Development Flashcards
Human Developmental Stages
Zygote-> Morula-> Blastocyst-> Gastrulation-> Embryo-> Fetus-> Adult-> gametes*
Zygote
fertilized egg
1 - 8 cell stage
totipotent; removal of 1 or 2 cells at 8 cell stage still results in an entire organism
Morula
16 – early 32 cells; stage before fluid filled cavity forms, inner 8 cells are pluripotent
Blastocyst
early embryo with fluid filled cavity that forms at the 32-cell stage
Inner cell mass (ICM)
pluripotent; source of embryonic stem cells
Trophoblast
forms the embryonic portion of the placenta
Gastrulation
first massive cell movements
Germ Layers
endoderm, mesoderm and ectoderm
Embryo
week 1-8; cell division, cell migration and organ development
Fetus
9 weeks until birth; size increase & organ refinement
Stages of Commitment to Cell Fate
- Specification – fate is still reversible 2. Determination – fate is no longer reversible 3. Differentiation – overt changes in structure & function – looks like muscle & produces structural proteins necessary for function, e.g. muscle
Specification (vs. Determined)
if development proceeds normally, it will become the fate that tissue of the embryo normally becomes; if the environment changes, the cell fate can still be changed
Determined (vs. Specification)
the cell has activated transcription of the genes necessary for a particular fate; the cell will no longer change its fate regardless of the signals received from the environment
Three levels of transcriptional regulation:
- TFs 2. Histone Modifications 3. DNA methylation
TFs in the ICM vs Trophoblast
• Oct4 and Cdx2 are both on in all cells of the 8-cell stage • At the 16 cell stage, the 8 inner cells express Oct4 and the 8 outer cells express cdx2 • Oct4 and Cdx2 repress each other at the level of transcription • Oct4 maintains proliferation and inhibits differentiation in the inner cell mass (ICM)
Heart Differentiation
General: Totipotent–> Pluripotent-> Germ Layer—-> Field—–> Differentiated
Protein expressed
Example:
Heart: 8cell–>pluri–>Meso–> ♥ Field–>♥ Muscle
- Cdx2 8cell
- Oct4 8cell–>pluri
- Bry Meso
- **Nkx2.5 ** ♥ Field–>♥ Muscle
- **Myosin ** ♥ Muscle
- **CardiacActin ** ♥ Muscle
Master Regulatory Genes (MRGs)–
Transcription factors (TFs) that are master regulators of cell fate, they turn on all the genes necessary to confer a specific cell fate
Histone Modifications:
Phosphorylation
Phosphorylation closes chromatin, decreasing transcription, occurs every mitosis
Histone Modifications :
Acetlyation
Acetlyation opens chromatin, increasing transcription
Histone Modifications :
Methylation
increases or decreases transcription depending on the amino acid methylated
- H3K4 methylation opens the chromatin, increasing transcription
- H3K27 methylation closes the chromatin, decreasing transcription
MRG expression regulated by histone methylation
MRGs are bivalently methylated on H3K4 and H3K27 in embryonic stem cells (ES cells), i.e. gene transcription levels are poised to go either way
ii. Nkx2.5 (MRG for heart) is methylated on H3K4 & H3K27 in ES cells, on H3K4 but not H3K27 in heart cells and on H3K27 but not H3K4 in lens cells
iii. Pax6 (MRG for the lens of the eye) is bivalently methylated in ES cells, methylated on H3K4 but not H3K27 in lens cells and methylated on H3K27 but not H3K4 in heart cells
Natural Sources of Stem Cells
i. Zygote until 8 cell stage – totipotent, small number of cells
ii. Inner Cell mass – pluripotent, when transferred to petri dish = ES cells; source for therapeutics
iii. Primordial Germ Cells – totipotent, not used frequently in research because of limited human supply, occur later in development than inner cell mass
iv. Adult Stem Cells – Multipotent, most common therapeutic use is for bone marrow transplant; includes umbilical cord which can be stored and used as a source of blood and associated tissues
Artificial (manipulated/created) stem cells
i. ES cells – ICM from in vitro fertilization treatments moved to petri dish and cultured with a specific set of growth factors and nutrients
ii. Cloning Dolly – somatic nuclear transfer
4 big decisions during embryonic / fetal development
- Gonad: determined by the sex chromosomes: XX = female and XY = male
- Primordial Germ Cells (PGCs)
- Internal Ducts
- External Genitalia
Hermaphrodite
some of the gonadal tissue forms tissues of the ovary and some of the gonadal tissue forms tissues of the testes.
