- Human Embryology (3rd ed.) Chapter 5 p107-125
- The Developing Human: Clinically Oriented Embryology (6th ed.)
- Moore and Persaud Chapter 18 p451-489
- Essentials of Human Embryology Larson Chapter 5 p69-79
- Before We Are Born (5th ed.) Moore and Persaud Chapter 19 p423-458
UNSW Embryology Links
- Ectoderm Slides Neural Lecture 5 2008 | Neural Lecture 2008 - 1 slide/page | Neural 2008 Slides - 4 slides/page | Neural Lecture 2008 Slides - 6 slides/page
- Ectoderm Movies Notochord | File:Noto.jpgNotochord | File:Neuralplt.jpgNeural Plate | File:Neurul.jpgNeurulation | File:2neuro.jpgSecondary Neurulation
- Ectoderm Notes Neural Notes | Neural Crest Notes
The following text is extracted and modified from 2008 lecture slides and should be used as a "trigger" to remind you of key concepts.
- Early Neural Development (neuralation)
- axial process (mesoderm)
- notochordal plate
- neural plate
- neural groove
- neural tube
- Neural crest
- brain and spinal cord axes
- neural tube layers
- development of neurons and glia
The following text is extracted and modified from lecture slides and should be used as a "trigger" to remind you of key concepts.
Trilaminar Embryo: Neuralation begins at the trilaminar embryo with formation of the Notochord and somites, which underly the Ectoderm and do not contribute to the nervous system, but are involved with patterning its initial formation.
- forms initially as the Axial Process, a hollow tube which extends from the primitive pit , cranially to the oral membrane
- the axial process then allow transient communication between the amnion and the yolk sac through the neuroenteric canal.
- the axial process then merges with the Endodermal layer to form the Notochordal Plate.
- the notochordal plate then rises back into the Mesodermal layer as a solid column of cells which is the Notochord.
- 2 parts
- midline neural plate
- lateral surface ectoderm
- sensory placodes
- epidermis of skin, hair, glands, ant. pituitary, teeth enamel
- extends from buccopharyngeal membrane to primitive node
- forms above notochord and paraxial mesoderm
- neuroectodermal cells
- broad brain plate
- narrower spinal cord
- 3 components form: floor plate, neural plate, neural crest
Neural Determination- Neural Plate
- neuronal populations are specified before plate folds
- signals from notochord and mesoderm
- secrete noggin, chordin,follistatin
- all factors bind BMP-4 an inhibitor of neuralation
- bone morphogenic protein acts through membrane receptor Neural Determination- Neural populations
- neuronal populations are also specified before plate folds
- lateral inhibition generates at spinal cord level 3 strips of cells
- expression of delta inhibits nearby cells, which express notch receptor, from becoming neurons
- Delta-Notch- generates Neural strips Neural Groove
- forms in the midline of the neural plate (day 18-19)
- either side of which are the neural folds
- continues to deepen until about week 4
- neural folds begins to fuse
- at 4th somite level Neural Tube
- fusion of neural groove extends rostrally and caudally
- begins at the level of 4th somite
- "zips up" neural groove
- leaves 2 openings at either end- Neuropores
- forms the brain and spinal cord Secondary Neuralation
- caudal end of neural tube formed by secondary neuralation
- develops from primitive streak region
- solid cord canalized by extension of neural canal
- mesodermal caudal eminence Neuropores
- cranial neuropore closes before caudal
- failure to close- Neural Tube Defects (NTD)
- severity dependent upon level, spina bifida anancephaly (More? [../Notes/neuron2.htm Neural Abnormalities])
- found that supplementation of maternal diet with folate reduces incidence of NTDs
- A randomised controlled trial conducted by the Medical Research Council of the United Kingdom demonstrated a 72% reduction in risk of recurrence by periconceptional (ie before and after conception) folic acid supplementation (4mg daily).
