/ . Embryol. exp. Morph. Vol. 49, pp. 259-276, 1979
Printed in Great Britain © Company of Biologists Limited 1979
259
A study of digit fusion in the mouse embryo
By ELAINE MACONNACHIE
From the Department of Anatomy and Embryology, University College London
SUMMARY
During the embryonic development of the mouse limb separation of the digits is followed
by their union. This is a true, though temporary, epithelial fusion, a fused layer of epidermal
cells remaining intact until separation takes place after birth. The periderm cells in the line of
fusion are displaced to the dorsal or ventral surface of the foot. On the dorsal surface ^these
displaced cells form a prominent interdigital ridge of elongated, intertwined cells which
remains until the periderm is shed. During the fusion of the eyelids, and also of the pinnae to
the scalp, a similar ridge of periderm cells is formed.
INTRODUCTION
The mammalian foot appears first when the rounded footplate becomes
distinct from the rest of the limb. A combination of interdigital degeneration
and distal growth brings about the separation of the digits. In the mouse this
separation is followed by a temporary fusion which persists until after birth.
This is an uncommon feature of mammalian development though other instances
of temporary epithelial fusion do occur during the development of mammals,
including man. These include the union of prepuce and glans penis, the closure
of the eyelids and the fusion of the pinnae to the scalp (Burrows, 1944). It was
Burrows (1944) who showed that in all these cases, and in rat and mouse digit
fusion, an intact epithelial layer remained until separation took place. This was
brought about by differentiation in the form of keratinization. Eyelid fusion and
disjunction had previously been described by Addison & How (1921) and more
recently Andersen, Ehlers, Matthiessen & Claesson (1967) have shown that
a true epithelial fusion involving desmosomes occurs between the eyelids of
human embryos.
In the present work the surface changes taking place before and during mouse
digit fusion were studied by scanning electron microscopy. Light and transmission electron microscopy helped with the interpretation of the alterations
observed. Comparison was made with the process of fusion of the eyelids and
of the pinnae to the scalp, both of which take place at the same time as that of
the digits. Previous scanning electron microscope studies of secondary palate
formation in mouse and man (Waterman, Ross & Meller, 1973; Waterman &
Meller, 1974), in which permanent epithelial fusion takes place, have shown
that alterations, including cell death and desquamation, occur along the line of
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E. MACONNACHIE
presumptive fusion before contact between the palatal shelves is made. Changes
occurring in the region of fusion of mouse digits involve an interesting differentiation of periderm cells but cell death appears to be unimportant.
MATERIALS AND METHODS
BKW/TO mice were killed by cervical dislocation 15-18 days post coitum.
The embryos were removed from their membranes and fixed in 3 % glutaraldehyde in 0-15 M sodium cacodylate buffer, pH 7-2, for from one day to several
months.
The forefeet described in this study were selected from those which had been
used to measure volume changes taking place during preparation for scanning
electron microscopy. This work, which is reported elsewhere (Boyde, Bailey,
Jones, & Tamarin, 1977), compares the effects of different dehydration and
drying procedures. Over 200 mouse limbs were measured and investigated in
the scanning electron microscope, examples from each stage being selected for
light and transmission electron microscopy.
Scanning electron microscopy (SEM)
Forefeet were cut off at wrist level after fixation and rinsed in buffer. For
critical point drying they were dehydrated through a graded series of either
ethanol or acetone. Those in ethanol were then placed either in amyl acetate or
Freon 113, as an intermediate fluid, before drying from CO2 in a Polaron
critical point drying apparatus. The samples in acetone went straight into liquid
CO2. For freeze drying the feet were rinsed in buffer and then transferred to
a chloroform and water mixture. After rapid freezing in Freon 12 at —155 °C
followed by liquid nitrogen at -196°C, they were placed, in an Edwards
Speedivac-Pearse Tissue Dryer Mk 1 at - 70 °C. After at least 2 days they were
slowly brought up to room temperature.
