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The fate of neural crest cells
The mesoderm
Sex determination
Medical implications of
developmental biology
세포생물학 3 (임현정)
June 12, 2009
Specification of the NC cells
“중간” 정도의 농도로 BMP, Wnt, FGF 류의 paracrine
factor들이 존재할 때 neural plate border specifiers라
불리우는 전사요소들이 유도된다. 이들은 neural crest
specifiers라 불리우는 전사요소인 Slug와 FoxD3를 유도한다.
Slug는 neural crest cell들이 epithelium을 떠나 이동해 가는데
필요한 것으로 보임.
NC is a transient structure.
1.Cranial NC
2.Trunk NC
3.Vagal and sacral NC
4.Cardiac NC
Regions of the chick neural crest. The cranial neural crest migrates into the pharyngeal arches and the face to form
the bones and cartilage of the face and neck. It also produces cranial nerves. The vagal neural crest (near somites 1-7)
and the sacral neural crest (posterior to somite 28) form the parasympathetic nerves of the gut. The cardiac neural
crest cells arise near somites 1-3; they are critical in making the division between the aorta and the pulmonary artery.
Neural crest cells of the trunk (about somite 6 through the tail) make sympathetic neurons and pigment cells
(melanocytes), and a subset of these (at the level of somites 18-24) form the medulla portion of the adrenal gland.
Neural crest cell migration in the trunk of the chick embryo (Part 1)
Path 1 (Ventral pathway): ventrally 이동해 sclerotome의 anterior half 부분 통과
(ganglia, adrenomedullary cells, etc)
Path 2 (Dorsolateral pathway): epidermis와 dermis 사이 통과
(pigment-producing melanocytes)
* Sclerotome: somite의 일부로 vertebral cartilage를 만듬
13.3 Neural crest cell migration in the trunk of the chick embryo (Part 2)
Anti-HNK1으로 염색 (NC marker)
Segmental restriction of neural crest cells and motor neurons by the ephrin proteins of the sclerotome (Part 1)
(HNK1 staining)
Segmental restriction of neural crest cells and motor neurons by the ephrin proteins of the sclerotome (Part 2)
The mesoderm
The major lineages of the amniote mesoderm (Part 1)
The major lineages of the amniote mesoderm (Part 2)
* Trunk mesoderm
1. Chordamesoderm: notochord 형성
일시적 구조로 neural tube 유도
2. Paraxial mesoderm: somite 형성
등쪽의 connective tissue 형성
(bone, muscle, cartilage, dermis)
3. Intermediate mesoderm: urogenital system
(kidney, gonads)
4. Lateral plate mesoderm: notochord에서 가장 멀다
Heart, blood vessels, blood cells
Limb(사지)의 중배엽성 구조 형성
Gastrulation and neurulation in the chick embryo, focusing on the mesodermal component
Paraxial mesoderm
* Paraxial mesoderm은 neural fold 시기에 somite 형성 (block of cells)
Mature somite:
a. Sclerotome – vertebrae와 rib cartilage 형성
b. Myotome – 등쪽의 musculature, ribs, limbs
c. Dermatome – 등쪽의 dermis (진피)
(Surface ectoderm 을 벗긴 상태)
14.3 Specification of somites
Pax3 staining (somite의 marker)
Noggin: BMP antagonist
Specification of somites: chick의 lateral plate
mesoderm이 형성될 곳에 Noggin-secreting cell들을
넣어 주니 paraxial mesoderm (somite-like)이
유도되는 것을 보여줌 (bracket 친 곳 )
Notch signaling and somite formation (Part 1)
Notch signaling and somite formation (Part 2)
Somitogenesis
1.Periodicity
2.Fissure formation
3.Epithelialization
4.Specification
5.Differentiation
Somite의 A/P axis에는 Hox gene들이 관여
Somite formation correlates with the wavelike expression of the hairy1 gene in the chick
Somite 수: chick은 50개, mouse는 65개
(Embryonic development 과정 중 현재 몇 개의 somite가 형성이 되어 있는지 보는 것은 발달단계의
좋은 indicator)
Epithelialization and de-epithelialization in somites of a chick embryo
Segmental plate mesoderm transplanted into a different region in a younger embryo differentiates
according to its original position
Thoracic somite로 분화했을 segmental plate mesoderm부분을 younger embryo의
cervical somite가 될 부분으로 transplant하면 grafted mesoderm이 원래의 성격을 따라
rib을 만든다.
Intermediate mesoderm
Signals from the paraxial mesoderm induce pronephros formation in the intermediate
mesoderm of the chick embryo
(A) The paraxial mesoderm was surgically separated from the intermediate mesoderm on
the right side of the body. (B) As a result, a pronephric kidney (Pax-2-stained duct)
developed only on the left side. (C) Lim1 expression in an 8-day mouse embryo, showing
the prospective intermediate mesoderm.
