Mechanisms in Embryo development

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General Development:

2 phases:

Prenatal (before birth) and postnatal (after birth)

Embryology is the study of fertilisation to birth (prenatal):

Embryonic period: all major organ systems established

Foetal period: Growth and organ refinement

Clinical significance:

Pre-implantation developmental abnormalities: failure to implant within uterus - failed or ectopic pregnancies

Severe embryonic period development abnormalities: teratogen exposure and infection during weeks 3-8 can cause neural tube defects and other defects

Foetal period abnormalities: Malformation or mechanical abnormalities

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Initial Embryo Development:

Zygote:

One cell embryo in which maternal and paternal fuse, process called syngamy

Cleavage stage development:

Zygote divides into 2 cell embryo by day 2

Cleavage: mitotic division which increases cell number but not volume

Process through 2-cell, 4-cell, 8-cell

early embryonic cells known as blastomeres

Morula:

Cluster of cells form morula

Compaction: Outer cells interconnect and flatten

Blastulation:

First differentiation event: Outer cells develop into trophectoderm (foetal placenta), inner cells develop into inner cell mass (ICM, embryo proper)

Fluid-filled cavity develops inside trophectoderm and blastocyst formed, which expands

Bilaminar embryonic disc formation:

Expanded blastocyst hatches from zona pellucida (prevents extra sperm from getting through)

ICM further differentiates into epiblast and hypoblast

Erosion of overlying trophectoderm (only in domestic species) forms bilaminar embryonic disc

Elongation and gastrulation:

Embryo becomes ovoid and then tubular/filamentouse

Trophectoderm folds over embryonic disc and fuses to form embryonic cavity (only in domestic species)

Trilaminar embryinic disc forms by gastrulation: Somatic germ layers - ectoderm, mesoderm & endoderm. Sex cell progenitors: primordial germ cells

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Differentiation:

Over 230 different cell types in mammalian adult

Differentiates from a less to more specialised cell type regulated by differential gene expression

Initially reversible (cell specification) then irreversible (cell determination)

Induction:

Interaction between 2 or more cells that cause differentiation

Target cells need to be competent during critical period. Differentiation or cell death.

Signalling molecules act as paracrine factors between adjacent cells. 4 major families: Fibroblast Growth Factor (FGF) Hedgehog Wingless (Wnt) and Transformation Growth Factor-β (TGF-β) super family

Cells lose their ability to form multiple lineages as they differentiate

Cellular Potency:

Zygote and blastomeres up to morula stage are totipotent (form all cells of the embryo, placenta & extraembryonic membranes)

ICM & epiblast (1st & 2nd differentiation event) are pluripotent (form all cells of the embryo only)

ectoderm, mesoderm & endoderm are multipotent (form all cells within each specific somatic germ cell lineage)

tissue-specific progenitor or precursor cells are unipotent (form single types of differentiated cells only)

fully mature specialized cells are terminally differentiated (can no longer divide/differentiate)

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Molecular controls:

Transcription factors activate expression of developmentally important genes

Epigenetic changes stably activate or repress gene transcription via:

DNA methylation: insertion of methyl groups into promoter = gene silencing

Acetylation of histones: induces open chromatin = gene transcription

Polycomb-trithorax gene regulation: change in chromatin structure to repress (Polycomb) or activate (trithorax) gene transcription

Epigenetic Modification and Imprinting:

DNA methylation silences and demethylation allows transcriptions

2 rounds of epigenetic reprogramming occur during development:

demethylation of primordial germ cells entering primitive gonad → erase then reset imprinted genes → sex-specific monoallelic gene expression

after fertilization, demethylation of paternal (zygote) then maternal (cleavage - morula) genome → erase then reset embryo development genes → imprinted genes remain methylated

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Patterning and Morphogenisis

The organization of cells into tissues (patterning) & internal/overall shaping of organs (morphogenesis)

Body axis formation:

differentiated cells spatially organize in 3 dimensions: dorso-ventral – formed at blastocyst stage, cranio-caudal – formed during gastrulation, proximo-distal – formed during limb formation

mediated by concentration gradients of signaling molecules

Homeobox (Hox) genes:

provide cells with positional identity along cranio-caudal axis

grouped in 4 clusters: Hox-A, Hox-B, Hox-C & Hox-D

a gradient of retinoic acid induces expression of Hox genes in 3’ (early anterior patterning) to 5’ (late posterior patterning) order