Heads were removed from fixed embryos, cut sagittally, dehydrated through
a graded ethanol series and placed in Freon 113. After critical point drying they
were mounted on aluminium stubs with Bostik Quick Set adhesive and coated
with gold in a Polaron sputter coater. The dried feet were similarly mounted
and coated. All specimens were studied in a Cambridge Stereoscan S4-10
operated at 10 kV and photographed on Ilford FP4 35 mm film.
Transmission electron microscopy (TEM)
After rinsing in 0-15 M sodium cacodylate buffer, the fixed feet were postfixed in 1 % OsO4 in the same buffer for 1 h, then rinsed and dehydrated
through a graded ethanol series. From ethanol they were transferred to epoxy
propane and embedded in Araldite. Eyes and ears were removed and treated in
the same way. Sections cut on a Huxley ultramicrotome were stained with
uranyl acetate and lead citrate and examined in a Philips 300 microscope.
Study of digit fusion in the mouse
embryo
261
Table 1. Features offorelimb development
Stage
Characteristics
Gestation Time
(Griineberg 1943)
Distinct
.footplate
11 days
Slight
indentation
12 days
Clear
indentation'
13 days
Digits start
to separate
"*
14 days
Continuation
of separation
Digits separate
and widely spread
Fusion begins at
base of digits
Fusion continues
along the digits
10
15 days
"*
16 days
Digits fused, all
surface wrinkled
17 days.
Periderm shed,
digits stay fused
until after birth
18/19 days
For light microscopy (LM) 1 jum thick sections were taken and stained with
toluidine blue.
OBSERVATIONS
Mouse embryos were staged according to their forelimb development, starting
from the appearance of a distinct footplate. Hind-limbs follow the same course
of development, beginning about 24 h later. Approximate ages of gestation are
given according to Griineberg (1943), recently confirmed by Wahlsten &
Wainwright (1977), though by 14 days up to 12 h variation within a single litter
may be found, as has been reported in the rat (Burlinghame & Long, 1939).
The stages of interest in the present study are those from stage 6 onwards, that
is, after the initial separation of the digits (Table 1).
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E. MACONNACHIE
Study of digit fusion in the mouse embryo
263
Limb development
Stage 6 (15 days)
At this stage separation of the digits is complete and they are widely spread
(Fig. 1). The surface of the foot is covered with a single layer of periderm cells
which are thinly spread with short microvilli projecting from the surface,
particularly along the cell boundaries (Fig. 2). Beneath the periderm the
epidermis consists of basal and intermediate layers. Many desmosomes and small
intercellular spaces occur between the periderm and epidermis, whilst much larger
spaces are found amongst the epidermal cells.
At the junction of two digits a few cells can be seen which are different in
shape and surface features from the rest of the periderm: they are typically more
compact and often elongated. Their surface projections are more numerous and
include blebs and ridge or flap-like extensions, as well as microvilli (Fig. 3). The
elongated cells may be oriented in a dorso-ventral direction down the lateral
walls of the digits or may form a string of cells across the back of the groove
between the digits.
This differentiation of periderm cells takes place at the junction of the third
and fourth digits slightly ahead of that between the other digits and it is here
that a ridge of cells is first seen. Viewed from the dorsal surface of the foot the
ridge extends ventrally from the differentiating cells at the base of the digits
(Fig. 4). The cells in the ridge are elongated and closely joined together (Fig. 5),
their surfaces showing the variety of projections found on the differentiating
periderm cells.
Stage 7 (15 days)
Fusion of the digits begins during this stage. On the dorsal surface this is
indicated by the extension distally, parallel with the digits, of ridges of cells
seen forming at the end of stage 6. Such a ridge now passes forward between the
digits and then turns down towards the ventral surface (Fig. 6). The cells in the
ridge are elongated and closely intertwined, their surfaces covered with ridge-like
FIGURES
1-6
Fig. 1. Stage-6 forelimb showing the dorsal surface. SEM. Field width 1-47 mm.
