Lecture 16 - W25 Recording

Introduction

• Appreciation for class attendance and engagement.

• Focus on the timing of soul mate development as a key concept in developmental biology.

• Importance of understanding the timing for the upcoming exam.

Concept of Development Timing

• Development likened to a domino effect; each event triggers the next in a precise order.

• Example given of fertilization initiating molecular events (e.g., calcium release).

• Developmental sequences must occur in a specific order for viability.

Somite Formation as a Case Study

• Somites serve as a primary example of developmental timing.

• Development is intricate and interconnected; somite formation illustrates these complexities.

• A review of somites: structures that arise post-gastrulation, regulate segmental organization in the embryo.

Speed of Developmental Signals

• Fast signaling: changes in the function of pre-existing proteins; occurs quickly (e.g., PDGF pathway activated in seconds).

• Slow signaling: involves transcription, translation, and requires more molecular machinery; takes minutes to hours.

• Other factors influence developmental timing beyond just signaling speed.

Understanding Somites

• Somites form immediately after differentiation of embryonic layers: ectoderm, mesoderm, and endoderm.

• Mesoderm eventually transforms into somites, essential for forming various structures (bones, muscles).

• Experimental work with chicken embryos providing insights into somite formation patterns.

Observation of Somite Development in Chickens

• Visual observation of somite formation direction: from head ( anterior) to tail ( posterior).

• Understanding cellular proliferation rates as a mechanism influencing somite spacing and formation.

Notch Signaling and Somite Timing

• Deletion of the Notch receptor disrupts somite formation timing without completely inhibiting it.

• Notch activation is essential for the correct timing of somite formation.

Lateral Inhibition

• Defined as a mechanism for neighboring cells to inhibit each other's differentiation.

• Notch is involved in lateral inhibition but is distinct from the timing mechanism for somite formation.

Mechanism of Somite Formation Timing

• Notch signaling, upon activation by Wnt and FGF proteins, leads to expression of HES genes in the presomatic mesoderm.

• HES gene expression oscillates; delays in feedback mechanisms impact timing of somite differentiation.

• Gradient of Wnt and FGF at the tail region influences cell signaling and oscillation cessation.

Genetic and Molecular Relationships in Somite Timing

• The oscillation of HES genes in the presence of Notch signaling prevents premature differentiation.

• Once Wnt and FGF levels drop, oscillations cease triggering somite formation; peak and trough levels define somite boundaries.

Understanding Oscillation Frequency

• The speed of oscillation is dependent on the feedback delay in gene expression.

• Future alterations in timing (longer somites) can occur by tweaking these molecular feedback cycles.

Connection to Nervous System Development

• Overview of growth cone mechanisms in neuronal development, timing implications for axon guidance.

• Neurons' complexity requires precise timing in both growth and differentiation.

Growth Cone Guidance in the Spinal Cord

• Commissural neurons must navigate toward the midline (floor plate) using netrin and slit signaling pathways.

• Netrin guides growth cones towards the floor plate, while slit signaling causes repulsion after reaching the peak of netrin.

Summary and Exam Preparation

• Understanding timing and mechanisms for somite differentiation, growth cone guidance is critical for the final exam.

• Insights into the roles of key proteins (Notch, Wnt, FGF) and feedback systems in developmental timing.

• Students encouraged to seek additional help if needed.