Vertebral column patterning is based upon the rostrocaudal sequential differentiation of the paired somites. The column differentiates from the paired sclerotome component (ventral half) of the somite and the midline ventral patterning structure the notochord (More? Axial Skeleton). Therefore much of early vertebral column molecular development is covered in somite differentiation (More? Mesoderm/Somite).
 |
 |
Sclerotome surrounding neural tube |
Within each somite 3 distinct temporally transient structures form (dermomyotome, myotome and sclerotome), only the ventromedial portion known as the sclerotome contributes the axial vertebral column. Note that the myotome also contributes the supporting vertebral column muscular structures. The sclerotome has been described as undergoing an "epitheliomesenchymal transition" and differentiation is regulated by a number of surrounding tissues including: notochord, neural tube, lateral plate mesoderm, and myotome. Later differentiation of the vertebra and intervertebral disc involves a half somite shift of the initial segmentation caudally.
 |
 |
Developing Vertebral "bony collar" |
Developing Intervertebral Disc |
The vertebral column, like other skeletal structures, forms as a cartilagenous template that is later converted into bone by endochondral ossification. (More? Bone | Endochondral Ossification). Ossification leaves an articular cartilage which remains adjacent to the intervertebral disc. The intervertebral disc differentiates as a fibrocartilage disc.
The best animal models of vertebral development are chicken (Christ B, etal., 2004) and mouse.
Other suggested terminologies identifying transient sclerotome developmental features are: syndetome, neurotome, meningotome, and arthrotome (Christ B, etal., 2004).
syndetome - sclerotomal subdomain from which tendons develop
arthrotome - somitocoele-derived sclerotomal subdomain from which forms the vertebral joint
meningotome - narrow medial-most zone of the sclerotome immediately adjacent to the lateral surface of the neural tube form the meninges surrounding the spinal cord
neurotome - cranial half of the developing sclerotome invaded by outgrowing axons and neural crest cells and differentiate to form the perineurium and endoneurium
Stage 22 Vertebra with dorsal uniting membrane or ligament
The dorsal part of the developing laminae of the vertebral arches do not fuse but are united by a connective tissue membrane (dorsal uniting membrane or ligament). The presence of this ligament allows continued spinal cord growth.
Page Links: Introduction | Some Recent Findings | Cartilage Molecular Development | Bone Molecular Development | General_Axes | Ventral | Dorsal | Rostro-Caudal | References | Search PubMed | WWW Links | Glossary
Other Pages: Musculoskeletal Development - Axial Skeleton | Musculoskeletal Development - Axial Skeleton | Musculoskeletal Development - Mesoderm/Somite | Musculoskeletal Development - Bone | Musculoskeletal Development - Endochondral Ossification | Body Axes - Early | Body Axes - rostro/caudal | Body Axes - anterior/posterior | Body Axes - Left/Right | Limb Axes | Vertebrae Development Movie
Pickett EA, Olsen GS, Tallquist MD. Disruption of PDGFRalpha-initiated PI3K activation and migration of somite derivatives leads to spina bifida. Development. 2008 Feb;135(3):589-98.
"Genetic disruption of platelet-derived growth factor receptor (PDGFR) alpha results in spina bifida, but the underlying mechanism has not been identified. ...results indicate that PDGFRalpha downstream effectors, especially PI3K, are essential for cell migration of a somite-derived dorsal mesenchyme and disruption of receptor signaling in these cells leads to spina bifida."
Wahl MB, Deng C, Lewandoski M, Pourquié O. FGF signaling acts upstream of the NOTCH and WNT signaling pathways to control segmentation clock oscillations in mouse somitogenesis. Development. 2007 Nov;134(22):4033-41.
Somitogenesis Review Article - Shifley ET, Cole SE. The vertebrate segmentation clock and its role in skeletal birth defects. Birth Defects Res C Embryo Today. 2007 Jun;81(2):121-33.