Fig. 2. Periderm cells on the dorsal surface of the forelimb at stage 6. SEM. Field
width 40 /tm.
Fig. 3. Differentiating periderm cells at the junction of two digits. Stage 6. SEM.
Field width 41 /*m.
Fig. 4. Part of the dorsal surface of a forelimb showing the junction of the third and
fourth digits. A ridge of cells is indicated (arrow) passing down towards the ventral
surface. Stage 6. SEM. Field width 416 (im.
Fig. 5. Cells in an early ridge, similar to that seen in Fig. 4. Stage 6. SEM. Field
width 11 /tm.
Fig. 6. Part of two digits at stage 7 showing the dorsal interdigital ridge extending
between them. SEM. Field width 406/tm.
264
E. MACONNACHIE
7
F I G U R E S 7 AND 8
Fig. 7. Stereo pair of part of the surface of a cell in the interdigital ridge showing the
tendency to longitudinal alignment of the surface projections. Stage 7. SEM. Field
height 8-3 ju,m.
Fig. 8. Section, at right angles to the longitudinal axis of the digits, of part of an
interdigital ridge with similarly differentiated periderm cells to either side. Stage 7.
TEM. Field width 14 fim.
Study of digit fusion in the mouse embryo
265
extensions and microvilli which tend to be aligned with the longitudinal axis of
the cells (Fig. 7). Some cells also have small blebs. Lateral to the ridge are
similar, but less elongated, cells, some of which join the ridge.
A transverse section through the ridge shows that, although the cells are
tightly joined around the external surface, internally large intercellular spaces
are present (Fig. 8). These occur because the cells are joined by desmosomes
between narrow cytoplasmic extensions leaving large spaces. The cells have
large nuclei and dense cytoplasm with many free ribosomes and small areas of
rough endoplasmic reticulum. Mitochondria are dispersed throughout the
cytoplasm and bundles of microfilaments are present in some cells. There are
many long microvillous-like extensions, or sections through the ridges seen in
SEM, on the outer surface, close to which small vesicles can be found.
Differentiating periderm cells are found just distal to the end of the ridge, on
the lateral walls of the digits. These are similar to those seen at the junction of
the digits at stage 6, being more rounded and having more surface projections
than the rest of the periderm. Fig. 9 shows a section close to the end of the ridge
where it passes down between the digits. Here cells of the ridge can be seen
adjoining the differentiated periderm cells of one digit. In the TEM, desmosomes
are found between these cells, often on microvillous extensions. On the other
digit similarly transformed preiderm cells lie very close to those of the ridge.
The intermediate layer of the epidermis adjacent to the interdigital ridge is
broader than that around the remainder of the digit, the cells being more
widely separated.
A section taken proximal to this (Fig. 10) shows the two digits joined towards
the dorsal surface. In the centre of the junction is an irregular band of periderm
with the interdigital ridge extending dorsally and a smaller line of cells ventrally.
More proximal still (Fig. 11), the digits are joined over a wider area but the
periderm is no longer present in the line of fusion. The cells of the intermediate
layers of the two digits are now united, though with large intercellular spaces.
The periderm cells are on the external surfaces only, the dorsal interdigital
ridge and associated cells lying at one end of the fused epidermis and a smaller
group extending ventrally.
As fusion of the epidermal layers continues in a ventral direction the periderm
cells remaining on the lateral walls of the digits join those displaced earlier.
When fusion is complete these cells can be seen lying in a groove between two
digits on the ventral surface. They are elongated and intertwined like those of
the dorsal ridge (Fig. 12), but less prominent. The fused epidermis now consists
of a central intermediate layer two or three cells thick, except close to the dorsal
surface where it is wider, with a basal layer on either side each limited by
a basement lamina (Fig. 13). All the cells contain large amounts of glycogen,
as do other epidermal cells at this stage, in contrast to those of the periderm which
do not. Very few tonofilaments are found in the fused epidermal layer compared
with other parts of the epidermis.
