Mouse embryos can be staged according to a variety of criteria,
the most general of which are those described by Theiler in "The House
Mouse: Atlas of Mouse Development" (Springer-Verlag, New York, 1989).
Theiler's criteria are too broad to distinguish many of the important phases
of early development and must therefore be supplemented by others, for example,
cell number, somite number or those charcteristics used by Downs and Davies
(1993) Development, 118, 1255. We have therefore combined these different
criteria in the table1 below which defines a new set of stages
based on the numbered Theiler series, but with intermediate divisions indicated
by non-integer stage numbers. Embryos of the same gestational age
may differ in their stage of development. We have therefore included
in the table an indication of the expected range of gestational ages (days
of gestation, dpc) over which each developmental stage may be found. Different
mouse strains develop at different rates and, in some cases show differences
in the relative rates of development of different organs. Strictly, the
stages recognised by Downs and Davies apply to outbred mice of the PO strain.
The data in the remainder of the table below refer to embryos of crosses
between F1 hybrid (C57BL X CBA) mice.
Each Theiler stage is linked (click on the number) to its corresponding
diagram, with more details of the defining features for that stage. A
brief text or pictorial index
to the diagrams is also provided.
|
Theiler Stage |
dpc (range)2 |
Somite
No.3 |
Cell number |
(C57BLxCBA)F1 mice4 |
PO mice5 |
|
1 |
0-0.9
(0 -2.5) |
|
1 |
One-cell egg |
|
|
2 |
1
(1 -2.5) |
|
2-4 |
Dividing egg |
|
|
3 |
2
(1-3.5) |
|
4-16 |
Morula |
|
|
4 |
3
(2-4) |
|
16-40 |
Blastocyst, Inner cell mass apparent |
|
|
5 |
4
(3-5.5) |
|
|
Blastocyst (zona-free) |
|
|
6 |
4.5
(4-5.5) |
|
|
Attachment of blastocyst, primary endoderm covers
blastocoelic surface of inner cell mass |
|
|
7 |
5
(4.5-6) |
|
|
Implantation and formation of egg cylinder Ectoplacental
cone appears, enlarged epiblast, primary endoderm lines mural trophectoderm |
|
|
8 |
6
(5-6.5) |
|
|
Differentiation of egg cylinder. Implantation
sites 2x3mm. Ectoplacental cone region invaded by maternal blood,
Reichert's membrane and proamniotic cavity form |
|
|
9a
|
6.5
(6.25-7.25)
|
|
|
Pre-streak (PS), advanced endometrial
reaction, ectoplacental cone invaded by blood, extraembryonic ectoderm,
embryonic axis visible, |
PS |
|
9b
|
|
|
|
Early streak (ES), gastrulation starts,
first evidence of mesoderm |
ES |
|
10a
|
7
(6.5-7.75) |
|
|
Mid streak (MS), amniotic fold starts to form |
MS |
|
10b
|
|
|
|
Late streak, no bud (LSOB), exocoelom |
LS |
|
10c
|
|
|
|
Late streak, early bud (LSEB), allantoic bud
first appears, node, amnion closing |
|
|
11a
|
7.5
(7.25-8) |
|
|
Neural plate (NP), head process developing, amnion
complete |
OB |
|
11b
|
|
|
|
Late neural plate (LNP), elongated allantoic
bud |
EB/ LB |
|
11c
|
|
|
|
Early head fold (EHF) |
EHF |
|
11d
|
|
|
|
Late head fold (LHF), foregut invagination |
LHF |
|
12a
|
8
(7.5-8.75 ) |
1-4 |
|
1-4 somites, allantois extends, 1st branchial
arch, heart starts to form, foregut pocket visible, preotic sulcus
(at 2-3 somite stage) |
|
|
12b
|
|
5-7 |
|
5-7 somites, allantois contacts chorion at the
end of TS12
Absent 2nd arch, >7 somites |
|
|
13 |
8.5
(8-9.25) |
8-12 |
|
Turning of the embryo, 1st branchial arch has
maxillary and mandibular components, 2nd arch present
Absent
3rd branchial arch |
|
|
14 |
9
(8.5-9.75) |
13-20 |
|
Formation & closure of ant. neuropore, otic
pit indented but not closed, 3rd branchial arch visible
Absent forelimb bud |
|
|
15 |
9.5
(9-10.25) |
21-29 |
|
Formation of post. neuropore, forelimb bud, forebrain
vesicle subdivides
Absent hindlimb bud, Rathke's pouch |
|
|
16 |
10
(9.5-10.75) |
30-34 |
|
Posterior neuropore closes, Formation of hindlimb
& tail buds, lens plate, Rathke's pouch; the indented nasal processes
start to form
Absent thin & long tail |
|
|
17 |
10.5
(10-11.25) |
35-39 |
|
