UNSW Banner

UNSW Embryology

 ANAT2341 - Embryology - Lecture 16

© Dr Mark Hill (2009)

Acknowledgements

Introduction

endochondral bone

Lecture Notes under Development (notice removed when completed)

This lecture is an introduction to the process of skeleton formation and how connective tissue differentiates to form cartilage and then bone through ossification.

Developing Bone in the limb

(More? Carnegie Stages)

Page Links: Introduction | Lecture Slides | Lectopia Audio | Lecture Objectives | UNSW Embryology | Comments | Online Books | Internet Links | Next | Glossary | Terms |

Lecture Slides

These links are to PDF versions of the Lecture slides: 1 slide/page viewing 48 pages | 4 slide/page printing 12 pages | 6 slide/page printing 8 pages.

Lectopia Audio link to the audio recording of Lecture 16 Bone

The online text Online Books and UNSW Embryology links listed on this page worth reviewing for this lecture.

Lecture Objectives

Lecture Summary

The following text is extracted and modified from previous lecture slides and should be used as a "trigger" to remind you of some key concepts.

BMP2- Clinical Studies
Implantation of recombinant human BMP-2 (rhBMP-2)
can augment alveolar ridge in animal models when placed in a periodontal environment
restore new bone and attachment tissues
Clinical studies support ability of rhBMP-2 implants to induce physiologic bone
The bone morphogenetic protein family: multifunctional cellular regulators in the embryo and adult. Wozney JM. Eur J Oral Sci. 1998 Jan;106 Suppl 1:160-6. Review
Potential applications and delivery strategies for bone morphogenetic proteins. Kirker-Head CA. Adv Drug Deliv Rev. 2000 Sep 15;43(1):65-92. Review

Bone Abnormalities
Abnormalities
Congenital Hip Dislocation
Instability: 1:60 at birth; 1:240 at 1 wk: Dislocation untreated; 1:700
congenital instability of hip
later dislocates by muscle pulls or gravity
familial predisposition female predominance
Growth of femoral head, acetabulum and innominate bone are delayed until the femoral head fits firmly into the acetabulum
Abnormalities- Scoliosis
assymetric growth impairment of vertebral bodies
lateral deviation of spine
Lateral flexion
Forward flexion
Rotation of vertebral column on long axis
compensated by movement of vertebral column above and below affected region
producing a primary and two secondary curves
progresses rapidly in adolescence
becomes fixed once bone growth is completed
Hox2a Knockout
Synergistic Interactions
mouse skeleton (a)
sternum (b)
regions affected by short ear (se) and brachypodism (bp) mutations
Synergistic Interactions
se and bp mutations
affect different parts of mouse skeleton
coloured red and blue, respectively
se/se; bp/bp double mutants show the sum of individual phenotypes and also the sternum is affected (green)
se and bp gene products, BMP5 and GDF5, respectively, have a synergistic effect in sternal development
Abnormalities FGF receptors

UNSW Embryology

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:Bone Development | Limb Development | Axial Skeleton Development | Bone Development | Skull | Development Limb | Axial Skeleton| Human Bone | Endochondral Ossification | Skeletal Muscle | Cartilage |
Joints

The search window below allows a search within the UNSW Embryology website.

Coordinator Comments

Dr Mark Hill

Dr Mark Hill

Connective tissues develop from mesoderm and neural crest within the embryo. I this lecture we will look at mainly cartilage and bone development. Note there are two main issues relating to how bone is patterened and how bone then differentiates. In general we see cartilage differentiation before we see ossification which occurs later in development, and continues postnatally.

I have included detailed molecular mechanisms, you only need a genearl understanding.

These lecture pages are being updated for the current course, so it is worth coming back again later to see if any changes have occurred. Please let me know by email of broken links or content that is not clearly covered in this supporting online material.

Online Books

Devopmental Biology cover Developmental Biology 6th ed. Gilbert, Scott F. Sunderland (MA): Sinauer Associates, Inc.; c2000.

Below are listed links that relate to this Lecture from the textbook "Developmental Biology" which is available free online. You can either click the provided links or do your own search using the search link.

