Download Axis formation in Vertebrates I. D

1869-1941
Nobel Prize 1935
Otto Mangold
1891-1962
Hilde Mangold
1898-1924
Pieter Nieuwkoop
1917-1996
AXIS FORMATION II.
Vertebrates
„Theories come and theories go. The frog remains.”
Jean Rostand (1960)
XENOPUS: D-V
THE THREE SIGNAL MODEL (3SM)
2
before
gastrulation
during
gastrulation
1)
vegetal cells secrete a mesendoderm-inducing factor
that converts the marginal zone (MZ) into a ring of
mesoderm
2)
The vegetal cell mass is subdivided into dorsal (=
Nieuwkoop Centre) and ventral parts that induce
dorsal and ventral mesoderm, respectively;
3)
the most dorsal mesoderm (Spemann’s / SpemannMangold organiser /SMO/) secretes signals that
establish DV polarity by promoting dorsal identity

Spemann-organizer induces
patterning of the germ layers
the
secondary
Experiments leading up to the three-signal model (3SM). a Schematic of an amphibian late blastula
stage embryo after germ layer induction; animal points up, vegetal points down, ectoderm is shown in
blue, mesoderm in red, endoderm in yellow. b When cultured in isolation, animal and vegetal explants
differentiate into ectoderm and endoderm, respectively; in animal–vegetal co-cultures, mesoderm (and
some endoderm) is induced in the animally derived tissue suggesting an inducing signal emanating from
the vegetal tissue (red arrows). c Dorsovegetal cells induce dorsal mesoderm (purple) whereas
ventrovegetal cells induce ventral mesoderm, even if the animal tissue is rotated by 180. d The 3SM for
germ layer formation: (1) a signal emanating from vegetal cells of the embryo induces the mesoderm in
an equatorial ring (red arrows), (2) a signal from dorsovegetal cells dorsalises the mesoderm on the
dorsal side (purple arrow) and (3) signals from the dorsal mesoderm (Spemann’s organiser) pattern the
embryo along its DV axis (black arrow). D, dorsal; V, ventral
Maternal heritage → 3SM: STEP 1
secreted TGF-b proteins:
 Activin
 Xnrs (Xenopus Nodalrelated factors)
 activation of the
Smad2/4 pathway
in the MZ
Buc: Bucky ball
Macf1: Microtubule-actin cross-linking factor 1
 MZ → mesoderm
MZ→MES
Vg1, VegT
activin, Xnr
↑
Vg1, VegT
4
Xenopusban a MZ több rétegű
• a felszíni réteg entoderma precursorokat ad,
• a mélyebb rétegek mesodermalis precursorokat adnak
Rana:
• az MZ felszíni rétege is ad mesodermalis sejtvonalakat
Kofron et al.,
Dev 2007
3SM STEP 2:
The polarizing factor b-catenin
and the „paternal heritage”
 localization of β-catenin accumulation
Dobrowolski and De Robertis, Nat. Rev. 2012

Wnt11 mRNA and protein  signaling ventrally → balancing of Axin level ventrally
by sequestration of the axin containing „destruction complex” into MVB → newly
synthesized β-catenin accumulation
b-catenin accumulation → Nieuwkoop centre
Eomes: Eomesodermin
• direct result of TGFbBMP
mediated mesoderm
induction
• T-box transcription factor
Eomes→Xbra
SMO
MZ
Nieuwkoop centre
Goosecoid, etc.
Nieuwkoop Centre
↓
Spemann-Mangold Organizer (SMO)
7
MZ
Vg1, VegT
Activin, Xnr →
ADMP (anti-dorsalizing morphogenetic protein,
a BMP-like paracrine factor)
Functions of the SMO
 The ability to self-differentiate dorsal (axial) mesoderm (prechordal plate: pharyngeal entoderm,
axial head mesoderm, chordamesoderm) ((= roof of the archenteron in Rana and
Hemichordata! (see the neural induction))
 Initiate the gastrulation – remember bottle cells and the mechanoeffector b-catenin
 The ability to dorsalize
3SM STEP 3
 the surrounding mesoderm into paraxial
(somite-forming) mesoderm when it would
otherwise form ventral mesoderm
 by Smad2/4, Twin/ Siamois → chordin, noggin,
follistatin secretion by axial mesoderm : Bmp
inhibitors
SMO
chorda
10
•
 Dorsalizing the ectoderm =
induce formation of the neural
tube
 nervous system forms from
that region of the ectoderm
that is protected from
epidermal induction by
BMP-inhibiting molecules
A Hemichordata ősbéltető
homológ a Chordata gerinchúrral,
De
•
Rana ősbéltető
Nem zajlik le az enterocoelia
folyamata, így nem alakul ki
lateralis mezoderma (hiányzik pl. a
somitomeria)
Hemichordata neuruláció, Balanoglossus simodensis
Ketzer András BSc szakdolgozata, 12. ábra
(Miyamoto és Wada, 2013)
Larsen’s Human embriology
 Fate of the ectoderm / NEURULATION
 (1) "default fate„ is to become neural tissue (this feature originates from the nuclear b-catenin);
11
 (2) certain parts of the embryo induce the ectoderm to become epidermal tissue by secreting
BMPs (Bmp4/2/7);
 (3) the organizer tissue acts by secreting molecules that block BMPs, thereby allowing the
ectoderm "protected" by these BMP inhibitors to become neural tissue.
Deuterostomia – Prostomia
D-V axis inversio
12
CNS
CNS
Deuterostome
anchestor,
living
Hemichordata
INVERTER: SMO = „Vertebrate innovation”
References
13

Gilbert, S.F. Developmental Biology, 9th ed. 2010

Kiecker, C., Bates, T. Bell, E. Molecular specification of germ layers in vertebrate embryos Cell. 2016 Mol. Life Sci. 73:923–947 DOI
10.1007/s00018-015-2092-y

Kofron, M. at al. 2007 Wnt11/β-catenin signaling in both oocytes and early embryos acts through LRP6-mediated regulation of
axin. Development 134: 503-513; doi: 10.1242/dev.02739

Levin, AJ., Brivanlou, AH. Proposal of a model of mammalian neural induction. 2007 Developmental Biology 308: 247–256
doi:10.1016/j.ydbio.2007.05.036

Rossant, J. Tam, PPL. Blastocyst lineage formation, early embryonic asymmetries and axis patterning in the mouse. 2009
Development 136: 701-713; doi: 10.1242/dev.017178

Saitou, M., Yamaji, M. Germ cell specification in mice: signaling, transcription regulation, and epigenetic consequences. 2010
Reproduction 139: 931-942 2010, doi: 10.1530/REP-10-0043