17 Toward a Spinal CordOntology

Charles Watson and Amandeep SidhuThis chapter is a speculative introduction to the creation of a

new nomenclatural hierarchy for the spinal cord – an ontology.

We have recently been engaged in the construction of

mammalian brain ontology based on the avian schema

presented by Puelles et al., (2007). During this study, we were

struck by the fact that the current spinal cord nomenclature is

inconsistent with the developmental subdivisions of the spinal

cord revealed by modern molecular genetics (Raff, 2000;

Carpenter, 2002; Cohn and Tickle, 1999; Guthrie, 2004; Dasen

et al., 2005).

What is an ontology?The concept of ontology was borrowed from the realm of

philosophy by artificial-intelligence researchers and has since

become a subject of interest to computer and information

scientists in general. In computer science literature, the term

takes on a new meaning, but one that is not entirely unrelated

to its philosophical counterpart. There are many different

ontology definitions in the computer and information science

literature (Pretorius, 2004), but all researchers agree on the

importance of ontology research in terms of the necessary

mechanisms to represent, share, and reuse the existing domain

knowledge (Gómez-Pérez et al., 2003). A frequently cited

definition of ontology is that of Thomas R. Gruber (Gruber,

1993). He states that:

“A body of formally represented knowledge is based on a

conceptualization... A conceptualization is an abstract, simplified

view of the world that we wish to represent for some purpose.

Every knowledge base, knowledge-based system, or knowledge-

level agent is committed to some conceptualization, explicitly or

implicitly. An ontology is an explicit specification of a

conceptualization.”

The difference between ontology and a knowledge base can be

described in terms of their different objectives. Ontology aims

to capture the conceptual structures of a domain, while a

knowledge base aims to specify a concrete state of the domain.

The purpose of ontology is to describe facts assumed to be

always true by a community of users. A generic knowledge base

may also describe facts and assertions related to a particular

state of affairs. For an agent, a shared ontology describes a

vocabulary for communicating about a domain. In contrast,

a knowledge base contains the knowledge needed to solve

problems or answer queries about such a domain by

committing to an ontology. Ontology is, in the first

approximation, a table of categories, in which the collection of

nodes within a hierarchical tree captures every type of entity

within that domain.

Regional subdivisions in the spinal cordThe traditional regional subdivision of the spinal cord is based

on the levels of cervical, thoracic, lumbar, sacral, and coccygeal

vertebrae. The boundaries of these vertebral regions correlate

roughly with the functional regions of the cord, but the

discrepancies are significant. For example, the expanded

ventral horn which houses the forelimb motoneurons begins

at the fourth or fifth cervical spinal cord segment in most

mammals and the root of the lowest segment emerges not

below the last cervical vertebra, but below the T1 vertebra.

Likewise, the region containing sympathetic preganglionic cells

in rodents usually begins at the segment whose nerves emerge

belowT2 (not T1) and ends at the segment whose roots emerge

below L1 or L2, not below T13. In both cases, the functional

transition level disregards the ‘vertebral’ transition level. On

the other hand, the functional regions correlate well with

regions of Hox gene expression in the limb enlargements and

in the sympathetic preganglionic region (Raff, 2000; Carpenter,

2002; Guthrie, 2004; Dasen et al., 2005). The Hox gene

expression territories can be conveniently observed in acetyl

cholinesterase (AChE) or choline acetlyltransferase (ChAT)

preparations, which highlight the anatomy of the somatic and

preganglionic motoneurons (see Chapters 15 and 16).

A new regional classification based on developmentWe propose a different regional classification based on the

distinct areas of gene expression and AChE/ChAT staining that

define the limb enlargements and the sympathetic and

parasympathetic preganglionic groups as an alternative to the

‘vertebral’ classification. This new scheme clearly clashes with

the traditional cervical, thoracic, lumbar, sacral, coccygeal

designations, but is true to the developmental processes. Unlike

the traditional classification, it can be applied to a range of

species that have different numbers of cervical, thoracic or

lumbar vertebrae, and takes into account intraspecific

variation, such as ‘prefixing’ and ‘postfixing’ of limb

enlargements.

