Paper - The development of the auditory nerve in vertebrates: Difference between revisions

From Embryology
mNo edit summary
Tag: New redirect
 
(20 intermediate revisions by the same user not shown)
Line 1: Line 1:
{{Header}}
#REDIRECT [[Paper - The development of the auditory nerve in vertebrates (1910)]]
{{Ref-CameronMilligan1910}}
{| class="wikitable mw-collapsible mw-collapsed"
! Online Editor  
|-
| [[File:Mark_Hill.jpg|90px|left]] This 1910 paper by Cameron and Milligan is a historic description of auditory nerve development.
<br>
 
See also -
 
'''Modern Notes:''' [[Hearing - Neural Pathway]]
<br>
{{Hearing Links}}
|}
{{Historic Disclaimer}}
=The Development of the Auditory Nerve in Vertebrates=
JOURNAL OF ANATOMY AND
PHYSIOLOGY
 
THE DEVELOPMENT OF THE AUDITORY NERVE IN VERTEBRATES. By JOHN CAMERON,l\I.D.,D.SC.,L6Ct1m“e’I" on Anatomy,
1l[l(fl(l/l8.S‘€.7} Hospfltal Illerlicail School; and WILLIAM MILLIGAN, M.D.,
Leotm"e1r on Di8e(L»ses of the’ Ear, U 77/lversity of Jllcmchesterg Am°7}st
<m(l Lcm°y/ngologist to the Royal I ‘I?’/fi’)'i‘171l11Cl/7”':I./, il[(lTlClL68l6’I“.
 
C O N T E N T S.
PAGE
I. INTRODUCTORY . . . . . . . . ‘ . . . . . 111
II. THE AUDITORY SYNCYTIUM . . . . . . . . . . 112
III. THE FURTHER ELABORATION or THE AUDITORY SYNCYTIUM . . . 115
 
IV. THE a-, 3-, AND 7-NEUROBLASTS or THE AUDITOR1’ SY1\'CYTIUM AND NERVE 121
V. THE NAscENT AND THE MATURE PHASES OF THE AUDITORY NERVE-AxoNs 124
 
VI. THE “VULNERABLE POINT” OF THE AUDITORY NERVE . . . . 127
VII. THE MODE OF CONTINUITY OF THE AUDITORY SENSE-EPITHELIUM WITH THE
 
NUCLEI IN THE HIND BRAIN . . . . . . . . . . 128
 
VIII. SUMMARY . . . . . . . . . . . . . . 130
 
I. INTRODUCTORY.
 
IN 1906 the authors read a paper before the Otological Society of the
United Kingdom on the development of the auditory nerve, founded o11a
study of the embryos of a few vertebrate types ((5). This was meant to
partake of the nature of a preliminary communication, as it was deemed
advisable to secure material representing all the great vertebrate classes
before embarking upon a more pretentious publication. The work has
been considerably delayed owing to the difficulty Which Was experienced
in obtaining a supply of representative embryos. This hindrance has,
however, been of service in permitting us to make an extensive comparative
study of the developing auditory nerve throughout vertebrates.
 
It may be stated at the very outset that our results afibrd unequivocal
support to the multicellular theory of nerve genesis. Evidence in support of this theory has been previously advanced by one of us in the case of the optic nerve (8) and the spinal nerves (10). The conclusions arrived at as a
consequence of the present investigation are thus confirmatory of these
previous observations. The auditory nerve was chosen for the purpose of
the present research for two reasons. With the view, firstly, of ascertaining
embryologically the mode of continuity of the fibres of this nerve with the
sense-epithelium on the one hand, and the cells in the nuclei of the hind
brain on the other. The second reason for choosing the auditory nerve was,
that it affords a favourable opportunity for investigating the question of
nerve histogenesis, as in this case the end organ and the central nervous
system are in close association with one another from the early developmental stages.
 
Meth0ds.——The embryos were fixed in Bles’ fluid, and cut transversely
to their long axes. The sections thus produced were mounted serially, and
subsequently stained on the slides. After several experiments it was
ascertained that the iron-alum-haematoxylin method of Heidenhain, slightly
modified, demonstrated the nerve fibrils to the most favourable degree, and
this was finally chosen as the chief colouring agent. The achromatic and
chromatised phases of the primitive axis cylinders, to be referred to in the
 
subsequent description, were found to be very clearly defined by this mode
of staining.
 
II. THE AUDITORY SYNCYTIUM.
 
The earliest rudiment of the auditory nerve consists of a large mass of
cells developed from the cephalic portion of the neural crest. This is
termed the facial-acoustic ganglion (or complex of American authors),
which early divides into its component elements, the facial portion forming
of course the geniculate ganglion. The auditory portion takes up its
position between the hind brain and the developing otic vesicle. We made
a series of reconstructions of the latter in the various vertebrate types
examined, and found that the ganglion rudiment became applied to it in
such a way as to come into intimate relationship with, on an average, about
one-third of its superficial area (figs. 1 and 2). A further study of this
relationship in the more advanced stages brought into prominence the
interesting fact that this is the only portion of the wall of the otic vesicle
from which the special sense-epithelium is derived, the cells of the remainder
undergoing retrogression and flattening to form the characteristic arrangement seen in the adult. This area, which will be hereinafter referred to as
the sense-epithelium patch, .exhibits active karyokinesis, so that it is
evidently destined to form the essential auditory cell-elements of the
membranous labyrinth.
 