E. MACONNACHIE
FIGURES
9-12
Figs. 9-11. A series of sections, taken at right angles to the long axis of the foot,
through a region where fusion between two digits is taking place. P, Periderm; R,
dorsal interdigital ridge; E, epidermis; I, intermediate epidermal layer; B, basal
epidermal layer. Stage 7. LM. Field width 224 /*m.
Fig. 12. A dorsal interdigital ridge extending down from the base of the digits.
Stage 8. SEM. Field width 82 /tm.
Study of digit fusion in the mouse embryo
267
Fig. 13. Section through the fused epidermal layer between two digits. Arrows
indicate the basement laminae. G, Glycogen. Stage 7. TEM. Field width 24/mi.
268
E. MACONNACHIE
Darkly staining bundles of tonofilaments are not seen in the periderm cells
though more diffuse bundles of filaments do occur. In the elongated periderm
cells forming the interdigital ridge these bundles tend to be aligned with the
long axes of the cells. Microtubules are often found in a similar orientation.
Stage 8 (16 days)
Fusion proceeds along the digits which come to lie parallel to each other
(Fig. 14). The position of the nailplate becomes more clearly marked at this
stage. As the interdigital ridge extends along the length of the digits the cells in
it become more elongated. The surface of the foot begins to wrinkle due to
variations in thickness of the epidermis at this stage, the wrinkles starting
proximally and spreading out towards the digits. The periderm cells covering
the foot become thinner and have fewer surface projections.
Along the second digit, on the side next to the first, a line of elongated cells
is found which is similar in appearance to those associated with digit fusion
(Fig. 15). The first digit is much reduced in length, being little more than a nailplate, so fusion between this and the second is possible only for a very short
distance.
Stage 9(17 days)
As at the end of stage 8 the digits are joined throughout their length and
lying over the lines of fusion are the interdigital ridges. The cells in the ridges
become more elongated and narrower with the growth of the foot and their
surface appears smoother with deep indentations (Fig. 16). Seen in transverse
section they are more closely joined than at stage 7, having much less intercellular space (Fig. 17). Considerable interdigitation is found, not only between
these cells but also between the ordinary periderm cells. Around the periphery
of the ridge, and near the external surfaces of the similar cells at its base, large
vesicles are found associated with narrow projections. Many of these projections
appear bifurcated in cross-section.
The outer epidermal layers become the stratum granulosum at this stage with
the presence of keratohyalin granules. These granules are of irregular shape,
especially in the outermost layer, and often have lipid-like bodies associated
with them; they appear similar to those described in the rat embryo (Bonneville,
1968). The epidermal cells are flattened and between the outer two or three
layers, and next to the periderm, the intercellular space has a vesicular appearance and there are few junctions between the cells.
The surface of the entire foot now has a wrinkled appearance. The periderm
cells are very thinly spread, still with clearly marked boundaries but with fewer
projections which now consist of small ridges and blebs. Because the periderm
cells are so thin, bulges formed by the keratohyalin granules in the outer
epidermal layer can be seen on the surface (Fig. 18). The fused epidermal layer
Study of digit fusion in the mouse embryo
269
14
FIGURES
14-17
Fig. 14. Dorsal surface of a late stage 8 forefoot. SEM. Field width 1-6 mm.
Fig. 15. Lateral wall of a second digit, with the first in the foreground, along which
a line of differentiated cells can be seen. Stage 8. SEM. Field width 379 /on.
Fig. 16. Surface of the dorsal interdigital ridge at stage 9. SEM. Field width 15 /J-VCV.
Fig. 17. Transverse section through a dorsal ridge and underlying epidermis.