General scheme of development in the vertebrate kidney
(A) The original tubules, constituting the pronephros, are induced from the nephrogenic
mesenchyme by the pronephros by the pronephric duct as it migrates caudally. (B) As the
pronephros degenerates, the mesonephric tubules form. (C) The final mammalian kidney,
the metanephros, is induced by the ureteric bud, which branches from the nephric duct.
(D) The intermediate mesoderm of a 13-day mouse embryo showing the initiation of the
metanephric kidney while the mesonephros is still apparent. The duct tissue is stained
with a cytokeratin antibody.
Sex determination
Chromosomal sex determination in mammals
1. Primary sex determination: chromosomes, gonads
Y chromosome: testis-determining factor
2. Secondary sex determination: gonad 이외의 phenotype 결정
대부분 gonad에서 나오는 hormone들에 의해 결정
Y chromosome
X chromosome
Sex determination in mammals
Differentiation of human gonads shown in transverse section (Part 1)
Differentiation of human gonads shown in transverse section (Part 2)
Differentiation of human gonads shown in transverse section (Part 3)
The development of the gonads and their ducts in mammals (Part 1)
The development of the gonads and their ducts in mammals (Part 2)
The development of the gonads and their ducts in mammals (Part 3)
An XX mouse transgenic for Sry is male
Ability of Sox9 to generate testes
Migration of the mesonephric cells into Sry+ gonadal rudiments (Part 1)
Migration of the mesonephric cells into Sry+ gonadal rudiments (Part 2)
Phenotypic sex reversal in humans having two copies of the DAX1 locus
Dax1 expression in the mouse genital ridge
Possible mechanism for primary sex determination in mammals
Primordial Germ Cells
1. All gametes arise from PGCs.
2. Frogs, nematodes, flies, etc.: PGCs are autonomously specified by cytoplasmic determinants
(Germ Plasm) during cleavage.
3. Mammals, etc.: PGCs are specified by interactions among neighboring cells.
Chromosome diminution (roundworm Parascaris)
이로 인해 많은 유전자가 사라지나 germ cell이
될 세포에서는 모든 유전정보가 유지된다
원심분리로 인해 germ plasm이
두 개의 세포에 나뉘게 되어 두
개의 stem cell이 생긴다
“Germ plasm”: 특정 RNA나 protein이 이를 specify 한다
19.3 The pole plasm of Drosophila
The pole plasm of Drosophila
19.6 Germ plasm at the vegetal pole of frog embryos
Germ plasm at the vegetal pole of frog embryos
Xcat2 mRNA의 localization
Day 7 mouse embryo
포유류에서는 germ
plasm이 없다. 그대신
embryo에서 유도되어
만들어진다.
(요막)
(Epiblast)
19.7 Specification and migration of mammalian primordial germ cells
Day 7 mouse embryo
Morphogens
Extraembryonic ectoderm과 epiblast junction에서
germ cell들이 유도되어 나온다.
Posterior epiblast 부분으로 PGC가 들어온다.
fragilis (+)
stella (+)
blimp1 (+)
Expression of Oct4 mRNA correlates with totipotency and ability to form germ cells
Inner cell mass
Spermatogonia
Posterior
Epiblast (8.5)
Migrating
PGCs (10.5)
Oogonia
19.14 Primoridal germ cell migration in the mouse (Part 1)
Hindgut
19.14 Primoridal germ cell migration in the mouse (Part 2)
Medical Implications of Developmental Biology
Down syndrome
Positional cloning of the human PAX6 gene (Part 1)
Positional cloning of the human PAX6 gene (Part 2)
Microphthalmia syndrome in humans and mice (Part 1)
Microphthalmia syndrome in humans and mice (Part 2)
Mosaic and relational pleiotropy
In vitro fertilization
Preimplantation genetics is performed on one or two blastomeres taken from an early blastocyst
Periods and degrees of sensitivity of embryonic organs to teratogens
Comparison of a brain from an infant with fetal alcohol syndrome with a brain from a normal infant
of the same age
Possible mechanisms producing fetal alcohol syndrome (Part 1)
Possible mechanisms producing fetal alcohol syndrome (Part 2)
Effects of exposure to diethylstilbestrol on the female reproductive system (Part 1)
Effects of exposure to diethylstilbestrol on the female reproductive system (Part 2)
In situ hybridization of a Hoxa10 probe shows that DES exposure represses Hoxa10
Vectors used in gene therapy (Part 1)
Vectors used in gene therapy (Part 2)
Germline gene transmission
Five ways of obtaining human pluripotent stem cells (Part 1)
Five ways of obtaining human pluripotent stem cells (Part 2)
Embryonic stem cell therapeutics (Part 1)
Embryonic stem cell therapeutics (Part 2)
Embryonic stem cell therapeutics (Part 3)
Repair of Rag2 deficiency by therapeutic cloning