On turning to an examination of the auditory ganglion itself by high
Development of the Auditory Nerve in Vertebrates 113
 
powers of the microscope (,1; and 1% , it could be clearly established in all
the vertebrate types that, at a certain stage, this consisted of a mass of
nuclei imbedded in an apparently structureless and comparatively achromatic cytoplasm. The latter was readily traceable through the incomplete
membrana limitans externa of the hind brain with the scanty cytoplasm
of the neuroblasts there (fig. 3), ‘and, on the other hand, with the rudiments
of the sense-epithelium in the otic vesicle through its equally imperfect
membrana limitans externa (fig. 4). It is obvious, then, that the cell elements in the sense-epithelium patch of the otic vesicle are brought into close association with those of the hind brain in early embryonic life by a continuous tract of nucleated cytoplasm (fig. 5). The only title by which one can adequately denote the latter is syncytium. We have therefore
decided to adopt this term in place of “ ganglion ” for the early stages of
development. This decision is still further justified by the fact that the
cells -of the spiral ganglion and the ganglion of Scarpa represent a quite
insignificant proportion of those constituting the acoustic ganglion, as will
be indicated in the subsequent description.
 
 
 
fiG. 1.—The relationship of the auditory syn- fiG. 2.—A neighbouring section to fig. 7, showing
cytium to the hind brain and otic vesicle in a. the relationship of the auditory syncytium to
frog embryo of 8 mm. the otic vesicle. .
 
 
 
This intimate connection of the otic vesicle With the hind brain in the
early phases of development is in close agreement With the observations of
Graham Kerr on the motor nerves of Lcpidosiren embryos (14). This
authority describes the existence of a protoplasmic “ bridge ” between the
spinal cord and the myotome, which becomes fibrillated later to form the
114 Dr John Cameron and Dr William Milligan
 
motor tract between the central nervous system and the end organ. This
is the crux of the whole question of nerve genesis. The upholders of the
unicellular theory of nerve origin have undoubtedly been misled through a
failure to recognise the existence of this bridge. The latter was certainly
prominent in the case of the spinal nerves of frog and chick embryos
studied by one of us (10), and also in the optic nerve of frog embryos (8).
Indeed, the term syncytium might be applied to the appearance presented
by the nerve in the latter instances just as appropriately as in the case of
the auditory nerve. We would venture to suggest at this stage that the full recognition of the syncytial phase of nerve histogenesis means the
abandonment of the unicellular theory in favour of the multicellular.
 
 
 
fiG. 3. Junction of the a.uditory syncytium with fiG. 4.—Junction of the auditory syncytium with
the wall of the hind brain in an 8-mm. frog the wall of the otic vesicle in an 8-mm. frog
embryo. embryo.
 
 
 
This View of primitive nerve structure is likewise in close accord with
those of Bethe (4) and (5), Apathy (1) and (2), Fragnito (11), and Schultze
(20). It is also significant to point out at this stage that Sedgwick (21)
some years ago drew attention to the fact that the developing tissues of
the embryo are connected together by a continuous reticulum. Thus he
showed that the neuroblasts of the neural tube are in direct continuity
with the cell-elements‘ of the surrounding mesoblast through the medium
of this network. Sedgwick’s work was adversely criticised at the time;
but we have no hesitation in placing our seal on the accuracy of his
observations. A good deal of the trouble has arisen from embryologists
Development of the Auditory Nerve in Vertebrates 115
 
having insisted for years on the three-layered condition of the early
embryo. After all, the mesoblast is really derived from the epiblast and
hypoblast, We consider that it is much more accurate to regard the
embryo as a homogeneous whole, somewhat after the idea of Sedgwick.
More recently still, Bernard (3) has demonstrated that the cell-elements of
the retina, not only those belonging to one layer, but also those of neighbouring layers, are brought into close. association with one another by means of a system of delicate interconnecting fibrils. To this he gives the
name of protomitomic system.
 
 
fiG. 5. -The continuity of the peripheral auditory tract in a 13-mm. frog embryo.
 
 
 
III. THE FURTHER ELABORATION or THE AUDITORY SYNCYTIUM.
 
The description of the mode of development of the auditory nerve in
text—books of embryology is very brief. So far as one can gather, the
main purport is to the effect that the cells of the acoustic ganglion become
divided up in some mysterious way into two groups which ultimately
become the constituent elements of the spiral ganglion and the ganglion of
Scarpa on the cochlear and vestibular divisions of the nerve. The ganglion
 
cells are afterwards described as giving ofl central and peripheral axis ,
 
cylinder processes which pass to the cells of the hind brain and the
developing sense-epithelium respectively,
116 Dr John Cameron and Dr William Milligan
 
Our results are opposed to this current view of the mode of development
of the auditory nerve. It will be recognised at the very outset that the
commonly accepted interpretation of what takes place obviously does not
explain the division of the ganglionic mass into its two main elements,
seeing that the latter operation occurs previous to the development of the
fully formed axis cylinders. The real explanation is found in a further
study of the developing otic vesicle. The latter rapidly expands in surface
area during the early stages, and very soon becomes constricted off into
the utricle and saccule. This constriction passes through the senseepithelium patch of the vesicle and divides it into two portions, each of
which bears away the part of the auditory syncytium attached to it. The
division of the latter is thus brought about by the fact that the end organ
and hind brain must have been previously in intimate association with one
another through the medium of the syncytium.
 