Keratohyalin granules can be seen in the outer flattened epidermal layers. Stage 9.
TEM. Field width 15 /on.
18
EMB 49
270
E. MACONNACHIE
between the digits is the same width as at stage 7 but tonofilaments are now
more common.
Stage 10 (18+ days)
The periderm, including the interdigital ridges, has been shed. The surface
of the foot is very wrinkled with many keratohyalin granules prominent
(Fig. 19). The digits are still fused and remain so until about 6 days after birth.
Eyelids
During the 15th day of gestation the eyelids develop by growing out towards
each other and when they meet fusion occurs, beginning at the ends and continuing towards the centre of the eye. The process of union is similar to that
occurring between the digits, the periderm cells join and then are displaced to
the outer surface as the epidermal layers fuse. The fused epidermal layer between
two basement laminae remains until separation takes place after birth.
During the development and fusion of the eyelids the periderm cells are
elongated, radiating out from the growing edges (Fig. 20). By the 17th day,
when fusion is complete, elongated cells remain only over the line of union
while the cells on the surface of the eyelids are flattened and polygonal, like
those on the rest of the face. The elongated periderm cells form an interwoven
ridge similar to the dorsal interdigital ridge, though broader, especially over
the centre of the eye (Fig. 21). Periderm is not found on the inner, conjunctival
side of the eyelids.
FIGURES
18-23
Fig. 18. Part of the surface of a forefoot at stage 9 showing the unevenness. Bulges
due to the keratohyalin granules in the outer epidermal layer can be seen through
the very thin periderm cells. SEM. Field width 80 fim.
Fig. 19. Surface of the foot after the periderm has been shed, the epidermal cells are
very wrinkled and many keratohyalin granules are present. Stage 10. SEM. Field
width 81 fim.
Fig. 20. Elongated periderm cells over the line of eyelid fusion and radiating out
from the growing edge. The centre of the eye is below the lower left corner. SEM.
Field width 162 fim.
Fig. 21. Completely fused eyelids with a ridge of periderm cells over the line of
union. SEM. Field width 1-43 mm.
Fig. 22. Pinna folded forward with a ridge of periderm cells around the line of
fusion. SEM. Field width 1-47 mm.
Fig. 23. Elongated interwoven periderm cells lying over the line of fusion of the
pinna. SEM. Field width 98 fim.
Study of digit fusion in the mouse embryo
271
18-2
272
E. MACONNACHIE
Pinnae
At the time that the eyelids are developing, the pinnae of the ears are growing
and they too become temporarily fused - to the scalp (Fig. 22). They lie
forward, over the external auditory meatus, and a ridge of elongated intertwined cells is found around the line of fusion (Fig. 23). Fusion begins at the
ends and extends towards the centre where, as with the eyelids, the ridge is
broader. Disjunction takes place after birth.
DISCUSSION
This study has shown that the fusion of mouse digits involves the formation
of prominent dorsal interdigital ridges consisting of tightly interwoven elongated
cells. These cells are differentiated periderm cells which have been displaced
from the lateral walls of adjacent digits. Less prominent, but similar, ridges are
formed on the ventral surface and all remain until the periderm is shed. Similar
lines of periderm cells are found over the line of fusion of the eyelids and around
the fused pinnae. These are three examples of temporary epithelial fusion,
a layer of epidermal cells remaining intact until keratinization brings about
separation after birth. Desmosomes are found between the cells in the centre
of the united epithelium and they were reported by Andersen et al. (1967) in
fused human eyelids to show that a definite union, not merely adhesion, had
taken place.
Little work has been reported on temporary epithelial unions, though, unlike
digit fusion, that of the eyelids and pinna is commonly found during the
development of mammals, including man (Burrows, 1944). In describing the
development of rat eyelids, Addison & How (1921) showed that fusion took
place soon after their first appearance. The epithelial cells of both eyelids grew
out rapidly, ahead of the mesenchyme, towards each other. These authors
suggested that, after the epithelial layers met, the pressure of the still growing
mesenchyme pushed them together causing some cells to be squeezed out.