The system is founded on the assumption that the basic plan in

mammals and birds is to have a group of five major spinal cord

segments supplying the forelimb, followed by a long group of

segments with sympathetic preganglionic neurons, which is in

turn followed by a group of five major spinal cord segments

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supplying the hindlimb. The hindlimb group is immediately

followed by two or three segments containing the

parasympathetic neurons. In most mammals, the forelimb

group is preceded by four segments, which contain the

branchial motoneurons of the accessory nerve and the phrenic

nucleus. The parasympathetic group is succeeded by the part

of the spinal cord, which supplies the tail muscles.

We suggest that the new subdivisions be called prebrachial,

brachial, interramal, crural, postcrural, and caudal.

• ‘Prebrachial’ refers to the region between the caudal end of

the brainstem and the brachial enlargement. In mammals

this is represented by spinal cord segments C1 to C4. This

region contains the branchial motoneurons of the

accessory nerve that supply trapezius and

sternocleidomastoid. It also contains most of the phrenic

nucleus motoneurons.

• ‘Brachial’ refers to the forelimb (brachial) enlargement,

typically five segments long in birds and mammals. It is

characterized by the presence of a lateral motor column

(LMC). In almost all mammals it extends from segment

C5 to T1.

• ‘Interramal’ refers to the region between the limb

enlargements. This region is characterized by absence of an

LMC the presence of preganglionic sympathetic neurons.

In rodents it extends from segment T2 to L1.

• ‘Crural’ refers to the hindlimb (lumbar) enlargement. It is

typically 5 segments long. It is characterized by the

presence of an LMC. In rodents it typically extends from

segment L2 to L6, and in humans from segment L2 to S1

(humans normally have only five lumbar segments).

• ‘Postcrural’ refers to the two or three sacral segments that

contain preganglionic parasympathetic neurons. In rodents

this region extends from segment S1 to S2; in humans it

extends from segment S2 to S4.

• ‘Caudal’ refers to the part of the spinal cord caudal to the

sacral preganglionic parasympathetic neurons. This region

supplies the tail muscles. In rodents it extends from

segment S3 to the last coccygeal segment.

An ontological outline of spinal cordnomenclatureThe following is an outline of the way our proposed spinal

cord ontology is arranged. The ontology has 6 levels, with the

sixth level representing individual neuron groups. Level 1 is the

level of the brain vesicles and the spinal cord. At the suggestion

of Luis Puelles, there is at Level 4 a division of the developing

neural tube into roof plate, alar plate, liminal region, basal

plate, and floor plate (Puelles et al., 2007). These groupings

work well in the subdivision of the prosomeres, midbrain,

isthmus and rhombomeres, but we are as yet unsure of their

complete application to the spinal cord ontology.

The abbreviations for cell laminae or cell clusters (the

components of level 6 of the ontology) are those that are

represented in the plates and drawings of the rat and mouse

spinal cord atlases (see Chapters 15 and 16).

Six levels in the spinal cord ontologyIn this section we present the level 1 and 2 subdivisions of the

whole spinal cord, and the level 3, 4, 5, and 6 components of

only a single segment (C8) to show the way the tree extends

down to local cell groups at level 6 (see Chapters 15 and 16 for

explanation of abbreviations used here). See Figure 17.1.

Subdividing the limb enlargements intorostral and caudal groupsA further step in this classification could be to divide each of

the limb enlargements into rostal and caudal parts, according

to anatomical differences (see Chapters 15 and 16) and gene

expression (e.g. Dasen et al. 2005). Five segments supply most

of the input to the upper and lower limb enlargements in most

mammals (segments C5 to T1 for the upper limb and

segments L2 to L6 for the lower limb in rodents). In each case,

the rostral two segments are notably different from the caudal

three segments. Note that for the purposes of this argument,

we have chosen to ignore the small contribution of segment C4

to the upper limb enlargement, and the contribution of

segment L1 to the lower limb enlargement.

The similarities between the gray matter in the upper and

lower limb enlargements are striking. If one examines the

ventral horn in isolation, it is easy to confuse segment C6 with

L3, C8 with L5, and so on.

Detailed similarities between thearrangement of motoneuron groups in the brachial and lumbar enlargementsWhile each limb enlargement in mammals consists primarily

of five segments that contain limb motoneurons (C5 to T1 for

the upper limb and L2 to L6 for the lower limb in rodents),

there is a distinct difference between the rostral two segments

and the lower three segments. In the case of the upper limb,

there are only two main clusters of motoneurons in the upper

two segments – the dorsally placed biceps group and the

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ventrally placed deltoid group. In the case of the lower limb,

the picture is very similar; segments L2 and L3 have only two

main groups of motoneurons – the quadriceps/iliopsoas group

ventrally and the adductor/gracilis group dorsally.