We studied this splitting up of the auditory syncytium first of all in
fish embryos, as in these the otic vesicle does not undergo the degree of
elaboration found in higher vertebrates. A favourable opportunity was
thus afforded of observing the exact relationship which the syncytium
bears to the sense-epithelium patch of the otic vesicle. figs. 6, 7, 8, 9 and
 
10 are camera, lucida tracings of the otic vesicle and auditory syncytium
of an embryo of Oyclopterus lumpus, a teleost. They represent Nos. 96,
98, 100, 102, and 104 of a series of transverse sections, numbered from the
cephalic end. The syncytium, which is coloured red, will be observed in
fig. 6 (section N o. 96) to correspond in size with the thickened senseepithelium patch of the otic vesicle, with the cell-elements of which it is
in intimate relationship. In fig. 7 (section No. 98) the patch has divided
into two areas, with a thinned portion of the vesicle wall between, and so
likewise has the syncytium; the result being that the latter is still
maintaining its close association with both. A In figs. 8 and 9 (sections
Nos. 100 and 102) the two sense-epithelium patches are still seen, whilst
the attachment of the syncytium to the wall of the hind brain is likewise
clearly indicated. In fig. 10 (section No. 104) the two patches have become
completely separated, but the syncytium is preserving its intimate attachment to both. In the same figure a third patch has made its appearance
on the semicircular canal in the lower part of the labyrinth, and it, in its
turn, is in close association with an offshoot from the main syncytial mass.
From a further examination of embryos of Cyclopterus lwmpus it was
ascertained that these subsidiary sense-epithelium patches were all derivatives of the originally single area, with which the auditory syncytium was
in continuity during the early developmental stages (fig. 11).
 
We consider that these above observations, which were confirmed by a study of the otic vesicle in embryos representing the higher vertebrate
classes as well, clearly established the fact that the breaking up of the
auditory gaiiglioii” is a necessary acconipaninient of the process of
resolution of the sense-epithelium patch into its various component macular
areas. Inasmuch as the latter are  many as six in higher inammals, it
follows that the syncytium must likewise divide into a similar number of
links connecting these with the hind brain, and constituting the l’u11(la1nental
divisions of the auditory nerve. Thus an examination of the otic Vesicle
oi’ teleostean fishes revealed the fact that the primary sense-epithelium
patch divided into areas for each of the three semicircular canals, the two
maculze of the utricle, the saccule, and the patch at the lzig<;+1i:1, the
 
 
 
Development of the Auditory Nerve in Vertebrates
 
Sense-epithelium ,3
patches of otic /’
 
     
 
' _‘ vesicle (black).
Auditory syncytium (red). Sense-epithelium patch ‘~
Of Obie Vesicle (b19«0k)- Auditory syncytium (red).
fiG. 6. t - ' Fla. 7.
Optic lobe. '
 
   
 
Hindbrain. Auditory Sense-epithelium patches
syncytium (red). of otic vesicle (black).
 
fiG. 8.
Optic lobe. Optic lobe.
 
 
 
   
 
Sense-epithelium
_ patches of otic
x vesicle (black).
 
“~ Auditory
syncytium (red).
 
\
\
 
‘ “~ Auditory syncytium (red).
Hind brain’ Hind‘ brain. \‘
 
\
 
fiG’ 9' Sense-‘epithelium patches
 
. of otic vesicle (black).
fiG. 10.
 
 
 
fig ]1.——Diagran1 to show the relation of the auditory syncytium to the
hind brain and otic vesicle in an early vertebrate embryo.
 
remainder of the cochlea being quite rudimentary. The auditory syncytium
followed suit, and resolved into a corresponding number of component
parts, ‘ix’. seven in all  12). On iisivestiga-tiirg‘ the condition in
amphibians, we found that the sense-epithelium patch of the otic vesicle
divided into areas for the three semicircular canals, the two maculie of the
utricle, the macula of the saccule, and the patches for the cochlear canal
:l»1l(]lli1gC1l£L. Each of these, as usual, bore away with it a portion of the
syncytium, which thus became subdivided into eight portions (fig. 13).
 
In birds a process similar to that in amphibians was found to take place,
our observations on embryos of this class of vertebrates confirining the
description in a recently published book on the development of the chick
by Lillie (17). Thus on page 295 that author states that “the acoustic
ganglion from which the auditory nerve arises, takes its origin from the
acoustico—facialis ganglioii which lies in front of and below the centre of
Development of the Auditory Nerve in Vertebrates 119
 
the auditory pit. During the closure of the latter the acoustic ganglion
becomes fused with part of the Wall of the otocyst in such a Way that it
becomes impossible to tell in ordinary sections where the epithelial cells
 
   
 
     
 
fiG. 12.—Diagram to show the seven areas into which the sense-epithelium
patch of the otic vesicle divides in higher fishes, as also the corresponding subdivisions of the auditory nerve with their ganglia.
 
leave ofi and the ganglion cells begin. This fused area may be called the
auditory neuro-epithelium. . . . The neuro-epithelium is the source of all
 
 
 
 
fiG. 13. —Diagram to show the eight areas into which the sense—epithelium
patch of the otic vesicle divides in amphibians and birds, as also the
corresponding subdivisions of the auditory nerve with their associated
 
ganglia.
 
the sensory areas, wl1icl1 arise from it by growth and subdivision. The
branching of the auditory nerve follows the subdivision of the neuroepithelium.
 
