Embryonic Development Quiz

Cell Differentiation Control

• Cellular differentiation is the process by which cells or parts of an organism become different from one another and from their previous state.
• It also describes how cells or tissues acquire the ability to perform specialized functions.
• This process is crucial for embryonic development.
• The progression from zygote to adult results from cell division, cell differentiation, and morphogenesis.
• Cells interact with each other and their environment.
• These interactions trigger specific signaling pathways that are either turned 'on' or 'off'.
• These pathways mediate proliferation, differentiation and apoptosis.
• These processes are vital for development.

Objectives

• Understand the cellular differentiation process.
• Understand the factors determining and controlling differentiation.
• Understand factors determining hematopoiesis and muscle cell differentiation.

Differentiation: Stem Cells

• Fertilization of the egg occurs in the oviduct.
• The zygote travels to the uterus for implantation.
• The zygote divides through mitosis (2-cell, 4-cell, 8-cell embryonic stages, etc.).
• The embryo reaches a morula stage (a ball of small cells)
• by the end of the first week, the embryo develops into a blastocyst.

Differentiation: Embryonic Stem Cells

• The blastocyst is a hollow ball of cells.
• It consists of an outer layer of progenitor cells (trophoblast)
• inner cell mass (ICM) which are differentiated embryonic stem (ES) cells.
• The ICM is the source of embryonic stem cells.
• The morula is a mass of cells.
• The blastocyst is a hollow ball with an inner cell mass.

Cytoplasmic Determinants and Inductive Signals

• An egg's cytoplasm contains RNA, proteins, and other substances unequally distributed.
• Cytoplasmic determinants are maternal substances which influence early development.
• As the zygote divides (mitosis), cells have different cytoplasmic determinants, leading to various gene expressions.

Cellular Interactions in Development: Induction

• Interactions between germ layer cells impact stem cell fate and differentiation pathways.
• Induction allows one cell population to influence neighboring cell development, such as mesoderm inducing overlying ectoderm to form neural tissue.
• This process involves binary choices (one signal leads to one differentiation path, and vice-versa),
• gradient mechanisms that rely on signaling molecule (morphogen) concentration to determine differentiated fates.
• cell signal cascades influence neighboring cells' fate.

Cellular Transduction Pathway

• Signaling molecules bind to specific receptors on target cells.
• This binding initiates a signaling transduction pathway.
• The pathway leads to changes in gene expressions.
• Signal transduction pathways and signal receptors play crucial roles in differentiation.

Cell Type Specificity

• Unique cell characteristics arise from differential gene expressions.

Where Does Differentiation Begin?

• Pluripotent stem cells are crucial in the initiation of differentiation.
• Totipotent cells, 8-cell embryo, and the blastocyst play a role. (these are also pluripotent stem cells)
• Undifferentiated stem cells in vivo or in vitro cultures are involved.

Selective Gene Transcription

• Only the genes necessary for a cell's basic metabolism and specialized functions are active in any given cell.
• For example, muscle cells express actin and myosin genes,
• pancreatic cells express digestive enzyme genes, and
• neurons express tubulin and neurotransmitter genes.

Control of Cell Differentiation

• Genomic level control.
• Transcription and post-transcriptional levels.

Micro-RNAs (miRNA)

• miRNA regulates gene expression by targeting mRNA.
• Dicer cuts dsRNA short segments.
• The single strand (miRNA) associates with protein.
• The bound miRNA pairs with complementary mRNA.
• This binding prevents gene expression, degrades mRNA, or blocks translation.

Differentiation of Blood Cells

• Hematopoiesis is the process of making blood cells from stem cells.
• The hematopoietic stem cells produce billions of blood cells to replace aged ones.
• Hemangioblasts are stem cells that give rise to blood vessels.
• Universal blood stem cells form myeloid and lymphoid precursors.
• Myeloid precursors include red blood cells, platelets, and monocytes/granulocytes.
• Lymphoid precursors create lymphocytes for immunity. (B and T cells).

Hematopoiesis Regulation

• Cytokines and growth factors regulate hematopoiesis, orchestrating diverse progenitor and pluripotent stem cell differentiations.
• Key growth factors like FGF, Activin, and BMP-4 regulate pluripotent differentiation.
• The cytokine CSF-1 directs GATA-1+ committed progenitors.

Genetic Control of Muscle Cell Differentiation

• Myoblasts have master regulatory genes that produce proteins, committing cells to become skeletal muscle (e.g. myoD)
• MyoD is a transcription factor binding to enhancers.
• MyoD (along with related myogenic factors) initiates muscle-specific protein expression.
• These factors are basic helix-loop-helix transcription factors that regulate muscle cell differentiation.

Terminal Differentiation

• Cells reach a stage where they cannot progress down any particular lineage.
• Examples include neurons, skeletal muscle cells, and keratinocytes.
• Fibroblasts are excluded as they can migrate to wounds and express different markers depending on the environment.

Cell Properties

• Irreversible differentiation (e.g. mature keratinocytes): DNA synthesis stops.
• Reversible differentiation (e.g. hepatocytes): Re-induction of functions like albumin synthesis.

Markers of Differentiation

• Markers indicate the mature phenotype of terminally differentiated cells. - Examples include cytokeratins for epithelium, hemoglobin for erythrocytes, albumin for hepatocytes, and so on.

Regulation of Differentiation

• Cell-cell interactions (homotypic and heterotypic) influence differentiation through contact, diffusible paracrine factors.
• Extracellular matrix and systemic factors (hormones and growth factors).
• Oxygen tension affects cells' shape and polarity, differentiation in vitro.

Induction of Differentiation: Cell Interaction

• Heterotypic cell interactions and reciprocal paracrine interactions guide differentiation.
• Mutual interaction between diverse germ-layer cells promotes differentiation (differentiation).
• Paracrine interactions in epidermal maturation.

Diseases Associated with Differentiation

• Pulmonary fibrosis results from uncontrolled myofibroblast and fibroblastic activity, leading to excessive collagen deposition.

Differentiation & Diseases

• Cancer is a failure of cells differentiating normally.
• Poorer differentiation in cancer histology correlates with poorer patient survival.
• Tumor cells can be induced to differentiate in tissue culture.

Differentiation & Malignancy

• Cancer involves a loss of normal cell differentiation.
• Patients with poorly differentiated tumours have a lower survival rate.
• Tumour cells can be induced to differentiate in vitro.

Table 17.2. Soluble Inducers of Differentiation

• This table lists chemical inducers (e.g. DMSO, sodium butyrate, N-methyl formamide) and their impacts on various cell types during differentiation.

The Clinical Use of Retinoids

• Retinoids are used in cancer therapies and prevention.
• They impact various aspects of cell behavior including (differentiation), mediated by the nuclear receptor superfamily.

Test your knowledge on key concepts in embryonic development, including the roles of cytoplasmic determinants, the blastocyst structure, and inductive signaling processes. This quiz covers essential stages from the morula to the specification of cell types.