Deep lens indentation, adv. devel. of brain tube,
tail elongates and thins, umbilical hernia starts to form
Absent nasal pits |
|
|
18 |
11
(10.5-11.25) |
40-44 |
|
Closure of lens vesicle, nasal pits, cervical
somites no longer visible
Absent auditory hillocks,
anterior footplate |
|
|
19 |
11.5
(11-12.25) |
45-47 |
|
Lens vesicle completely separated from the surface
epithelium. Anterior, but no posterior, footplate. Auditory hillocks
first visible
Absent retinal pigmentation and sign
of fingers |
|
|
20 |
12
(11.5-13) |
48-51 |
|
Earliest sign of fingers (splayed-out), posterior
footplate apparent, retina pigmentation apparent, tongue well-defined,
brain vesicles clear
Absent 5 rows of whiskers, indented
anterior footplate |
|
|
21 |
13
(12.5-14) |
52-55 |
|
Anterior footplate indented, elbow and wrist
identifiable, 5 rows of whiskers, umbilical hernia now clearly apparent
Absent hair follicles, fingers separate distally |
|
|
22 |
14
(13.5-15) |
56-~ 60 |
|
Fingers separate distally, only indentations
between digits of the posterior footplate, long bones of limbs present,
hair follicles in pectoral, pelvic and trunk regions
Absent
open eyelids, hair follicles in cephalic region |
|
|
23 |
15 |
|
|
Fingers & Toes separate, hair follicles also
in cephalic region but not at periphery of vibrissae, eyelids open
Absent nail primordia, fingers 2-5 parallel |
|
|
24 |
16 |
|
|
Reposition of umbilical hernia, eyelids closing,
fingers 2-5 are parallel, nail primordia visible on toes
Absent wrinkled skin, fingers & toes joined together |
|
|
25 |
17 |
|
|
Skin is wrinkled, eyelids are closed,umbilical
hernia is gone
Absent ear extending over auditory
meatus, long whiskers |
|
|
26 |
18 |
|
|
Long whiskers, eyes barely visible through closed
eyelids, ear covers auditory meatus |
|
|
27 |
19 |
|
|
Newborn Mouse |
|
|
28 |
|
|
|
Postnatal development |
|
- Bard, J.B.L., Kaufman, M.H., Dubreuil, C., Brune. R.M., Burger,
A., Baldock, R.A., Davidson, D.R. (1998). An internet-accessible database
of mouse developmental anatomy based on a systematic nomenclature. Mechanisms
of Development 74, 111-20.
- Days post conception, with the morning after the vaginal plug is
found being designated 0.5 dpc (or E0.5). For detailed discussion see
Kaufman (1994). The Atlas of Mouse Development (2nd printing),
pp. 515-525. London: Academic Press.
- The figure given refers to the number of the most caudal somite.
No account is taken of somites partitioning into dermomyotomes and sclerotomes,
nor of their subsequent differentiation.
- Adapted from Theiler (1989) [The House Mouse: Atlas of Embryonic
Development. New York: Springer-Verlag] and Kaufman (1994); detailed
staging for Theiler stages 9-12 courtesy of K. Lawson [personal communication].
- From Downes, K.M. and Davies, T. (1993). Staging of gastrulating
mouse embryos by morphological landmarks in the dissecting microscope.
Development, 118, 1255 - 1266.
Comments
General comment on timing (dpc): In judging the lower
and upper ranges of dpc equivalent to a particular Theiler stage, we have
generally followed Theiler's book and, in most cases, have given a wider
range than Theiler, because the numbers of embryos he cites are small.
We have given a larger range at the maximum than the minimum because,
in general, embryos are more likely to be retarded by their environment
or genetic constitution than made to proceed more quickly through development.
In most cases, however, the resulting dpc range is an estimate that is
consistent with the results of Theiler, but not based on additional evidence.
Comment on somite numbers: The range of somite numbers
for each stage is given only as a guide to what might be expected of typical
embryos. As can be seen from Theiler (1989)4 the true range
can be much wider. Therefore, for all stages after TS12, the somite number
should not be taken as a reliable global indicator of the overall embryo
stage.
Richard Baldock, Jonathan Bard, Duncan Davidson and Kirstie Lawson, 7th
May 1998
Please mail comments to Prof. Jonathan
Bard |