On studying the question in embryos of mammals, including man, the
120 Dr John Clameron and Dr \Villian1 Milligan
 
sense-epithelium patch of the otic vesicle was as usual observed to be in
intimate association with the auditory syncytium. The former, as development proceeded, resolved into six areas for the semicircular canals, the
utricle, saccule, and cochlea. Simultaneously with this, the auditory
syncytium l)ccame broken up into six corresponding parts each of which
remained in continuity with that portion of the otic Vesicle wall it was
originally in association with  14). It was particularly interesting to
study the way in which the developing cochlear canal dragged off its
quotum of the syncytium with it. As the canal elongated and became
coiled on itself, so also the syncytium was compelled to do likewise. The
development of the auditory nerve in man has been so well described recently by Streeter (22) that we do not propose to enter into any further
details here. We will refer further to this observer’s work in section V.
of this paper. From the foregoing remarks it follows that it is obviously
inaccurate to describe the auditory ganglionic mass as consisting of cochlear
and vestibular portions, since these are not the fundamental elements of the
nerve, however convenient these terms may appear when considered from
the point of view of their physiology.
 
 
 
 
fig. 14.~I)iagra1n to show the six areas i11to which the sense-epithelium
patch of the otic vesicle divides in higher mammals, as also the
correspomling subdivisions of the auditory nerve with their associated ganglia.
 
 
 
His (12) described the nerves to the saccule and posterior semicircular
canal as being derived in the human embryo from the cochlear division of
the auditory ganglion. Certainly the arrangement of the foramina in the
la1ni11a cribrosa of the internal auditory meatus would lead one to infer
that this view was correct. For example, the nerves to the cochlea and
those to the saccule and posterior semicircular canal all pass through below
Development of the Auditory Nerve in Vertebrates 121
 
the falciform crest, whilst those for the superior andexternal canals and
the utricle make their exit above the crest. Streeter (22), however, pointed
out that the filaments to the saccule and posterior canal are not developed
from the cochlear division of the auditory nerve, but are derived from a
portion of the ganglionic mass which forms the vestibular division.
 
The arrangement of the foramina in the lamina cribrosa in man is
readily explained by studying the relative positions of the sense-epithelium
patches on the membranous labyrinth. Such an examination will show
that the macula of the utricle and the ampullae of the superior and external
semicircular canals are close together, and therefore the nerves to these all
pass through the area cribrosa superior. On the other hand, the macula of
the saccule and the ampulla of the posterior canal are placed at a lower
level and also much further apart, relatively speaking, so that the nerve
filaments to these traverse the area cribrosa media and the foramen singulare,
which are likewise separated by a slight interval.
 
IV. THE 01-, ,8-, AND y-NEUROBLASTS or THE AUDITORY SYNCYTIUM AND NERVE.
 
The existence during embryonic life of three types of neuroblasts in the
central nervous system has been demonstrated in a recent paper (9). These
make their appearance in a definite order and represent distinct phases in
the ontogeny of the nerve cell. To those met with in the earliest stages the
term a—neuroblast was given. These undergo varying degrees of elaboration during the later phases, so that one can then distinguish two subvarieties, to which the terms ,8- and y-neuroblasts were applied. Of these
the latter are readily distinguishable by the greater metabolic activity of
their nuclei. They become invested by a considerable cytoplasmic envelope
and thus develop into the nerve cells of such important regions as the
sensori—motor areas, the cornua of the spinal cord, etc. The B-neuroblasts
do not attain to such a degree of development, their cytoplasmic investment
is relatively scanty, and they occupy a position subsidiary to the y-variety,
both structurally and physiologically.
 
The a—, ,8-, and y—types of neuroblast could be readily identified in the
developing auditory ganglion. In the early phases the primitive ct-type
is, of course, the only representative. Their nuclei were found to exhibit
evidences of metabolic activity similar to those previously described for
neuroblasts in other parts of the developing nervous system. The most
remarkable sign of this metabolism in amphibian and fish embryos consisted in the ingestion by their nuclei of the particles of yolk with which
the tissues are loaded during the early developmental stages. This was
122 Dr John Cameron and Dr William Milligan
 
found to occur exactly after the manner adopted by neuroblast nuclei in
other parts of the central nervous system of these lower vertebrate types.
The existence of the “ assimilative pole” of these nuclei (9) could be readily
demonstrated, and in most cases this was the one directed towards the otic
vesicle (figs. 3 and 4). A further expression of the activity of these
 
nuclei was to be found in the products of their metabolism. Their cytoplasmic investment in the early stages is very scanty, in fact so much so
that it is often difficult to «convince oneself of its existence. Very soon,
however, they become surrounded by a clear and almost achromatic envelope, a considerable proportion of which is nuclear in origin. This
gradually increases in bulk and blends with similar material surrounding
neighbouring nuclei. The performance of this “ achromatin function” by
these neuroblast nuclei has been, previously described (9), so that it is not
intended to dilate further on this subject here. It will now be recognised
that the auditory syncytium is brought into being by the blending of this
new achromatic material to form one continuous nucleated mass uniting
the cell-elements of the otic vesicle with those of the hind‘ brain. We
consider that the amount of perinuclear substance is not sufficient in amount
to warrant the application of the term syncytium to the earliest developmental phases of the facial-acoustic ganglion.
 
