Gene regulatory networks and Cell Types

What are the three types of regulation?

1) Positive regulation - gene 1 upregulated expression of genes 2 and 3

2) Negative regulation - gene 1 downregulates expression of downstream genes

3) Combinatorial regulation - both genes 1 and 2 regulate gene 3 (most common as target gene only expressed with right combo of activating and repressing signals)

Are GRN’s hierarchical?

Yes they are as genes at top of the pathway are expressed earlier in development and regulate genes below.

What are levels of GRN hierarchy in relation to evo changes?

Changes high up = changes in phylum characteristics

Changes in signalling pathways = changes in class, order or family

Changes in differentiation genes = species level differences

What are the three key components in network?

Transcription factors, signalling molecules and differentiation genes

Describe transcription factors

Transcription factors are proteins that bind directly to specific DNA sequences near a gene. By binding they determine when, where and how strong target gene is transcribed. They are categorised based on DNA binding domain.

Why are cis-regulatory elements most targeted for evo-changes?

Cis regulatory elements are areas that do not code for amino acids but control where and when gene is expressed. They allow for regulatory changes without changing functional protein and limits impact to single target gene.

Describe the pathway

1) Ligands are signalling molecules that travel through space and create a concentration gradient, they then bind to receptors on surface of target gene.

2) This binding to receptor causes conformational change and this sends signal across cell membrane which triggers cascade of

3) Intermediates relay and amplify this signal inside the cell and the final cytoplasmic protein activates and modifies

4) Transcription factors which bind to specific CRE and regulate expression by either activating or repressing target gene.

What do differentiation genes do?

Differentiation genes are workers that actually build the final product, resulting in phenotype.

Explain sea urchin and sea star example (Hinman et al. 2003)

Both sea urchins and sea stars use same kernel in development of endomesoderm specification. The TF and regulatory connections used are very similar. The networks however differ in output where sea urchins have co-opted TF like Tbrain to activate genes for skeletal development while starfish use it to form different structures.

What is a kernel?

An ancient, highly conserved, inflexible core gene network

What are cell types?

Cell types are the basic functional units of an organism, every species has multiple types. They are distinct groups of cells governed by a specific gene regulatory network known as a Core Regulatory Complex. Complexity increases as clades age because multifunctional cells undergo Functional Segregation, Divergence, and Recruitment.

How does Pax6 act as example of functional segregation of cell types?

While the morphology of eyes across the Bilateria is very different, the underlying photoreceptor cell type exhibits deep homology. This is shown through conservation of Pax6, which functions as a Terminal Selector within the cell's Core Regulatory Complex. This suggests that complex eyes evolved via Functional Segregation of an ancestral, Pax6-regulated multifunctional cell into the specialised sister cell types we see today

How does Cambrian explosion show evidence of function segregation and divergence?

The Cambrian Explosion acts as an example period of rapid cellular innovation. The sharp increase in organismal complexity during this era is directly proportional to the rise in the Number of Cell Types within evolving clades. This expansion was largely driven by Functional Segregation, where multifunctional ancestral cells specialized into discrete 'sister' types, such as the divergence of general ectoderm into specialized sensory and neural cells. This increased 'cellular inventory' provided the modular building blocks necessary for the evolution of complex organs.

How do cnidocytes act as evidence of evolution via recruitment of cell types?

The cnidocyte represents a classic example of evolution via recruitment (co-option), where a novel cell type is formed by repurposing an ancestral genetic toolkit. Research indicates that cnidocytes are essentially specialised sister cells to neurons, sharing a homologous Core Regulatory Complex (CoRC). By co-opting the pre-existing network for sensing and secretion, and integrating it with new structural proteins (apomeres), the cnidocyte emerged as a unique evolutionary unit.

What is Transcriptome Age Index?

Transcriptome Age Index is a measurement tool used in evo-devo which integrates the average age of all protein coding genes expressed in a cell, weighted by their expression levels. Low TAI identifies ancestral "founder" cells, while High TAI identifies "innovator" cells (like cnidocytes) that use ancient network (neurons) but recruited younger genes to gain new function (stinging).