ORGANOGENESIS

Organogenesis - general

Organs and Organogenesis

1. Uniqueness

a. Origin - germ layer(s)

b. Position

c. Structure

d. Function

2. Organ primordia form from a specific germ layer (sometimes layers), usually in the region of the body where the organ will be located.

3. Differentiation ===> Histogenesis ===> Function

4. Organogenesis involves

a. inductions

b. migration of cells in some instances

c. shape change (at both cellular and tissue levels)

d. changes in cellular gene activity - differentiation/histogenesis

e. growth - organ size, cell number

f. in some cases, cell death

5. All these factors work in concert to “mold” the primordium into a functional organ.

Organogenesis - general

ORGANOGENESIS - ECTODERM

Figure on P. 234 of text.

Neurulation (human embryo)

http://courses.temple.edu/neuroanatomy/lab/embryo/ntube.htm

1

1

1

Amphibian neurulation movie from digital lab manual.

Neural Crest Cells1. Multipotent cells that arise from the edges of the forming neural plate

2. Migrate throughout body to form many different tissues/structures.

3. Two paths of migration

a. Dorsolateral (superficial pathway)

b. Ventral (deep pathway, between, around and through the somites)

http://www.erin.utoronto.ca/~w3bio380/lecture16.htm

4. Neural crest cells from cranial region form:

a. Sensory components of cranial nerves V, IX, X

b. Schwann cells

c. Contribute to branchial cartilages

d. Contribute to membranous bones of skull

e. Dentine of teeth

f. Contribute to head mesenchyme

g. Cranial parasympathetic ganglia

h. Ciliary muscles of eye

i. Meninges of CNS (dura mater, arachnoid, pia mater)

Neural Crest Cells

http://www.nlm.nih.gov/medlineplus/ency/imagepages/19080.htm

5. Neural crest cells from truck region form:

a. Parasympathetic and sympathetic ganglia

b. Dorsal root ganglia

c. Meninges of CNS (dura mater, arachnoid, pia mater)

d. Schwann cells

e. Adrenyl medulla

6. How can they become so many different things?

7. Multiple inductions along their paths of migration.

Neural Crest Cells

Neural crest cell migration in the chick hindbrain.

Neural crest cells leave from near the midbrain (m), midbrain/hindbrain boundary (m/h) and rostral rhombomeres (r1 and r2) and spread out to cover a wide region adjacent to the neural tube. Duration: 7 hrs Time interval between images: 3 min

http://dev.biologists.org/cgi/content/full/127/6/1161/DC1

“On Old Olympus’ Towering Top A Finn And German Vaulted And Hopped”

Olfactory (I), Optic (II), Oculomotor (III), Trochlear(IV), Trigeminal (V), Abducens

(VI), Facial (VII), Acoustic (VIII),

Glossopharyngeal (IX), Vagus (X), Accessory (spinal accessory) (XI),

Hypoglossal (XII)

Cranial NervesMnemonic

Froiep’s ganglion

petrosal (distal)

vestibulo-acoustic

Froiep’s ganglion

geniculate

superior (proximal) & petrosal (distal)jugular (proximal) & nodose (distal)

neural crest (superior) & epibranchial placode (petrosal)

Origin of the Cranial Ganglia

The Neural Tube (primordium of the CNS)

Shape change of cells as the neural plate forms

Figure on P. 236 of text

Shape change in cells.

Figure on P. 239 of text

http://courses.temple.edu/neuroanatomy/lab/embryo/histo.htm

Central nervous system development.

Later cell division in the neural tube cellsOutside

Establishes the ependymal, mantle and marginal layers.

Text

Figure similar to that on P. 439 of text - spinal cord development

Outside

Establishes the ependymal, mantle and marginal layers.

PATHFINDING BY AXONS

A. General neuron structureMyelination In CNS - oligodendrocytes In PNS - Schwann cells

B. Neurons and synapses

Hibbard, 1965 - pathfinding by axons in amphibian and fish hindbrain (medulla).

Anterior Anterior

Posterior Posterior

Figures on about Pp. 103 - 104 of lecture packet.

Hibbard, 1965 - pathfinding by axons in amphibian and fish hindbrain (medulla).

Anterior Anterior

Posterior Posterior

Figures on about Pp. 103 - 104 of lecture packet.

Hibbard, 1965 - pathfinding by axons in amphibian and fish hindbrain (medulla).

Anterior Anterior

Posterior Posterior

Figures on about Pp. 103 - 104 of lecture packet.

Mechanisms for axon pathfinding

1. Stereotropism (contact guidance)

a. Singer et al., 1979 - stereotropic pathfinding in neuroepithelial matrix of a newt embryo (amphibian)

b. Silver and Sidman, 1980 - stereotropic pathfinding in mouse retina

2. Differential adhesion (integrins, cadherins)

a. Letoureau, 1975 - diff. Adhesive pathfinding in vitro.

3. Galvanotropism

a. Patel et al., 1984 - pathfinding along charge differential pathways in vitro.

4. Chemotropism (netrin, connectin, nerve growth factor)

a. Gunderson & Barrett, 1979, 1980 - pathfinding in response to chemical signals in vitro.

“Axons locate their target tissues by using chemical attractants (blue) and repellants (orange)”

Either diffusable substances released by cells or molecules embedded in the plasmalemma

Surfaces of target tissue cells can also display attractant or repellent molecules.

