Difference between revisions of "2009 Lecture 6"

From Embryology
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* 3 components form: floor plate, neural plate, neural crest  
 
* 3 components form: floor plate, neural plate, neural crest  
  
Neural Determination- Neural Plate
+
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
  
* neuronal populations are specified before plate folds
+
Neural Determination- Neural populations  
** signals from notochord and mesoderm
+
* neuronal populations are also specified before plate folds  
** secrete noggin, chordin,follistatin
+
* lateral inhibition generates at spinal cord level 3 strips of cells  
* all factors bind BMP-4 an inhibitor of neuralation
+
* expression of delta inhibits nearby cells, which express notch receptor, from becoming neurons  
** bone morphogenic protein acts through membrane receptor Neural Determination- Neural populations  
+
* Delta-Notch- generates Neural strips  
** neuronal populations are also specified before plate folds  
+
 
** lateral inhibition generates at spinal cord level 3 strips of cells  
+
===Neural Groove===
** expression of delta inhibits nearby cells, which express notch receptor, from becoming neurons  
+
* forms in the midline of the neural plate (day 18-19)  
** Delta-Notch- generates Neural strips '''Neural Groove'''
+
* either side of which are the neural folds which continues to deepen until about week 4  
** forms in the midline of the neural plate (day 18-19)  
+
* neural folds begins to fuse, beginning at 4th somite level  
** either side of which are the neural folds  
+
 
** continues to deepen until about week 4  
+
===Neural Tube===
** neural folds begins to fuse  
+
* the neural tube forms the brain and spinal cord
** at 4th somite level '''Neural Tube'''
+
* fusion of neural groove extends rostrally and caudally  
** fusion of neural groove extends rostrally and caudally  
+
* begins at the level of 4th somite  
** begins at the level of 4th somite  
+
* closes neural groove "zips up" in some species.
** "zips up" neural groove
+
** humans appear to close at multiple points along the tube.
** leaves 2 openings at either end- Neuropores
+
* leaves 2 openings at either end - '''Neuropores'''  
** forms the brain and spinal cord '''Secondary Neuralation'''  
+
** cranial neuropore closes before caudal
** caudal end of neural tube formed by secondary neuralation  
+
 
** develops from primitive streak region  
+
===Secondary Neuralation===
** solid cord canalized by extension of neural canal  
+
* caudal end of neural tube formed by secondary neuralation  
** mesodermal caudal eminence '''Neuropores'''
+
* develops from primitive streak region  
** cranial neuropore closes before caudal
+
* solid cord canalized by extension of neural canal  
 +
* mesodermal caudal eminence
  
 
===Neural Tube Defects (NTD)===
 
===Neural Tube Defects (NTD)===

Revision as of 15:23, 10 August 2009

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

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

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 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

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

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


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

Next Lecture

Lab 3 | Lecture 7 | Course Timetable

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