Search Developmental Biology

MBoC cover Molecular Biology of the Cell 4th ed. Alberts, Bruce; Bray, Dennis; Lewis, Julian; Raff, Martin; Roberts, Keith; Watson, James D. New York and London: Garland Publishing; c2002.

Below are listed links that relate to this Lecture from the textbook "Molecular Biology of the Cell" which is available free online. You can either click the provided links or do your own search using the search link.

Search Molecular Biology of the Cell
Bone Is Continually Remodeled by the Cells Within It
Image: Figure 22-52. Deposition of bone matrix by osteoblasts.
Image: Figure 22-56. The development of a long bone.

Molecular Cell Biology
Mutations in Collagen Reveal Aspects of Its Structure and Biosynthesis

The Cell- A Molecular Approach
Steroid Hormones and the Steroid Receptor Superfamily

Anatomy of the Human Body (H. Gray, 1918.)
Osteology

Clinical Methods: The History, Physical, and Laboratory Examinations
100. Alkaline Phosphatase and Gamma Glutamyltransferase

Endocrinology: An Integrated Approach by Nussey, S.S. and Whitehead, S.A.

Endocrinology: Definition and causes of osteoporosis

Internet Links

Course Homepage | Course Calendar | Course Handout 2008 - PDF Document (8 pages, 192Kb) | Textbooks | Journals

Online References

UWA Blue Histology Skeletal Tissues - Bone

University of Kansas Histoweb Bone

Loyola University Medical Education Network Part 9: Specialized Connective Tissue: Cartilage and Bone | Part 10: Endochondral Ossification

UNSW Embryology Cartilage and Bone

NCBI Bookshelf | Acrobat Reader

Next

Lecture 17 - Sensory Development Wed 13:00 - 14:00 Australian School Business 119 (K-E12-119)

Glossary

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

Terms

annulus fibrosus - the circularly arranged fibers (derived from sclerotome)that together with the nucleus pulposus (derived from notochord) form the intervertebral disc (IVD) of the vertebral column.

axial mesoderm - (=notochord)

cartilage - connective tissue from mesoderm in the embryo forms the initial skeleton which is replaced by bone. In adult, found on surface of bone joints.

centrum - the primordium of the vertebral body formed initially by the sclerotome.

clavicle - (L. little key) bone which locks sholder to body.

cloacal membrane- at caudal (anal) end of gastrointestinal tract (GIT) where surface ectoderm and GIT endoderm meet forms the openings for GIT, urinary, reproductive tracts. (see also buccopharyngeal membrane)

connective tissue-

costotransverse -

costovertebral -

dermatome -

dermomyotome - dorsolateral half of each somite that forms the dermis and muscle.

ectoderm - the layer (of the 3 germ cell layers) which form the nervous system from the neural tube and neural crest and also generates the epithelia covering the embryo.

endochondrial ossification - the process of replacement of the cartilagenous framework by osteoblasts with bone.

epaxial myotome - the dorsal portion of the myotome that generates dorsal skeletal muscles (epaxial muscles).

erector spinae -

extracellular matrix - material secreted by and surrounding cells. Consists if fibers and ground substance.

fibroblast growth factors - (FGF) a family of at least 10 secreted proteins that bind membrane tyrosine kinase receptors. A patterning switch with many different roles in different tissues. (FGF8 = androgen-induced growth factor (AIGF)

fibroblast growth factor receptor - receptors comprise a family of at least 4 related but individually distinct tyrosine kinase receptors (FGFR1- 4). They have a similar protein structure, with 3 immunoglobulin-like domains in the extracellular region, a single membrane spanning segment, and a cytoplasmic tyrosine kinase domain.

growth factor - usually a protein or peptide that will bind a cell membrane receptor and then activates an intracellular signaling pathway. The function of the pathway will be to alter the cell directly or indirectly by changing gene expression. (eg shh)

hox - (=homeobox) family of transcription factors that bind DNA and activate gene expression. Expression of different Hox genes along neural tube defines rostral-caudal axis and segmental levels.

hypaxial myotome - the ventral portion of the myotome that generates ventral skeletal muscles (hypaxial muscles).

intercostal- the region between adjacent ribs, usually comprising intercostal muscles and connective tissue.

intervertebral disc- (IVD) the annulus fibrosus+nucleus pulposus together form the intervertebral disc (IVD) of the vertebral column. This is the flexible region between each bony vertebra that allows the column to be bent.

intervertebral foramina-

lumbar plexus - mixed spinal nerves innervating the lower limb form a complex meshwork (crossing).

mesoderm - the middle layer of the 3 germ cell layers of the embryo. Mesoderm outside the embryo and covering the amnion, yolk and chorion sacs is extraembryonic mesoderm.

myoblast - the undifferentiated mononucleated muscle cells that will fuse together to form a multinucleated myotube, then mature into a muscle fibre.