- Women who have one infant with a neural tube defect have a significantly increased risk of recurrence (40-50 per thousand compared with 2 per thousand for all births) Neural Crest (More? [../Notes/ncrest.htm Notes Neural Crest])
- a population of cells at the edge of the neural plate that lie dorsally when the neural tube fuses
- dorsal to the neural tube, as a pair of streaks
- pluripotential, forms many different types of cells
- cells migrate throughout the embryo
- studied by quail-chick chimeras
- transplanted quail cells have obvious nucleoli compared with chicken Neural Crest Derivitives
- dorsal root ganglia
- autonomic ganglia
- adrenal medulla
- drg sheath cells, glia
- pia-arachnoid sheath
- skin melanocytes
- connective tissue of cardiac outflow
- thyroid parafollicular cells
- craniofacial skeleton
- teeth odontoblasts Early Brain Structure- 3 primary vesicles
- rostral neural tube forms 3 primary brain vesicles (week 4)
- prosencephalon (forebrain)
- mesencephalon (midbrain)
- rhombencephalon (hindbrain) Early Brain Structure- 5 secondary vesicles
- From the 3 primary vesicles developing to form 5 secondary vesicles
- telencephalon (endbrain, forms cerebral hemispheres)
- diencephalon (betweenbrain, forms optic outgrowth)
- rhombencephalon- metencephalon (behindbrain), myelencephalon (medullabrain) Ventricles (MH - this will be covered in late neural development)
- cavity within tube will form the contiguious space of the ventricules of the brain and central canal of spinal cord
- this space is filled initially with amniotic fluid, later with CerebroSpinal Fluid (CSF)
- CSF is secreted by a modified vascular structure, the [../Notes/neuron6.htm Chorioid Plexus], lying within the ventricles
- (More? [../Notes/neuron6.htm Notes Chorioid Plexus]) Brain Flexures
- rapid growth folds the neural tube forming 3 brain flexures
- cervical flexure - between brain stem and spinal cord
- midbrain flexure - pushes mesencephalon upwards
- pontine flexure - generates 4th ventricle Neural Layers
- neural stem cells lie in the layer closest to the ventricular space, the ventricular layer
- this layer generates both neuroblasts and glioblasts
- neuroblasts arise first and migrate along radial gial
- their migration stops at cortical plate Spinal Cord Axes
- Experimental manipulation of interactions.
- Initial experiments looked at how isolated tissues may influence the development of the spinal cord.
- Repositionining of specific tissues both in vivo and in vitro
- specific markers of or alteration of differentiation. Notocord Induction
- Ventral- Sonic Hedgehog
- notochord secretes sonic hedgehog
- Gene expression studies (ISH) showed shh gene expression occured in a subset of inducing tissues
- has a patterning role elsewhere (limb, sclerotome, lung)
- 2 signaling activities acting (locally and at a distance) Ventral- Sonic Hedgehog
- Binds to cell surface receptor patched
- without shh, patched (Ptc) binds smoothened (Smo)
- with shh shh-Ptc releases Smo activating G protein pathway Gene Diseases
- shh Human mutation- holoprosencephaly 3
- characteristic faces of the severe form of HPE which included a single fused eye (cyclopia) and a nose-like structure (proboscis) above the eye
- Downstream targets of Sonic hedgehog signalling:
- transcription factors like Gli3 (responsible for Greigs polycephalosyndactyly in humans)
- d Hoxd13 (responsible for polysyndactyly) Dorsal
- Dorsalin, growth factor controls patterning in embryonic mesoderm (frog)
- Transforming Growth factor beta, (TGF b), related factors BMP-2, BMP-4, BMP-7, radar (flies related protein determines dorsoventral)
- homology search of vertebrate library identified protein of same family.
- dorsalin-1 (dsl-1) (Basler, Cell 73, p687, 1993) Dorsalin-1
- From overlying ectoderm
- Naming comes from the obvious reason that it promotes the differentiation of neural crest cells.
- Also signal for dorsal signal of neural tube.