In the lower three segments of the brachial region (C7 to T1),

four major motoneuron groups supplying the limb can be

identified – a ventromedial group supplying the pectoralis

major, a ventrolateral group supplying the triceps, a

dorsolateral group supplying the forelimb extensors, a

dorsomedial group supplying the forelimb flexors. Four groups

of in a similar pattern can be identified in the lumbar segments

L4 to L6 of the lower limb enlargement – a ventromedial group

supplying the hamstrings, a ventrolateral group supplying the

gluteal muscles, a dorsolateral group supplying the crural

extensors, and a dorsomedial group supplying the crural

flexors. In the brachial and lumbar enlargements, the

dorsolateral and dorsomedial groups coalesce in the most

caudal segment (T1 in the upper limb; L6 in the lower limb) to

form a distinct round group of motoneurons that supply the

manus and pes respectively.

The study of gene expression in the chick brachial enlargement

by Dasen et al., (2005), supports a subdivision into rostral and

caudal regions on the basis of Hox gene and Hox transcription

factor expression patterns. Ryan et al., (1998) have

demonstrated that the pattern of motoneuron clusters and

their relationship to forelimb muscle groups is highly

conserved in vertebrate evolution. They demonstrated that the

forelimb motorneuron patterns in a reptile, a bird, and a

mammal were very similar.

Similarities between the segments thatimmediately precede the upper and lowerlimb enlargementsAnother feature shared by the two limb enlargements is the

presence of a specialized motor nucleus in the segment

immediately rostral to the enlargement. In the case of the

brachial enlargement, this is the phrenic nucleus, with a very

compact group of cells lying in the centre of the dorsal horn at

segment C4, with extensions into segments C3 and C5. In the

case of the lumbar enlargement, there is a nucleus of strikingly

similar appearance to the phrenic in the same relative position.

This is the cremaster nucleus, mainly located in L1 but with

extensions into L2 and T13. The similarity between the phrenic

and cremaster nuclei is most clearly seen in horizontal ChAT

sections, which emphasize the tight packing of the

motoneurons and the bundling of their dendrites.

382 The Spinal Cord Watson, Paxinos & Kayalioglu

Level 1Spinal cord

Level 2Prebrachial (segments C1 to C4) This is the regionsupplying the neckBrachial (C5 to T1) The forelimb enlargement

Level 3C8

Level 4Roof plateAlar plate

Level 5lamina 1

1Splamina 2

2Sp2SpO2SpI

lamina 33Sp

lamina 44Sp

lamina 55Sp5SpM5SpL

Level 4Basal plate

Level 5lamina 6

6SpIMM

lamina 77Sp

lamina 88Sp

lamina 999Tr (triceps motoneurongroup)9Pec (pectoralis motoneurongroup)9LD (latissimus dorsimotoneuron group)9FFl (forearm flexormotoneuron group)9FEx (forearm extensormotoneuron group)9Ax (axial muscle motoneurongroup)

lamina 1010Sp

Level 4Floor plate

Interramal (segments T2 to L1) This is the regionbetween the two limb enlargements, which contains thesympathetic preganglionic neurons.

Crural (segments L2 to L6) – this is the hindlimbenlargement

Postcrural (segments S1 to S2) – this is the sacralparasympathetic zone

Caudal (segments S3 to Co3) – the region thatinnervates the tail

Figure 17.1 Six levels in the spinal cord ontology

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Does this spinal cord ontology have any practical application?In a perfect world, new logical concepts would rapidly replace

the old. But in reality, old uses that have served us well are hard

to displace. The failure of the Dvorak keyboard to replace the

QWERTY keyboard is an excellent example of such resistance

(Gould, 1991). Because of this, we do not think that there will

be a rapid movement toward the use of ‘interramal’ in

preference to ‘thoracic’. However, it is possible that

developmental biologists will appreciate the utility of an

ontology that is independent of species variation in vertebral

morphology.

We also acknowledge that clinical neurologists and other

clinicians are no more likely to adopt this scheme (even if they

heard about it) than they are to recognize the rhombomeric

subdivisions of the hindbrain and the existence of the isthmus

(see Puelles et al., 2007 for discussion of these issues). But in

the end, serious researchers should be drawn to nomenclatural

usage that has heuristic value and serves to clarify the issues

they are investigating. We are optimistic.

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