MyoD - transcription factor involved in the determination of muscle cells in the somite. A basic helix-loop-helix factor which binds DNA.

myotome - the portion of the dermamyotome that generates skeletal muscle. Has 2 components epaxial (dorsal muscles ) hypaxial (ventral muscles).

neural crest - cell region at edge of neural plate, then atop the neural folds, that remains outside and initially dorsal to the neural tube when it forms. These paired dorsal lateral streaks of cells migrate throughout the embryo and can differentiate into many different cell types(=pluripotential). Those that remain on the dorsal neural tube form the sensory spinal ganglia (DRG). Neural crest cells migrate into the somites.

osteoblast - The mesenchymal cells that differentiate to form the cellular component of bone and produce bone matrix. Mature osteoblasts are called osteocytes. (More? Musculoskeletal Development - Bone)

osteoclast - Cells that remove bone (bone resorption) by enzymatically eroding the bone matrix. These cells are monocyte-macrophage in origin and fuse to form a multinucleated osteoclast. These cells allow continuous bone remodelling and are also involved in calcium and phosphate metabolism. The erosion cavity that the cells lie iwithin and form is called Howship's lacuna. (More? Musculoskeletal Development - Bone)

osteocyte - The mature bone-forming cell, which form the cellular component of bone and produce bone matrix. Differentiate from osteoblasts, mesenchymal cells that differentiate to form bone. (More? Musculoskeletal Development - Bone)

osteon - The anatomical (histological) unit structure (principal structure) of compact bone. (More? Musculoskeletal Development - Bone)

Pax - name derived from Drosophila gene 'paired' (prd) the 'paired box' is a amino end 124 amino-acid conserved domain (signature aa 35-51: P-C-x(11)-C-V-S). Transcription factor of the helix-turn-helix structural family, DNA binding, and activating gene expression. In human, nine member proteins from Pax-1 to Pax-9. Regulate differentiation of many different tissues. Some members of the family (PAX3, PAX4, PAX6, PAX7) also contain a functional homeobox domain.

pedicle -

primary centre of ossification - the first area where bone growth occurs between the periosteum and cartilage.

sacrum -

sclerotome - ventromedial half of each somite that forms the vertebral body and intervertebral disc.

segmentation - to break a solid structure into a number of usually equal size pieces.

somatic mesoderm - derived from lateral mesoderm closest to the ectoderm and separated from other component of lateral mesoderm (splanchnic, near endoderm) by the intraembryonic coelom.

somite - segmental block (ball) of mesoderm formed from paraxial mesoderm adjacent to notochord (axial mesoderm). Differentiates to form initially sclerotome and dermamyotome (then dermotome and myotome).

somitic mesoderm-

somitocoel - a transient cavity that appears within each of the the early forming somites then is lost.

somitogenesis - the process of segmentation of the paraxial mesoderm to form "mesoderm balls" beginning cranially (humans day20) and extending caudally at 1 somite/90 minutes until approx. 44 pairs have been formed.

sonic hedgehog - (=shh) secreted growth factor that binds patched (ptc) receptor on cell membrane. SHH function is different for different tissues in the embryo. In the nervous system, it is secreted by the notochord, ventralizes the neural tube, inducing the floor plate and motor neurons. In the Limb it is secreted by the zone of polarizing activity (ZPA) organizing limb axis formation.

tarsal -

Tbx - T-box genes (transcription factor) involved in mouse forelimb (Tbx4) and hindlimb (Tbx5) specification.

transcription factor- a factor (protein or protein with steroid) that binds to DNA to alter gene expression, usually to activate. (eg steroid hormone+receptor, Retinoic acid+Receptor, Hox, Pax, Lim, Nkx-2.2).