 
 
 
 
fiG. l5.'—The direction of the plane of mitosis in the auditory
syncytium of a. rabbit embryo.
 
 
 
A third index of the activity of the nuclei of the auditory syncytium
is_ "afforded by the remarkably free karyokinesis which they exhibit. This
has been previously shown (10) to be one of the earliest signs of the
development of the spinal nerves, and it is a rather interesting coincidence
that it should also be prominently displayed in the case of the auditory
nerve. Moreover, the plane of division always occurs at right angles to the
line of the future nerve, as in the previous instances (fig. 15). r The result
of this active mitosis is to produce a great increase in the number of
cell-elements constituting the syncytium.
 
The further life-history of the a-neuroblasts, of which the auditory
syncytium is composed, will be found to display certain interesting features.
As development proceeds one can readily recognise a gradual evolution of
the ,8- and y-neuroblasts from the primitive type.
 
 
 
fiG. 16.——fibrillation of the peripheral end of the auditory syncytium
in a 13-mm. frog embryo.
 
The y-type will be readily recognised in three situations, namely, in the
hind brain, in the wall of the otic vesicle, and in the syncytium midway
between these points. Those in the wall of the otic vesicle form the senseepithelium, a better name for which is neuro-epithelium. These latter cells
must be regarded as neuroblasts of the highly evolved y-type. They
certainly satisfy all the requirements of this qualification. . Thus the nuclei
are large and spherical in the resting condition, whilst the cytoplasmic
investment is abundant, and exhibits fine fibrillae. The latter are continuous
with the fibrillae which develop in the distal portion of the auditory
nerve (fig. 16). _
 
The y-neuroblasts which tmake their appearance in the middle of the
syncytial bridge form the ganglia associated with the cochlear and
vestibular roots * of the auditory nerve. They constitute a very small
proportion of the neuroblasts of the original syncytium. The fibrillae
which develop in their cytoplasm are continuous with those in the
proximal and distal portions of the nerve. It will, however, be pointed
124 Dr John Cameron and Dr William Milligan
 
out presently that the latter are not formed from these neuroblasts, but
are independent formations in the previously undifferentiated syncytial
 
mass (fig. 17).
The y-neuroblasts which develop in the central end of the syncytium
 
‘form a large proportion of the nuclei of origin of the cochlear nerve fibres.
 
Their cytoplasm is abundant, as usual, and comes to possess delicate
fibrillae continuous with those laid down in the syncytium (fig. 18).
 
The ,8-neuroblasts represent by far the greater proportion of those
originally constituting the auditory syncytium, and will be found prominently displayed along the Whole course of the auditory nerve. Their
nuclei are small, oval in outline, and are applied along the line of the nerve
fibres (figs. 17 and 20). One has little difficulty in recognising that the
,8-neuroblasts become the cells of the nerve sheath and thus assume a
position subsidiary to those of the -y-type, both developmentally and functionally.
 
 
 
 
fiG. 17. -—The fibrillation of the intermediate portion of the auditory syncytiumin a
13-mm. frog embryo. g Note also the diflerentiation of the 3- and -y-neuroblasts.
 
 
 
 
V. THE NASCENT AND THE MATURE PHASES or THE AUDITORY
NERVE—AXONS.
 
It has been previously pointed out that one can recognise a nascent or
achromatic and a mature or chromatised ‘phase in the life-history of the
axons of the spinal nerves (10). The material which is laid down along
Development of the Auditory Nerve in Vertebrates 125
 
the path of the future nerve is at first quite homogeneous and undifferentiated, and thus merits the title of achromatic. It ought to be noted
however, that the latter term is applied merely in a comparative sense.
The mature or chromatised phase in the spinal nerves was shown to be
produced by a peculiar chemical alteration in the above material whereby
it became affected in a definite manner by staining agents. Treatment by
the latter exhibited the existence of a fine longitudinal fibrillation which
 
Coc1_11earr0ot of
..— :uu11to1-y nerve.
 
, , Developing
rcstiform body. ,
 
Vestihulal‘ 1-out
,» ot':111«lit0ry
nerve.
 
fih1'il1ati0n of
,’ syncytium.
 
fiG. 18. —fibrilla.tion of the central end of the auditory syncytium in a.
13-mm. frog embryo.
 
manifested itself simultaneously along the whole length of the nerve tract.
To this profound alteration the term “ chromatisation ” was applied.
 
We find that an exactly analogous change takes place in the case of
the auditory nerve. Thus the previously undifferentiated cytoplasm of the
syncytium becomes fibrillated simultaneously at all points of its course.
Further, this important change occurs at the same time that the fibrillae are
being laid down in the cytoplasm of the y—neuroblasts (fig. 17). Not only
so, but the primitive fibrillae -may be readily traced along the whole
auditory nerve tract, particularly in lower vertebrates (e.g. amphibian
126 Dr John Cameron and Dr VVilliam Milligan
 
embryos); whilst their continuity with the neuro—fibrillae of the y—neuroblasts in the hind brain with those in the middle of the tract and with
those of the neuro—epithelium can be freely established. This simultaneous
appearance of the fibrillae shows that they are not developed independently
of the syncytium as central and peripheral processes from the ganglion cells
in the middle of the nerve, which is the usually accepted view of their mode
of formation. Each fibrilla is exceedingly fine. Our impression is that the
future axon is at first represented by a single one of these, the remaining constituents being subsequently laid down by further processes of
chromatisation. The unit of nerve structure is, from this standpoint,
not the axis-cylinder, but the fibrilla. We have certainly been unable
to detect an outgrowth of fully developed axons from the cells of the
acoustic ganglion to form the central and peripheral processes of the
auditory nerve.
 