During the process of digit fusion cells are similarly 'pushed out' to one or
other side of the united epithelium. These cells were found to be peridermal in
origin, as were those forming the ridges along the lines of fusion of mouse
eyelids and pinnae.
The periderm is a single layer of cells covering the outer surface of mammalian embryos for part of their development. It is shed when keratinization
of the epidermis takes place but is never keratinized itself. The complexity of
its development varies, possibly with the length of time of its existence. That of
the rat develops microvilli on its surface but remains as a thin flattened layer
(Bonneville, 1968), while on the human embryo, first simple, then complex
blebs form after microvilli (Wolf, 1967a, b; Hoyes, 1968; Holbrook & Odland,
1975). The periderm of the rat persists for only about 9 days (Bonneville, 1968)
whilst that of man for over 100 days (Holbrook & Odland, 1975).
Study of digit fusion in the mouse embryo
273
Over the mouse foot the periderm develops much as that described on the
surface of the rat embryo (Bonneville, 1968), but, when the digits have separated,
cells near their base differentiate to become compact and elongated. It is these
cells which are displaced, as fusion between the digits proceeds, and form the
interdigital ridges. Degenerating periderm cells were rarely found in the line
of fusion so it appears that they all move, or are pushed, out of the way of the
fusing epidermal layers. The change in shape from flattened epithelioid to
compact and elongated suggests that these periderm cells may actively migrate.
Most evidence concerning the relationship between cell shape and locomotion
has come from in vitro observations. Fibroblasts, which migrate if a suitable
substrate is available, are elongated and if prevented from elongating do not
move (Vasiliev et al. 1970). Epithelial cells, which are rounded or polygonal in
outline, though capable of some slight movement when joined as a sheet, do not
migrate individually (Middleton, 1973; DiPasquale, 1975). A recent in vivo
study of wound healing has demonstrated that the migrating epithelial cells are
elongated (Repesh & Oberpriller, 1978), as are cells migrating during early
embryogenesis in the chick (Bancroft & Bellairs, 1975).
As the digits come to lie parallel to each other the fused epidermal layer
becomes narrower, due to the reduction in the amount of intercellular space
when the digits draw close together. The pressure exerted here may also be
pushing the differentiated periderm cells along in front of the fusing epidermis.
On the dorsal surface the cells remain tightly joined together in the form of
a ridge and become more elongated as the digits grow in length. Ventrally, the
displaced periderm cells are in a depression between two digits as fusion does
not extend quite level with the ventral surface of the foot. From their first
appearance in the dorsal ridge the cells have many surface projections and small
pinocytotic vesicles can be seen. Later, when fusion is complete along the length
of the digits, these cells appear to be actively taking in droplets of amniotic
fluid. It has been suggested that human periderm may be important in absorbing
glucose from the amniotic fluid and storing it as glycogen, particularly at the
time of microvillous and bleb formation (Holbrook & Odland, 1975; Verma,
Varma & Dayal, 1976). (Though Wolf (19676) and Hoyes (1968) believe that
it may discharge droplets into the amniotic fluid.) Mouse, like rat (Bonneville,
1968), periderm does not store glycogen but could be absorbing and using
glucose. At this time keratinization has begun in the outer epidermal layers
with the appearance of unusual keratohyalin granules associated with lipid-like
droplets, similar to those described in the rat (Bonneville, 1968). Also, although
the periderm cells are joined by interdigitations and desmosomes, junctions
with the underlying epidermal cells have become reduced in number and the
intercellular space vesicular in appearance. These changes may restrict the
passage of food to the periderm cells obliging them to make up the loss from the
amniotic fluid. The cells of the dorsal ridge, apart from being further away from
whatever food was available, have a smaller external surface area than the
274
E. MACONNACHIE
thinly spread periderm and might therefore be expected to show more engulfing
activity.