transverse abdominal m.-

trochanter-

vertebral body- formed by centrum, vertebral arch, facets for ribs. It is the mature vertebral structure formed by the 5 secondary ossification centers after puberty.

vertebral column - name given to the complete structure formed from the alternating segments of vertebra and intervertebral discs which support the spinal cord.

vertebral foramen - the dorsal cavity within each vertebra, generated by the vertebral arch that surrounds the spinal cord.

vertebral canal -

Wnt7a - The designation 'Wnt' was derived from 'wingless' and 'int'. The Wnt gene was first defined as a protooncogene, int1. Humans have at least 4 Wnt genes: Wnt7a gene is at 3p25 encoding a 349aa secreted glycoprotein. A patterning switch with different roles in different tissues. The mechanism of Wnt distribution (free diffusion, restricted diffusion and active transport) and all its possible cell receptors are still being determined. At least one WNT receptor is Frizzled (FZD). The Frizzled gene family encodes a seven-transmembrane receptor.

References

These references are background reviews and research article readings and is not examinable.

Search PubMed: term= bone+development | endochondrial ossification | intramembranous ossification | osteoblast | cartilage+development

Some Recent Reviews

Pogue R, Lyons K. BMP signaling in the cartilage growth plate. Curr Top Dev Biol. 2006;76:1-48.

Mundy GR, Elefteriou F. Boning up on ephrin signaling. Cell. 2006 Aug 11;126(3):441-3.

Franz-Odendaal TA, Hall BK, Witten PE. Buried alive: how osteoblasts become osteocytes. Dev Dyn. 2006 Jan;235(1):176-90. Review.

Li Z, Kong K, Qi W. Osteoclast and its roles in calcium metabolism and bone development and remodeling. Biochem Biophys Res Commun. 2006 May 5;343(2):345-50. Epub 2006 Mar 6.

Roodman GD. Regulation of osteoclast differentiation. Ann N Y Acad Sci. 2006 Apr;1068:100-9.

Mackie EJ. Osteoblasts: novel roles in orchestration of skeletal architecture. Int J Biochem Cell Biol. 2003 Sep;35(9):1301-5.

Ducy P. Cbfa1: a molecular switch in osteoblast biology. Dev Dyn. 2000 Dec;219(4):461-71. Review.

Articles

Prefumo F, Canini S, Crovo A, Pastorino D, Venturini PL, De Biasio P. Correlation between first trimester fetal bone length and maternal serum pregnancy-associated plasma protein-A (PAPP-A). Hum Reprod. 2006 Nov;21(11):3019-21.

Nakaoka R, Hsiong SX, Mooney DJ. Regulation of chondrocyte differentiation level via co-culture with osteoblasts. Tissue Eng. 2006 Sep;12(9):2425-33.

Iqbal J, Sun L, Kumar TR, Blair HC, Zaidi M. Follicle-stimulating hormone stimulates TNF production from immune cells to enhance osteoblast and osteoclast formation. Proc Natl Acad Sci U S A. 2006 Sep 26

Sun L, Peng Y, Sharrow AC, Iqbal J, Zhang Z, Papachristou DJ, Zaidi S, Zhu LL, Yaroslavskiy BB, Zhou H, Zallone A, Sairam MR, Kumar TR, Bo W, Braun J, Cardoso-Landa L, Schaffler MB, Moonga BS, Blair HC, Zaidi M. FSH directly regulates bone mass. Cell. 2006 Apr 21;125(2):247-60. "Postmenopausal osteoporosis, a global public health problem, has for decades been attributed solely to declining estrogen levels. Although FSH levels rise sharply in parallel, a direct effect of FSH on the skeleton has never been explored. We show that FSH is required for hypogonadal bone loss"

Bruzzaniti A, Baron R. Molecular regulation of osteoclast activity. Rev Endocr Metab Disord. 2006 Sep 2;

Hutchison C, Pilote M, Roy S. The axolotl limb: A model for bone development, regeneration and fracture healing. Bone. 2006 Aug 17;

UNSW Embryology ISBN: 978 0 7334 2609 4

UNSW CRICOS Provider Code No. 00098G