Эктодермальные производные

Аденогипофиз

Эмалевый орган зуба

нормальный эпидермис
Не формируется нормальная дерма
Абдоминальная
эктодерма
+
мезодерма стопы
Эктодерма
дифференцируется как на стопе

Эктодерма стопы
+
мезодерма скальпа

Эктодерма
дифференцируется как на скальпе

которые экспрессируются в различных клеточных слоях эпидермиса
Под влиянием дифференцирующих сигналов

Notch1 индуцирует экспрессию ряда белков (involucrin, Keratin1 (K1), ингибитор клеточного цикла Cip1), и временно блокирует экспрессию других белков (fillagrin, loricrin) – их экспрессия происходит, только на последних стадиях дифференцировки (когда клетки эпидермиса смещаются в верхние слои).

Также Notch1 блокирует сигнальные пути Wnt (β-catenin-mediated Wnt signaling) и Shh (Gli2-mediated sonic hedgehog signaling). У мыши при блокировании экспрессии Notch1 в эпидермисе реактивируются каскады Wnt и Shh: в результате возникают опухоли (basal-cell-carcinoma-like tumours)

http://www.licr.org/C_news/newslink/0406/0406_Notch1.html

Дифференцировка клеток кожного эпидермиса (постнатальная)

is indicated by colors: adenohypophysal (brown), olfactory (yellow),

lens (green)
otic (red).

Litsiou et al., 2005

Стадия нервных валиков:
проспективные потенции эктодермы на границе с нейроэктодермой

Стадия перехода от нейральной пластинки к нервным валикам

Индуцирующие сигналы мезодермы
(головная мезенхима) определяют положение и спецификацию преплакодного участка эктодермы

placode
(A) The part of PPR shown here give rise

to the prospective lens ectoderm and may be already specified as a lens lineage. The optic sulci (OS) are morphologically distinct regions of the prospective forebrain. The precise contact between the optic vesicle with the surface ectoderm determines location of the lens placode. (B) The optic vesicle (OV) reaches the prospective lens ectoderm (PLE) and mesenchymal cells (Me) are excluded from the region of contact of OV and PLE (E9.5). The lens placode (LP) invaginates (iLP) and is engaged with the optic vesicle in a reciprocal process to form the lens vesicle and optic cup (OC).

SOX2 (Kamachi, et al., 1998; Kamachi, et al., 2001).
(Right)

Lens-specific δ1-crystallin expression is regulated by the enhancer in the third intron of the gene. The activity of this gene is dictated by the 30-bp DC5 region, which by itself shows a lens-specific enhancer activity when present as a multimeric form. The DC5 minimal enhancer is regulated by the cooperative action of Pax6 and SOX2, which bind next to each other at their respective sites in the DC5 sequence.
(Left) In the embryo, Pax6 is initially expressed broadly in the head ectoderm, and contact by the optic vesicle (retina primordium) at stage 11 induces SOX2 (and SOX3 in the chicken) in the same ectoderm (st. 12). This results in cooperative action of Pax6 and SOX2 at the target sites, and initiates lens development, as indicated by δ1-crystallin expression and lens placode morphogenesis.[Histological images are reproduced from Kamachi et al. (1998), Involvement of Sox1, 2 and 3 in the early adsubsequent molecular events of lens induction. Development 125, 2521-2532,

разных типах клеток, в зависимости от сопутствующей экспрессии факторов транскрипции

ЭСК и эпибласт

Нейроэктодерма

Хрусталик глаза

Во всех случаях работает комплекс из двух белков, взаимодействующий с расположенными в непосредственной близости последовательностями нуклеотидов

The primordium of the adenohypophysis (Rathke’s pouch in the mouse

and chicken) expresses Pax6 and SOX2.

In zebrafish mutants defective in shh
signaling, the hypophysis
primordium fails to express
hypophysis-proper transcription
factors, e.g., Lim1 and Nkx2.2, and
develops into lens (Kondoh, et al.,
2000; Varga, et al., 2001).

Zebrafish mutations in Gli-mediated
hedgehog signaling lead
to lens transdifferentiation from
the adenohypophysis anlage.