Unfortunately, our material was not in a sufiiciently good condition to
permit us to make any definite statement with reference to the process of
fibrillation in the auditory nerve of the human embryo. Wle were enabled,
however, to gather that the auditory syncytium, with its undifferentiated
cytoplasm, is as prominent in the human subject as it is in lower
vertebrate types. In this relationship it is interesting to quote Streeter’s
recent observations (22) on the developmentof the fibres of the auditory
nerve in the human embryo. Thus he states1 that “in the embryos
studied the proximal end of the nerve (cochlear nerve) could be made out
almost as soon  the distal. So it is possible that the cochlear trunk
consists originally of a column of ganglion cells connecting the anlage of
the spiral ganglion with the brain, and the conversion of this column into
fibroblasts produces the early fibres of the trunk; this would explain the
abrupt appearance of the nerve trunk in all parts of its course at once.”
Streeter’s conclusions with regard to the origin of the axis-cylinders of the
auditory nerve in the human embryo thus evidently agree with our own
results for lower vertebrate types. He was apparently much impressed by
the development of the fibrillae simultaneously along the whole course of
the nerve tract, and we are glad to be enabled to confirm his suggestions
regarding the real nature of neurogenesis. Streeter’s application of the
te1'111fib1°0blcLst.9 to certain of the cell—ele1nents in the auditory complex
appears to us rather felicitous. It will be recognised that these correspond
to the ,8-neuroblasts described by us.
 
The cytoplasm of the auditory syncytium does not become wholly
transformed into fibrils. The latter become congregated into groups to
form axis-cylinders, the undifferentiated portion of the cytoplasm surrounding these persisting as the medullary sheath. The ,8—neuroblasts are, of course, the precursors of the cells constituting the neurilemma.
 
VI. THE “VULNERABLE Po1NT” or THE AUDITORY NERVE.
 
That portion of the auditory syncytium which is situated next to the
hind brain undergoes a rather interesting alteration during development.
In this region the nuclei are very scanty, and the cytoplasm does not on
that account appear to increase in amount, seeing that it is in some measure
a derivative of nuclear activity. The result is that as the syncytial bridge
gradually lengthens owing to the continued growth of the tissues, this
portion becomes attenuated, and quite free from [3—neuroblasts (fig. 18).
Indeed, by the time fibrillation occurs its calibre has become decidedly less
than that of the remainder of the syncytium. The portion of the cytoplasm
in this region which does not become differentiated into fibrils persists as the
medullary sheath. Note, however, that since there are no ,8-neuroblasts
left in this segment of the nerve tract, there can be no development of a
neurilemma sheath. This explains why the latter terminates just before
the auditory nerve enters the hind brain. Owing to this deficiency in the
covering of the fibres, it is obvious that this segment must constitute a
weak spot in the nerve trunk. In this relationship it is rather significant
to study the results of Orr and Rows (18) on the lymphogenic origin of
toxic infection of the central nervous system. These observers have
demonstrated that, both in the spinal and cranial nerves in general
paralysis and other nervous affections, the degeneration commences in the
sensory roots just before they enter the central nervous system, that is,
exactly at the point where they lose their neurilemma sheath. Orr and
Rows have likewise found that, after the implantation of celluloid capsules
containing toxins in various parts of the body, the resulting degeneration of
the sensory fibres invariably started at this situation. They have accordingly termed this the “vulnerable point”; and there can be no doubt that
it is so, considered from a developmental standpoint as well. fig. 18,
which is drawn from a frog embryo, exhibits the early phase of fibrillation
of the auditory syncytium at its junction with the hind brain. Note
the degree of attenuation of this segment and its freedom from nuclei.
It is clear from the foregoing results that the neurilemma sheath
exercises an important protective as well as a nutritive influence over
nerve fibres.
 
Turning now to the study of the distal end of the developing auditory
nerve, it is found that an exactly similar alteration takes place there. Just
 
before the syncytium passes through the external limiting membrane of the
otic vesicle to become continuous with the cytoplasm of the neuro-epithelium,
it becomes attenuated (fig. 16) and also freed from the nuclei of the
B-neuroblasts in a manner similar to that Which occurs at the central end
of the nerve. The cytoplasm of the syncytial bridge in this region becomes
fibrillated as usual, and that Which remains undifferentiated forms the
medullary sheath. Here, as at the central end, the deficiency of neurilemma
sheath is explained by the absence of ,8-neuroblasts. It is therefore
obvious that this segment of the auditory nerve is likewise Weak and unguarded, so that no doubt toxins would find a ready entrance at this
point as well.
 
 
 
 
 
 
 
fiG. 19. The continuity of the ripheral auditory tract in a young frog.
 
Note the 7-neuroblasts of t e auditory ganglion. The hairs of the sense-epithelium are visible.
 