"Molecular evidence for the existence of the segmentation clock was first described in the expression of Notch signaling pathway members, several of which are expressed in a cyclic fashion in the presomitic mesoderm (PSM). The Wnt and fibroblast growth factor (FGF) pathways have also recently been linked to the segmentation clock, suggesting that a complex, interconnected network of three signaling pathways regulates the timing of somitogenesis. ... at least two human disorders, spondylocostal dysostosis (SCDO) and Alagille syndrome (AGS), are caused by mutations in Notch pathway genes and exhibit vertebral column defects"
Ventral vertebral column normal formation of the cervical and lumbar region ventral vertebral elements (also scapula and sternum) requires expression of the transcription factor Paired box-containing gene 1 (Pax1) (Wilm B, etal., 1998). (Alternative Names: Paired Domain Gene HuP48; HUP48) Pax1 has also been shown as capable of substituting for Shh in induction of Bapx1 expression and therefore initiating chondrogenic differentiation (Rodrigo I etal., 2003). (Bapx1 - Bagpipe Homeobox, Homolog of Drosophila, 1) (More? Cartilage Development)
The Pax transcription factor family consists of 9 members (Pax1-Pax9) that all have a common motif of a paired domain (128 amino acids) required for DNA binding.
Sonic hedgehog and Noggin are the upstream regulators of Pax1. Pax9 has also been identified as having a similar role but has been described as functionally redundant.
Suggested Signalling Pathway (read from bottom to top)
Sox9 and Collagen II (cartilage markers)
↑
chondrogenesis
↑
Bapx1
↑
Pax1 and Pax9
↑
Sonic hedgehog and Noggin
↑
Notochord
Links: Factors - Shh | OMIM - Pax1 | OMIM - Bapx1 | Development - Figure 14.9. Model of major postulated interactions in the patterning of the somite |
The dorsal and lateral sclerotome develop later, do not express Pax1 and are controlled by Bone Morphogenic Protein 4 (Bmp4).
(Alternative Names: Bone Morphogenic Protein 2B, Bmp2B, Bmp2B1) (More? Molecular Factors - Bmp)
Msx1 - Muscle Segment Homeobox, Homolog of Drosophila, 1
Suggested Signalling Pathways
Roof Plate and Ectoderm
Bmp4 and Bmp2 (inhibits Pax1)
↓
Neural Tube (dorsal) → Pax3 → Msx1 and Msx2 (dorsal markers)
Mfh1
↑
Notochord
Links: Factors - Bmp | OMIM - Bmp4 | OMIM - Bmp2 | OMIM - Msx1 | OMIM - Msx2 |
Two current theories
For more details about cartilage development see Cartilage page and for specific information about the factors involved in muscle see the general Molecular Development page or use the links listed below.
Sclerotomal differentiation to cartilage (chondrogenesis) can be indicated by mesenchymal expression of Sox9 and Collagen II.
Hyaluronan receptor (CD44) - cell membrane glycoprotein, expression occurs at the time of reduction of intercellular spaces at sites prior to cartilage deposition. Signaling through this receptor pathway affects both chondrocyte survival and apoptotis.
Links: OMIM - CD44
Dicer - 21 nucleotide small regulatory RNA required in RNA interference and small temporal RNA (stRNA) pathways to produce the active small RNA component that represses gene expression.
Links: OMIM - DICER | Pubmed Review
For more details about bone development see Bone page and for specific information about the factors involved in bone development see the general Molecular Development page or use the links listed below.
The transcription factor Core Binding Factor 1 (Cbfa1) plays an essential role in osteoblast differentiation, bone formation, matrix production and mineralization.
Reviews
Shifley ET, Cole SE. The vertebrate segmentation clock and its role in skeletal birth defects. Birth Defects Res C Embryo Today. 2007 Jun;81(2):121-33.
Yusuf F, Brand-Saberi B. The eventful somite: patterning, fate determination and cell division in the somite. Anat Embryol (Berl). 2006 Dec;211 Suppl 1:21-30.
Christ B, Huang R, Scaal M. Formation and differentiation of the avian sclerotome. Anat Embryol (Berl). 2004 Aug;208(5):333-50.