An example of permanent epithelial fusion occurs during the formation of
the secondary palate. Here the fused epithelium of the palatal shelves is invaded
by mesenchyme, occasionally leaving small 'pearls' of epithelial cells. It was
suggested that the loss of lamellation gave rise to mesenchymal invasion
(Barry, 1961) and Farbman (1968) reported that in the mouse the basement
laminae on the opposing shelves were interrupted before fusion occurred.
Andersen, Ehlers & Matthiessen (1965) described a thickening of the basement
laminae of human eyelids, which began before fusion, and suggested that this
prevented the penetration of mesenchymal cells. The basement laminae of the
fused epithelium of mouse digits remain intact but do not appear to thicken.
It is interesting to compare the surface changes taking place on the palatal
shelves before and during fusion with those on the mouse digits. Changes in
the morphology of cells along the margins of the palatal shelves before contact
had been made were reported in mouse (Waterman et al. 1973) and man
(Waterman & Meller, 1974). In man the alterations included the elongation and
intertwining of cells similar to those found on mouse digits, though randomly
oriented, but this did not occur on the mouse palate. Cell death and desquamation were other changes seen on human palate, and degeneration of superficial cells has been found in hamster palate prior to fusion (Chaudhry & Shah,
1973). This does not seem to play a role in digit fusion. Although elongation
and intertwining of cells occurs along human palatal shelves before fusion, the
cells which actually fuse are less rounded, being flat (Waterman & Meller, 1974)
and no ridge of cells is formed over the line of fusion, except on the nasal surface
of the soft palate. However, as the surface cells of the human oral cavity do not
develop in the same way as the periderm over the rest of the body, Whittaker &
Adams (1971) suggested that they should not be called peridermal.
Burrows (1944) thought that if undifferentiated epithelial cells were kept in
contact the layers would fuse. The changes occurring on the lateral walls of the
digits, before contact between two is made, suggest that some predetermination
is involved, as in the case of permanent palatal fusion. The development of
a line of differentiated periderm cells along the side of the second digit next to
the first is interesting as fusion between the two is only possible over a very short
distance, due to the reduced length of the first digit. Perhaps merely the presence
of a digit, however small, or the beginning of fusion at the base, induces
prefusion differentiation to occur.
It is not hard to imagine that the fused eyelids protect the eye during its later
development and, similarly, that the pinnae afford protection to the developing
ear, but the purpose of digit fusion is less easy to fathom. It does seem, however,
to be related to the degree of development attained at birth. Those rodents
which are known to have fused digits at birth, together with closed eyes and
ears, have very short gestation periods and belong to the suborder Myomorpha.
Study of digit fusion in the mouse embryo
275
Though the Sciuromorpha are also born poorly developed I can find no reference to the state of their digits. However the third suborder, the Hystricomorpha,
differ from the other two in having long gestation times and being born as
miniature adults. Their digits are not fused at birth nor it is believed during
their development (I. W. Rowlands, personal communication), as is the case
with most other mammals. (It should be noted that in animals with webbed
feet the webbing is due to lack of initial separation of digits, caused by either
a complete lack, or reduction in the extent, of interdigital degeneration (Fallon
& Cameron, 1977).) Burrows (1944) showed that the separation of prepuce and
glans penis was under hormonal control and suggested that other temporary
unions may be similarly controlled. Though this has not yet been demonstrated,
if it were the case the immaturity of such a system may explain why animals born
in a poorly developed condition still have such unions intact. It does not, of
course, explain why digit fusion occurs only in such animals.
I should like to thank Doctors A. Boyde and S. J. Jones and Professors E. J. Reith and
A. Tamarin for their encouragement and criticism. This work received indirect support
from MRC grants to Dr A. Boyde.
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(Received 2 August 1978, revised 19 September 1978)