2009 Lecture 6

Ectoderm Development

== Introduction ==

This lecture will cover the early development of the ectoderm layer of the trilaminar embryo. Note that we will be returning later to discuss neural (central nervous system; brain and spinal cord) and neural crest (peripheral nervous system; sensory and sympathetic ganglia). Epidermis (integumentary, skin contribution) development will be briefly mentioned due to its ectoderm origin, but will also be covered later in the current course.

Lecture Objectives

• 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

Textbook References

• Human Embryology (3rd ed.) Chapter 5 p107-125
• The Developing Human: Clinically Oriented Embryology (6th ed.)

Other textbooks

• 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 | Notochord | Neural Plate | Neurulation | Secondary Neurulation
• Ectoderm Notes Neural Notes | Neural Crest Notes | Neural Abnormalities | Integumentary Development

Lecture Summary

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)
• Mesoderm - axial process (mesoderm), notochordal plate, notochord
• Ectoderm - neural plate, neural groove, neural tube, brain and spinal cord axes, neural tube layers, development of neurons and glia
• Neural crest - orogins
• Epidermis - ectoderm origins

Development Overview

Notochord

• 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.

Ectoderm

• 2 parts
• midline neural plate
  • columnar
• lateral surface ectoderm
  • cuboidal
  • sensory placodes
  • epidermis of skin, hair, glands, ant. pituitary, teeth enamel

Neural Plate

• 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- 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
• 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 inetraction- generates Neural strips

Neural Groove

• forms in the midline of the neural plate (day 18-19)
• either side of which are the neural folds which continues to deepen until about week 4
• neural folds begins to fuse, beginning at 4th somite level

Neural Tube

• the neural tube forms the brain and spinal cord
• fusion of neural groove extends rostrally and caudally
• begins at the level of 4th somite
• closes neural groove "zips up" in some species.
  • humans appear to close at multiple points along the tube.
• leaves 2 openings at either end - Neuropores
  • cranial neuropore closes before caudal

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

Neural Tube Defects (NTD)

• • failure of neural tube closure
  • severity dependent upon level, spina bifida anancephaly (More? 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

Neural Crest Notes

• 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

Primary Vesicles

• rostral neural tube forms 3 primary brain vesicles (week 4)
• 3 primary vesicles: prosencephalon (forebrain), mesencephalon (midbrain), rhombencephalon (hindbrain)

Secondary Vesicles

From the 3 primary vesicles developing to form 5 secondary vesicles

• prosencephalon- telencephalon (endbrain, forms cerebral hemispheres), diencephalon (betweenbrain, forms optic outgrowth)
• mesencephalon
• rhombencephalon- metencephalon (behindbrain), myelencephalon (medullabrain)

Ventricles

MH - this will be covered in detail in later 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 chorioid plexus, lying within the ventricles
  • (More? [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

Identified by 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 Axis

• 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 Axis

• Dorsalin - ectoderm secretes a growth factor shown to 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

• 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

Ectodermal Placodes

• Specialized ectodermal "patches" in the head region
• Contribute sensory structures - otic placode (otocyst), nasal placode, lens placode
• Contribute teeth

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

UNSW Embryology Links

• Neural Lecture 5 2008
• Neural Notes
• Neural Crest Notes
• System Notes
• Development Timeline

Internet Links

Embryo Images Early Cell Populations and Establishment of Body Form | Nervous System Development

Society for Neuroscience http://web.sfn.org/content/Publications/BrainFacts/index.html Brain Facts

Anatomy of the Human Body The Neural Groove and Tube

Glossary Links

A | B | C | D | E | F | G | H | I | J | K | L | M | N | O | P | Q | R | S | T | U | V | W | X | Y | Z

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