Articles
Pickett EA, Olsen GS, Tallquist MD. Disruption of PDGFRalpha-initiated PI3K activation and migration of somite derivatives leads to spina bifida. Development. 2008 Feb;135(3):589-98.
Wahl MB, Deng C, Lewandoski M, Pourquié O. FGF signaling acts upstream of the NOTCH and WNT signaling pathways to control segmentation clock oscillations in mouse somitogenesis. Development. 2007 Nov;134(22):4033-41.
Rodrigo I, Hill RE, Balling R, Münsterberg A, Imai K. Pax1 and Pax9 activate Bapx1 to induce chondrogenic differentiation in the sclerotome. Development. 2003 Feb;130(3):473-82.
Peters H, Wilm B, Sakai N, Imai K, Maas R, Balling R. Pax1 and Pax9 synergistically regulate vertebral column development. Development. 1999 Dec;126(23):5399-408.
Furumoto TA, Miura N, Akasaka T, Mizutani-Koseki Y, Sudo H, Fukuda K, Maekawa M, Yuasa S, Fu Y, Moriya H, Taniguchi M, Imai K, Dahl E, Balling R, Pavlova M, Gossler A, Koseki H. Notochord-dependent expression of MFH1 and PAX1 cooperates to maintain the proliferation of sclerotome cells during the vertebral column development. Dev Biol. 1999 Jun 1;210(1):15-29.
Wilm B, Dahl E, Peters H, Balling R, Imai K. Targeted disruption of Pax1 defines its null phenotype and proves haploinsufficiency. Proc Natl Acad Sci U S A. 1998 Jul 21;95(15):8692-7.
Search PubMed: Search April 2008 "vertebral column developmental patterning" 81 reference articles of which 15 were reviews. vertebral column developmental patterning | vertebra patterning | sclerotome development |
This current page has additional windows that allow searching of OMIM Morbid Map and OMIM Gene Map and access to other External WWW Search pages (Medical dictionaries, glossaries, chemicals and drugs).
DNA Notes there is a window to search the Human Genome by keyword and also to search for a specific species classification.
In the DNA Notes there is also a page with 3 search windows for Nucleotide Sequence, Protein Sequence and Biomolecule 3D Structure from NCBI.
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
The first page of Developmental and System Notes usually contains some information about mechanisms of development that include molecular mechanisms. In order to keep the introductory page simple, detailed molecular mechanisms have been placed on a separate page (Page 11) of each section of notes. Below is a list of direct links to specific Molecular Development Pages.
| Molecular System Notes |
|
| Axis Formation | Early | Limbs |
|
Signaling during development, though complex, can also be grouped into a few specific classes. These mechanisms have also been listed and described briefly on Signaling Mechanisms page.
Lecture Notes |
Please note that these notes only relate to an earlier Course and not all Lecture notes and research material have been transferred. |
| |
Simple pictures illustrating the early events of fertilization. |
| |
Figures and text relating to early events of spinal cord formation. |
| |
Text relating to the molecular events of sex determination in the embryo. |
| |
A short comparison of establishing positional information in embryos. |
| |
The fly mutation that opened the field of Hox Genes and the conservation of pattern formation control mechanisms between species in embryonic development. |
Home Page
Embryo stages
Fetal Dev
Dev Notes 1
Dev Notes 2
System Notes
Acknowledgements
Movies
Class Notes
Serial Images
K12 Students
Abnormal
Embryology in the News
Histology
Site Map
Epigenetics
X Inactivation
Signalling
Embryo Axis
Early Axis
Rostro/Caudal Axis
Anterior/Posterior Axis
Left/Right Axis
Limb Axes
Spinal Cord Axes
Vertebral Column
Sex Determination
Reviews
School of Med Sci
UNSW Medicine
University of NSW
UNSW Cell Biology
NCBI Books
Dev Biol (Gilbert)
This section of notes introduces the topic of vertebral column axes formation. There are other notes which discuss the spinal cord (neural) development.
Initial signals are about axial pattern formation of embryonic tissues, while later development requires an understanding of cartilage, bone and fibrocartilage tissue differentiation.
Please email Dr Mark Hill if you wish to make a comment about this current project.