2-26 Mechanisms of Development

Question 1

What is a homologous gene?

Answer 1

A homologous gene (homolog) is a gene similar in structure, evolutionary origin, and likely function to a gene in another species.

ex) A fruit fly gene that encodes a protein that performs the same function as the mouse version of that gene and protein.

Question 2

What is genome equivalence?

Answer 2

Each somatic cell has the same chromosomes as all other somatic cells (the chromosomes in each cell of an organism are mitotic descendants of the chromosomes present at fertilization).

Somatic nuclear transfer (cloning) provides evidence that all cells contain the same genes.

Question 3

What is differential gene expression?

Answer 3

Though genetic material is identical in every cell, gene expression can be regulated at multiple levels such that different cell types can produce different sets of proteins. The expression of different sets of genes in different cells coordinates development by controlling four essential cellular processes by which the embryo is constructed:

1. Cell proliferation: producing many cells from one.
2. Cell specialization: creating cells with different characteristics at different positions.
3. Cell interactions: coordinating the behavior of one cell with that of its neighbors.
4. Cell movement: rearranging the cells to form structured tissues and organs.

Question 4

What are the 3 major cell-cell interactions during embryological development?

Answer 4

1. Induction
2. Cell-cell signaling (morphogens)
3. Signaling cascades

Question 5

What is induction?

Answer 5

An interaction between different groups of cells. One group (inducer) changes the behavior of the other group (responder; responder must be competent, or able to respond).

Inductive signals can be short range (e.g., those transmitted via cell-cell contacts) or long range (mediated by molecules that can diffuse through the extracellular medium).

ex) The optic vesicle is able to induce lens formation in the anterior portion of the ectoderm but not in the trunk or abdomen. If the optic vesicle is removed, the surface ectoderm forms either an abnormal lens or no lens. Most other tissues are not able to substitute for the optic vesicle as an inducer.

Question 6

What is a morphogen?

Answer 6

A paracrine signaling molecule secreted to act directly on neighboring cells to produce specific responses that depend on concentration of the morphogen.

A morphogen can specify more than one cell type by forming a concentration gradient; e.g., a high concentration may direct target cells into one developmental pathway, an intermediate concentration into another, and a low concentration into yet another. Morphogen gradients provide spatial information that subdivides a field of cells by inducing or maintaining the expression of different target genes at distinct concentration thresholds.

ex) Nodal experiments in zebrafish, which imply that Nodal created a gradient; the types of genes turned on depended on the distance from the source cell

Question 7

How are signaling cascades involved in embryological development?

Answer 7

Many inductive molecules and morphogens transmit their signals through the cell membrane and to the cell nucleus via signal transduction pathways.

Common theme: Extracellular ligand binds to cell membrane receptor → Δ rcptr. conformation → Δ rcptr. enzymatic activity in cytoplasm → activation of cascade of enzymatic (phosphorylation) processing of several intracellular proteins → activation of TF that binds DNA and alters gene expression in the cell

ex1) Transforming growth factor-β (TGFβ). The TGFβ family of secreted molecules binds receptors at the cell surface of responding cells. Smad proteins are then phosphorylated and enter the nucleus to modulate gene transcription.
ex2) Hedgehog signaling

Question 8

What is heterotaxy syndrome?

Answer 8

Situs ambiguus, or defects during embryogenesis that perturb left-right asymmetry of only SOME organs, causing a broad spectrum of congenital malformations that compromise organ function.

As opposed to situs solitus (normal orientation of internal organs) or situs inversus totalis (mirror-reversal of normal left-right organ asymmetry).

Question 9

What is a key cause of left-right body axis formation?

Answer 9

Asymmetric gene expression.

• Nodal gene, coding for a member of the TGFβ superfamily, is expressed asymmetrically in the organizer/node region (in the mouse, chick, frog and zebrafish) →
• Signal relayed to create a broad stripe of Nodal expression in the lateral plate mesoderm along the left side ONLY

This tightly regulated pattern is a good example of differential gene expression.

Question 10

What is Kartagener’s syndrome?

Answer 10

A syndrome that results from defects in molecules needed for the beating of cilia and flagella.

1. Infertility (immotile sperm)
2. Chronic bronchitis and sinusitis (defective resp. tract cilia)
3. 50% of individuals have left-right internal organ inversion

This syndrome was the first suggestion that ciliary beating somehow controls which way the left-right body axis is oriented.

Question 11

What are thought to be some of the molecular controls for formation of the left-right body axis?

Answer 11

Cilia in the gastrulatory node that drive fluid to the left side → fluid flow ?→? asymmetric gene expression (Nodal in the l. lateral mesoderm plate)

• One hypothesis for asymmetric fluid flow → orientation of LR axis: morphogen gradient
• Nodal activates downstream target genes, incl. Pitx2 and Lefty
• Lefty: restricts the asymmetric domain of Nodal signaling
• Pitx2: TF expressed on the l. side of the developing heart and gut; thought to regulate expression of genes that mediate asymmetric morphogenesis of these organs