Illustration by Lydia Kibiuk, Copyright © 1995 Lydia Kibiuk.

Axon Pathfinding - chemotropism http://web.sfn.org/content/Publications/BrainBriefings/axon.html#fullsize

Blue - attractant molecules

Orange - repellent molecules

The Growth Cone

“A false color image of a single cultured growth cone indicates high relative concentrations of fibrillar actin with warm colors.”

http://www.med.upenn.edu/nscience/neuro_raper.html

http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=.03cBD2-FFdfVWnQJpKKPvZlVwKDW-iGpTJ5qSw5u

The growth cone

http://www.anat.cam.ac.uk/pages/staff/academic/holt/images.html

http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=0mVzBEg1EX_YMkzpc2FN_TNTHWJTpj89DoajBTA4

As growth cones reach a point in axon growth where a decision must be made, they change shape and speed of growth and become more active. Filopodia appear to be searching for the right signal.

Optic chiasma

http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=0mVzBEg1EX_YMkzpc2FN_TNTHWJTpj89DoajBTA4

(Optic chiasma) (Optic chiasma)

One possible signal at the optic chiasma is a glycoprotein called CD44. If CD44 is not expressed or if the cells that express it are eliminated, the growing axons from the sensory retina ganglion cells do not cross the chiasma.

Examples of the effect of molecular signals on growth cone progress - Research by David Sretavan M.D., Ph.D., Doctor of Opthalmology University of California, San Francisco

http://ucsfeye.net/dsretavanresearch.shtml

Growth of retinal axons in mice in response to specific retinal proteins

Eph type proteins - can modulate axon pathfinding. Have attractive or repulsive effects on axon growth.

“The following QuickTime movies show retinal axon growth cones responding to gradients of Eph type proteins.

Videos presented at 420 times normal axon growth rate.” i.e., 1.5 min = about 10 hr

The human brain

By the sixth prenatal month, nearly all of the billions of neurons (nerve cells) that populate the mature brain have been created, with new neurons generated at an average rate of more than 250,000 per minute.

http://www.futureofchildren.org/information2827/information_show.htm?doc_id=79339

At birth - 100 billion neurons in brain = 100,000,000,000

1000 billion glial cells = 1,000,000,000,000

However, the wiring of the brain is not yet complete at birth.

As a baby starts to experience life, connections are made between cells - the more connections there are, the more the brain can do. Much of the brain’s growth after birth is due to the development of numerous dendrites that receive synaptic connections.A baby's brain develops so fast that by age two a child who is developing normally has the same number of connections as an adult.  By age three, a child has TWICE as many brain connections as an adult. http://www.preschoolrainbow.org/brain-growth.htm

Adult - an average of 10,000 synapses per cortical neuron

Very rough estimate,

10,000 synapses/neuron X 100,000,000,000 neurons

= 1,000,000,000,000,000

= 1000 trillion synapses in the adult brain

There is nowhere near enough information in your DNA to code for the specific locations of all these synapses.

Much of this “wiring” is completed after birth and results from the child’s interactions with his/her environment.

The human brain

Use it or lose it! Synaptic connections are winnowed as children grow. Those not used are lost while those that are used are retained. (Neurotrophic factors produced by the cell that grew the axon are necessary to maintain the synapse).

Practice makes perfect. This is true for young children and also, to a certain extent, when you get older.

The more you do something, the better you get (e.g., practice improves your hand-eye coordination).

Does this apply to other aspects of nervous development?

Developing coordination

Totally incompetent

Virtuoso

Genetically set limits

Environmentally determined outcome

Influence of Inheritance and Environment on ability

WHY IS THIS IMPORTANT?

BECAUSE YOU WANT YOUR CHILDREN TO BE

ALL THAT THEY CAN BE!!!!!

Inductions in the peripheral nervous system

Inductions in the peripheral nervous systemOlfactory epithelium

1. Formation of olfactory placode

a. Induction #1 - presumptive head endoderm

b. Induction #2 - presumptive head mesoderm

c. Induction #3 - telencephalon - seals fate

2. Cells of olfactory epithelium form stem cells, neurons and supportive cells

3. Olfactory neurons extend axons to olfactory lobes in telencephalon

4. Pathfinding by axons

5. Synapse on other neurons in olfactory lobes

6. Neurons in epithelium have a life-span of about 1 month

7. Must be replaced from stem cells

8. Axons are constantly extending from these new neurons into the olfactory lobes where new synapses are formed.

Inductions in the peripheral nervous system

Otic vesicle/inner ear

1.Induction #1 - Chordamesoderm passes near presumptive otic placode tissue

2. Induction #2 - nearby paraxial (somitomere) mesoderm further conditions cells

3. Induction #3 - Lateral wall of myelencephalon - seals fate and causes placode to form

DEVELOPMENT OF THE EYE

Lens placodeLens placode

Human - 7 - 8 wks

choroid fissure

(muscles)

opticoel

Human ~ 10 wks

vitreous body

(muscles)

neuroblastic

Development of the Human Retina

neuroblastic

Development of the Human Retina

neuroblastic

neuron

neuroblastic

Development of the Human Retina

Outer neuroblastic layer

Inner neuroblastic layer

Innermost neuron layer

Development of the Human Retina

lens

the

lens

added