Pseudohermaphrodite
an individual with some sex organs (gonad, ducts or external genitalia) are male and some sex organs (gonad, ducts or external genitalia) are female
Gonad
- Gonads - somatic tissues that form to support the germ cells
- develops from two bilaterally symmetrical mesodermally derived genital ridges adjacent to the kidneys
- Genital ridge is bipotential
- Testes form sertoli (produce anti-mullerian factor [AMF]) and leydig (testosterone producing) cells
- Ovaries form granulose and thecal cells (both produce estrogen & progesterone)
- Sry, the master regulatory gene for testes,
- Sertoli cells secrete a paracrine factor
Sry
- master regulatory gene for testes, causes the production of the proteins necessary to form the cells of the testes: enhances SF1 expression (already turned on in genital ridge), with SF1 induces Sox9 expression which then turns on all genes necessary to produce sertoli cells, including AMF
- master regulatory gene (TF) for Testes
- Expressed in sertoli cells, On Y chromosome
- Turns on directly or indirectly:
- Sox9 (TF)
- Sf1 (TF)
- AMF – from Sertoli cells, paracrine, degenerates mullarian duct
Sertoli cells
secrete a paracrine factor that activates a signaling cascade in the adjacent Leydig cells that maintains SF1 expression in Leydig cells, resulting in the production of the enzymes necessary to produce testosterone
Primordial Germ Cells (PGCs)
- PGCs are derived from non-gonad tissue
- Derived from bipotential tissue
- Migrate into a testes: become sperm
- Migrate into an ovary: become eggs
(true of all of animal kingdom)
Internal Ducts
- Sertoli cells of testes secretes anti-Mullerian factor (AMF) that destroys Mullerian duct
- Leydig cells of testes secrete testosterone, which is necessary to sustain & pattern the Wolffian duct
- Ducts, unlike the other 3 components of the reproductive tract, are not derived from bipotential tissue
- Wolffian duct = vas deferens, epididymis and glands
- Mullerian duct = oviduct, uterus, cervix and upper portion of vagina
External Genitalia
- Perineum – bipotential
- Male = penis, scrotum and anus
- Female = clitoris, labia major & minor and anus
- Dihydrotestosterone (DHT) in embryo required for perineum to develop male genitalia
Wolffian duct
vas deferens, epididymis and glands
Leydig cells of testes secrete testosterone, which is necessary to sustain & pattern the Wolffian duct
Mullerian duct
oviduct, uterus, cervix and upper portion of vagina
Sertoli cells
- of testes
- secretes anti-Mullerian factor (AMF) that destroys Mullerian duct
Leydig cells
- of testes secrete testosterone,
- which is necessary to sustain & pattern the Wolffian duct
Influence of Sry on gonad development
The germ line cells are shaded in red, and the somatic cells are shaded in green and blue. The change from light to darker color indicates that the cell has matured or differentiated.
- The Sry gene acts in a subpopulation of somatic cells in the developing gonad to direct them to differentiate into Sertoli cells instead of into follicle cells.
- The Sertoli cells then induce primordial germ cells to commit to sperm development. They also secrete anti-Müllerian hormone, which causes the Müllerian duct to regress, and they help to induce other somatic cells to differentiate into Leydig cells, which secrete testosterone
- In the absence of Sry, the primordial germ cells commit to egg development, and the somatic cells develop into either follicle cells, which support egg development, or theca cells, which secrete estrogen. Whereas Leydig cells begin secreting testosterone in the fetus, theca cells do not begin secreting estrogen until puberty.
http://www.ncbi.nlm.nih.gov/books/NBK26940/figure/A3716/?report=objectonly
What is a polarity gene?
Typically, a maternally expressed gene