Mechanisms of Development 96, 165-174,

конечностей – Tbx-5
Почка нижних конечностей – Tbx-4

конечностей – Tbx-4
Tbx-5 (4)
FGF-8
FGF-8




FGF-10
мезодерма
эктодерма

на вентральной стороне
Формирование
антерио-постериальных
и
проксимально-дистальных
различий в почке

конечности:

of Wnts and frizzled receptors in stage 20 chick limb

buds.
Sketches of dorsal views showing the expression of
A) Wnt3a ,
B) Wnt5a ,
D) Fz3
E) Fz4 and
F) Fz10 .

C) is a sketch of a transverse section showing the expression of Wnt7a (purple) in the dorsal (d) ectoderm, with underlying mesenchymal expression of Lmx1 (yellow) and engrailed (green). in ventral (v) ectoderm

mouse embryos after 4OHTM injection at different stages during gestation

and recovery on different days of development, as indicated. The arrowhead (F) indicates lacZ-positive cells of an independent ectodermal clone.

Development 134, 3713-3722 (2007) doi:10.1242/dev.02873

Mouse strains
RERT and R26R or R26R-EYFP knock-in alleles were maintained in double homozygosity in a mixed genetic background, a condition that did not show
any obvious adverse phenotype. To generate experimental litters, males of the double-homozygous stock were mated with CD1 outbred females, so that all embryos from these crosses were double-heterozygous for the inducer and reporter alleles. To induce recombination, pregnant females from timed matings were injected intraperitoneally with 4-hydroxytamoxifen
(4OHTM) dissolved in corn oil at 0.5 mg/ml. lacZ staining [i.e. staining for -galactosidase (-gal) activity] was performed as previously described (Torres, 1998).

mouse limb development. Whole-mount in situ hybridization was used to

show the distribution of RNA for Bmp2, Bmp4, and Bmp7 in mouse embryo forelimbs at different stages of development.
In all panels, anterior is to the top and posterior to the bottom, and all except Bmp4 at 14.5 dpc are dorsal views (figure provided by Glenn Winnier, Vanderbilt

В.Hogan,Genes Dev. 1996 10: 1580-1594

with ectopic lens formation (eLens) and a possibility of lens

transdifferentiation (tdLens) are shown in blue and green, respectively.

The ectopic lens formation can occur as a result of perturbed sonic hedgehog (see anterior pituitary) and Wnt signaling (see ectoderm). Missexpression of Pax6 (see ectoderm) and Six3 (see otic placode) can also produce ectopic lenses. Transdifferentiations of corneal epithelium, iris and RPE into lens illustrate reversibility of cellular memory and of epigenetic regulatory mechanisms.

Prog Retin Eye Res. 2007 November; 26(6): 555–597.

mutants. Different vertebral elements are denoted by unique shapes, shown

in the bottom panel .
Aqua-shaded areas demonstrate the regions of anterior homeotic transformations of the somite-derived primaxial phenotypes. Purple-shaded areas show the lateral plate-derived, abaxial phenotypes for each group. The orange background highlights the regions of phenotypic overlap between adjacent paralogous mutants.

http://scienceblogs.com/pharyngula/2007/09/the_hox_code.php

Philip A. Beachy Nature 411, 349-354(17 May 2001)
The analysis of

developmental pathways in cancer is consistent with the following model of tumorigenesis. Tumour initiation involves acquisition of morphologically silent mutations in a normal stem cell (stage 1, S). Such mutations may not directly confer a growth advantage, as they would affect 'caretaker' genes involved in maintenance of genome integrity47 or single alleles of tumour suppressors such as PTCH or APC whose complete loss would directly contribute to the malignant phenotype. Genes involved in progression may also be mutated at this stage, but without a gross phenotypic alteration. These initial events are followed by a mutation leading to expansion of aberrant stem cells (stage 2), which give rise to transit amplifying cells (TA) that differentiate towards all or a subset of the normal terminally differentiated (TD) cell types (premalignant lesion). An increase in stem-cell number leads to disruption of spatial organization of cell proliferation, and proliferating cells are found in regions where no divisions normally occur. At this stage, the cells remain in the epithelial compartment (E). Subsequent mutations (stage 3) and clonal selection lead to more rapid proliferation, an increase in self-renewing divisions and a consequent decrease in differentiation. Further mutations (stage 3) also allow the cells to invade the mesenchyme (M) and metastasize. (