- Inhibits the differentiation of motoneurons.
- Implication is that dsl-1 and shh act antagonistically, or competitively to establish d-v axis of neural tube. Rostro-Caudal Axis
- What about the third pattern axis?
- Brain rostro-caudal axis is generated by differential expression of Hox genes (transcriptional activators)
- corresponding to genetic order on chromosome. (Wilkinson, Nature, 341, p405, 1989) Hox Genes
- Stands for Homeobox domain Genes
- A family of transcription factors
- Discovered in flies and conserved between all species. [../OtherEmb/fly.htm#antennapedia antennapedia]
- Expressed in sequence along the embryo rostro-caudal axis.
- Regulate many other aspects of development.
- 180aa region binds DNA and regulate gene expression
- large family of genes organized and expressed in sequence on the chromosome
- Nkx-2.2 first detected at 1 somite stage
- Lim hox gene expressed at spinal cord level Early Development and Neural Derivatives
- bilaminar embryo- hyoblast
- trilaminar embryo then ectoderm layer, neural plate, neural groove, neural tube and neural crest
- cranial expansion of neural tube- central nervous system
- caudal remainder of neural tube- spinal cord
- neural crest
- dorsal root ganglia
- parasympathetic / sympathetic ganglia.
- ectodermal placodes - components of the special senses: otic placode (otocyst), nasal placode, lens placode Neural tube and Genes: neural specification- Notch/Delta, patched receptor. Border- fibroblast growth factor (fgf), BMP (BMP4, msx1) Rostral border- Dlx5
Neural tube patterning
- segmented along its length- Hox/Lim gene expression
- ventral identity- sonic hedgehog, BMP7/chordin interaction
- dorsal identity- dorsalin
Human Neuralation - Early Stages
The stages below refer to specific Carneigie stages of development.
- stage 8 (about 18 postovulatory days) neural groove and folds are first seen
- stage 9 the three main divisions of the brain, which are not cerebral vesicles, can be distinguished while the neural groove is still completely open.
- stage 10 (two days later) neural folds begin to fuse near the junction between brain and spinal cord, when neural crest cells are arising mainly from the neural ectoderm
- stage 11 (about 24 days) the rostral (or cephalic) neuropore closes within a few hours; closure is bidirectional, it takes place from the dorsal and terminal lips and may occur in several areas simultaneously. The two lips, however, behave differently.
- stage 12 (about 26 days) The caudal neuropore takes a day to close
- the level of final closure is approximately at future somitic pair 31
- corresponds to the level of sacral vertebra 2
- stage 13 (4 weeks) the neural tube is normally completely closed
Secondary neurulation begins at stage 12
- is the differentiation of the caudal part of the neural tube from the caudal eminence (or end-bud) without the intermediate phase of a neural plate.
(Stage text modified from: Neurulation in the normal human embryo. O'Rahilly R, Muller F Ciba Found Symp 1994;181:70-82)
Critical Periods of Human Development to Teratogens
|The following links are to UNSW Embryology additional resources that provide further background information on the Lecture topics. Note that not all information found on these additional links is considered examinable and the lecture slides and laboratory classes should be used as your initial guide for course theory content.
Links: [../week/weekbyweek.htm#Week3 Timeline - Embryonic Week 3] | [../wwwhuman/Stages/Stages.htm Carnegie Stages] | [../Notes/neuron.htm Neural Notes] | [../Movies/neural.htm Neural Movies] | [../Defect/page5e.htm Folic Acid and Neural Tube Defects] | [../Notes/neuron2.htm Neural System - Abnormal Development] | [../Notes/ncrest.htm Neural Crest] | [../Notes/week3.htm Week 3] |
UNSW Embryology Links
Society for Neuroscience http://web.sfn.org/content/Publications/BrainFacts/index.html Brain Facts
Anatomy of the Human Body The Neural Groove and Tube
- Dr Mark Hill 2009 UNSW CRICOS Provider Code No. 00098G