Lecture 5 - That One Slide

Homodimers forming between Hippo receptors between cells.

What does the Hippo pathway involve?

Through connections made between cells that activate the pathway.

How do Hippo receptors communicate?

Lats phosphorylates Yap, causing Yap degradation.

What happens when the Hippo pathway is active?

Not much Lats activity, resulting in little Yap degradation.

What happens when the Hippo pathway is not very active?

It activates the cdx2 gene, eventually leading to trophoblast formation.

What role does Yap play when it binds with Tead4 in the nucleus?

Yap within the nucleus.

What does Tead4 need to bind and turn on the cdx2 gene?

Oct4 becomes predominant.

What happens when cdx2 is not expressed?

It actively represses Oct4 to prevent confusion in fate determination.

What is the role of cdx2 when active?

Inner cells have more Hippo activation due to high cell density, with more Hippo receptor connections.

How does the Hippo pathway function in inner cells during the morula stage?

Lower Hippo expression because of fewer surrounding cells, allowing Yap to bind Tead4, producing cdx2 and the trophoblast.

What happens in outer cells regarding Hippo expression?

It affects the amount of Hippo pathway activation.

How does cell body position impact Hippo expression?

More trophoblast cells form due to no Hippo signaling, allowing Yap to bind Tead4.

What happens if blastomere cells are isolated from the zona pellucida on a petri dish?

The morula is filled with ICM since Tead4 cannot activate cdx2.

What happens with a loss of function in the Yap gene?

To predict what would occur if certain components are mutated.

Why should you understand the Hippo pathway?

Temporal changes in cell structure and signaling delay fate decisions until compaction increases cell-cell contacts.

Why doesn’t fate determination occur earlier?

Due to varying levels of Hippo expression, with cross-repression ensuring clear fate determination.

Why is the Hippo decision not an all-or-nothing pathway?

High cell density increases connections between Hippo receptors, leading to pathway activation.

How do cell connections influence Hippo pathway activation?

Compaction brings cells closer together, enhancing Hippo receptor interaction and pathway activation.

What role does compaction play in the Hippo pathway?

Because isolation prevents Hippo signaling, allowing Yap to bind Tead4 and activate cdx2.

Why do isolated blastomere cells form more trophoblasts when cultured on a petri dish?

Temporal changes in cell structure and signaling delay fate decisions until compaction increases cell-cell contacts.

What prevents early cell fate decisions before compaction?

Yap would not be degraded, leading to continuous cdx2 activation and excessive trophoblast formation.

What happens if the Lats gene is mutated and non-functional?

cdx2 cannot be activated, leading to more inner cell mass (ICM) cells instead of trophoblasts.

What happens if Tead4 is mutated and cannot bind Yap?

It ensures clear separation of cell fates, preventing mixed or confused developmental signals.

What is the importance of cross-repression between cdx2 and Oct4?

By adjusting Yap activity based on cell position, density, and timing, ensuring correct lineage decisions.

How does Hippo signaling contribute to developmental robustness?

All cells would likely form trophoblasts due to unchecked Yap-Tead4-driven cdx2 expression.

What would occur if Hippo signaling remained inactive in all morula cells?

Connections made between cells, allowing Hippo receptors to interact.

What triggers the activation of the Hippo pathway?

Lats kinase.

What enzyme is responsible for phosphorylating Yap in the active Hippo pathway?

Yap undergoes degradation, preventing it from entering the nucleus.

What happens to Yap when Lats phosphorylates it?

They tend to form the inner cell mass (ICM).

What is the fate of cells with active Hippo signaling?

Yap is not degraded, allowing it to enter the nucleus and bind to Tead4.

What happens to Yap when the Hippo pathway is inactive?

The cdx2 gene.

What gene does the Yap-Tead4 complex activate?

It promotes the formation of the trophoblast.

What is the role of the cdx2 gene in early embryonic development?

By actively repressing Oct4 expression.

How does cdx2 prevent confusion in cell fate determination?

cdx2 would not be activated, leading to a predominance of ICM formation.

What would happen if Tead4 could not bind Yap?

It increases Hippo pathway activation due to more receptor connections.

How does high cell density affect Hippo pathway activation?

They have fewer neighboring cells, leading to less receptor interaction.

Why do outer cells in the morula stage have lower Hippo expression?

Trophoblast cells.

What type of cells form from outer cells with low Hippo pathway activity?

It brings cells closer together, enhancing Hippo receptor interactions.

How does compaction influence Hippo pathway activation?

Yap would not be phosphorylated or degraded, leading to excessive trophoblast formation.

What would be the effect of mutating Lats kinase in the Hippo pathway?

It may cause confusion in cell fate determination, affecting proper lineage specification.

What happens if Oct4 is not repressed during early development?

To maintain clear boundaries between trophoblast and inner cell mass fate decisions.

Why is cross-repression between cdx2 and Oct4 important?

Yap would enter the nucleus, activate cdx2, and the inner cells might form trophoblasts instead of ICM.

What could occur if Hippo signaling remained inactive in inner cells?

By regulating Yap activity based on cell position and density, ensuring proper fate determination.

How does the Hippo pathway help maintain developmental robustness?

Because it operates with varying levels of activity, influenced by cell context and environmental factors.

Why is the Hippo pathway not considered an all-or-nothing mechanism?