 
 
 
 
 
VII. THE MODE OF CONTINUITY or THE AUDITORY SENSE-EPITHELIUM WITH THE NUCLEI IN THE HIND BRAIN.
 
We have already pointed out that the auditory syncytium, the yneuroblasts in the hind brain, the neuro-epithelium and the y-neuroblasts
in the middle of the syncytial tract, become fibrillated simultaneously. The
resulting neuro-fibrillae thus form one continuous bond‘ of union between
the neuro-epithelium and the hind brain, This conclusion is in direct
Development of the Auditory Nerve in Vertebrates 129
 
antagonism to the usually accepted view of continuity of the peripheral
auditory tract. Thus Retzius (19), Lenhossék (15), Katz (13) and others
have shown, by means of the Golgi method, that the peripheral and central
fibres of the auditory nerve end in arborisations round the neuro-epithelium
 
‘and the cells in the hind brain respectively. It is surprising to note how
 
readily the appearances presented by Golgi preparations of the central
nervous system have been accepted by histologists Without question or
comment. Our results with this method on nerve endings have not been
 
fiG. 20.—The auditory ganglion and nerve and the hind brain of a. young
frog. Note the -y-neuroblasts of the ganglion and hind brain and
the B-neuroblasts of the nerve.
 
convincing enough to Warrant our placing implicit confidence in its use.
Its action on embryonic tissues is undoubtedly very disappointing. The
iron-alum-haematoxylin method is, to our Way of thinking, much more
satisfactory and more immune from ambiguity in the interpretation of the
appearances presented by the tissues. Certainly, in the embryos of vertebrates below the rank of man, this mode of staining demonstrates not a
contiguity by synapse but a direct anatomical continuity of the peripheral
auditory tract. Of course it is possible that the conditions which prevail
during embryonic life may become profoundly modified by the time full
maturity has been attained; but our investigations on more mature tissues
by the iron-alum-haematoxylin stain have so far convinced us that this is
130 Dr John Cameron and Dr VVilliam Milligan
 
not so. We have therefore decided to abandon the “idea of a synapse in
favour of that of a direct anatomical continuity of tissue. Thus the
intimate association which the auditory end organ bears to the hind brain
during the early stages through the medium of the auditory syncytium
never really becomes severed (figs. 5 and 19).
 
 
 
 
VIII. SUMMARY.
 
(1) The auditory end organ is brought into direct anatomical continuity
with the hind brain by means of a nucleated tract of cytoplasm to which
the authors have applied the term syneytrimn.
 
(2) The breaking up of the auditory nerve into its various divisions is a
necessary accompaniment of the differentiation of the Wall of the otic vesicle
into the various sense-epithelium patches, since each of the latter bears off
its quotum of the auditory syncytium with which it was originally in
intimate continuity.
 
Thus the cochlear and vestibular portions of the auditory nerve are
not its fundamental divisions. The latter are six in man, composed of one
for each semicircular canal, one for the utricle, one for the saccule, and one
for the cochlea.
 
(4) Three types of neuroblasts may be identified in the auditory syncytium. The term a-neuroblast has been adopted for those existing during
the early stages.”
 
(5) The 3- and y-neuroblasts are further elaborations of the a-type,
and represent distinct phases in the ontogeny of the nerve cell.
 
(6) The y-neuroblasts make their appearance in three situations, namely,
in the hind brain, in the Wall of the otic vesicle, and in the syncytial tract
midway between these points.
 
(7) The ,8—neuroblasts become the cells of the neurilennna sheath of
the auditory nerve.
 
(8) The cytoplasm of the auditory syncytium is undifferentiated during
the early stages. This represents the nascent or achromatic phase of the
auditory nerve axons.
 
(9) This material becomes fibrillated longitudinally in a definite manner
to form one continuous tract of neuro-fibrillae uniting the neuro-epithelium
with the cells in the hind brain. This represents the mature or chromatised
phase of the auditory nerve axons.
 
(10) The latter are thus not unicellular but multicellular in origin.
 
(11) Each axon is probably represented at first by a single fibrilla. The
unit of nerve structure is therefore 11ot the axon but the fibrilla. ’
 
(12) Those portions of the auditory syncytium next to the hind brain
Development of the Auditory Nerve in Vertebrates 131
 
a11d the otic vesicle become deprived of ,8-neuroblasts, and as a result there
is no development of a neurilemma sheath at these points. The latter
obviously represent sources of Weakness, at which toxins may readily find
an entrance, as already shown by Orr and Rows.
 
(13) The intimate association which the end organ bears to the hind
brain during the early stages through the medium of the auditory syncytium
never really becomes severed. We have therefore decided to abandon the
idea of contiguity by synapse in favour of a direct anatomical continuity of
the peripheral auditory tract.
 
ADDENDUM.
 
Since the above was written We have received a printed notice of the
forthcoming publication of a book by Professor Hans Held on Die
Eiitwic/colmig dos Ncrveizgewebes bei den Wii°b(%ltioi"en. This circular is
very brief, but is sufficient to enable us to gather that Held’s conclusions
are entirely in favour of the multicellular theory of neurogenesis. The
concluding words are very significant: “Nicht als eine Summe von
Neuronen (VValdeyer), den ‘anatomisch wie genetisch getrennten N erveneinheiten,’ ist das Nervensystem entwickelt Worden, sondern als ein
Neurencytium.” Held has adopted the Word nearenoytimn to denote the
nucleated mass of cytoplasm to which we have applied the term synoytium,
and has emphasised the importance of recognising this critical phase of
nerve formation. We are glad to observe that our results on nerve
histogenesis as studied in the auditory nerve are confirmed by the contemporaneous Work of Held.
 
LITERATURE.
 
(1) APATHY, ST v., “Ueber das leitende Element des N ervensystems und seine
Lagebeziehungen zu den Zellen bei Wirbeltieren und VVirbellosen,” Oompte-Ronda des
Séances du t2'oi.si£'7ne Oongrés international ole Zoolog-ie, Leyden, 1895.
 
(2) “Das leitende Element des Nervensystems und seine topographischen
Beziehungen zu den Zellen,” Mitteilangen der zoolog. Station zu Neapel, Bd. xii., 1897.
 
(3) BERNARD, H. M., “ Studies in the Retina,” Quart. Jour. Mic«2'. Sci, vol.
xlvii., 1903.
 
(4) BETHE, ALBR., “Ueber die Neurofibrillen in den Ganglicnzellen von Wirbeltieren, und ihre Beziehungen zu den Golgi-netzen,” Archiv fiir micros. 4nat,, Bd.
IV., 1900.
 
(5) —— Allgemeine Anatomic and Physiologic des Nerveizsystems, Leipzig, 1903.
Also papers in Archiv fiir Psychiatric, Bd. xxxiv., 1901, and in Neurolog. Centralbtatt, Jan. 1902.
 
(6) CAMERON, J ., and MILLIGAN, WM., “The Mode of Continuity of the Auditory
Sense-epithelium with the Nuclei in the Hind Brain,” Trans. Otolog. Society, 1906.
132 Development of the Auditory Nerve in Vertebrates
 
(7) CAMERON, J., and MILLIGAN, WM., “The Development of the Retina in
Amphibia: an Embryological and Cytological Study,” in three parts, Jour. Anat.
and Phys., vol. xxxix., 1905.
 
(8) —- “The Development of the Optic Nerve in Amphibians,” Studies from
the Anat. Department of the Urziverstty of Manchester, vol. iii., 1906.
 
(9) “The Development of the Vertebrate N erve-cell : a Cytological Study
of the N euroblast-nucleus,” Brain, 1906.
 
(10) “The Histogenesis of Nerve fibres : a Cytological Study of the
Embryonic Cell—nucleus,” Jour. Anat. and Phys., vol. xli., 1906.
 
(ll) FRAGNITO, 0., “ Su la Genesi del Prolungamenti protoplasmatici della
Cellula nervosa,” Anual. dz’ Nevr0l0g., anno xxii., f. 4.
 
(12) HIS, WM., (J r.), “ Zur Entwickelungsgeschichte des Acustico-facialis
Gehietes beim 1VIenschen,” Arch. fiir Anat. and Phys., Anat. Abtlr, 1899, Supp. Bd.
 
(13) KATZ, L. , “Ueber die Endigung des Nervus Cochleae im Corti’schen Organ,”
Zeitseh. f. 0/zrenhez'llt., Bd. xxix., 1889-90.
 
(14) KERR, J . GRAHAM, “On Some Points in the Early Development of Motor
Nerve Trunks and Myotomes in Lepiuloszren paradozca,” Trans. Roy. Soc. Edz'n.,
 
ivol. xli., 1904.
 
(15) LENHoss1~':K, M. VON, “Die Nervendigungen im Gehrirorgan,” Anat. Anz.,
Bd. viii., 1893.
 
(16) ——— “Die Nervendigungen in den Maculae und. Cristae acusticae,” Anat.
Hefte, ix., 1893.
 
(17) LILLIE, F. R, The Development of the Olztclc, New York, 1908.
 
(18) ORR, 1)., and Rows, R. G., “A Clinical and Experimental Investigation into
the Lymphogenous Origin of Toxic Infection of the Central Nervous System, Rev.
Near. and Psg/ch., May 1907.
 
(19) RErz1Us, G., Das G'eh0'r0rgan der Wz'rbeltz'ere, Stockholm, 1884. Also in
Btolog. Untcrsnrh, Bd. iii. and v., 1892, 1893.
 
('20) SCHULTZE, O., “Nachtrag zu meinem auf der Anatomen Versammlung in
Jena gehaltenen Vortrag iiber die Entwickelung des peripheren Nervensystems,”
Anat. Anz., Bd. xxv., 1904.
 
(21) SEDGWICK, A., “On the Cellular Theory of Development,” Quart. Joztr.
 
Micr. Sci, vol. xxxvii., 1895.
('22) STREETER, G. L., “ On the Development of the Membranous Labyrinth and the Acoustic and Facial Nerves in the Human Embryo,” Amer. Jour. of Anat.,
vol. vi., No. '2.
 
 
{{Footer}}
[[Category:Historic Embryology]][[Category:1910's]][[Category:Hearing]][[Category:Neural]][[Category:Draft]]

Latest revision as of 09:34, 15 August 2020

Redirect to:

Retrieved from ‘https://embryology.med.unsw.edu.au/embryology/index.php?title=Paper_-_The_development_of_the_auditory_nerve_in_vertebrates&oldid=418228’
Powered by MediaWiki