Investigating the role of transcription factor Sox17 in formation of the zebrafish left/right organiser.

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The placement of internal organs during vertebrate development, such as liver on the right, and heart and pancreas on the left is governed by a transient embryonic structure generically referred to as the left/right organiser, which in zebrafish is named Kupffer's vesicle (KV). Formation of the progenitor cells that give rise to the KV is dependent on the transcription factor sox32, which also controls the formation of endoderm. Endoderm is one of three primary germ layers formed within the vertebrate embryo, and makes major contributions to the respiratory and gastrointestinal tracts and associated organs such as the liver and pancreas. Zebrafish sox32 and sox17 arose from duplication of ancestral Sox17, hence mammalian Sox17 is the closest homologue to both. However, how the function of these two zebrafish genes reflect each other and mammalian Sox17 requires further investigation. While sox32 is required for both endoderm and DFC fates, sox17 expression is dependent of Sox32 function, therefore whether both cell identities are directly dependent on Sox32 rather than downstream target Sox17 is unclear. My previous research has suggested that Sox17 is able to rescue the loss of KV progenitors but not endoderm in sox32-deficient embryos. This suggests that Sox32 and Sox17 may act independently to specify these two distinct cell types. We will explore if and how Sox32 and Sox17 act independently or redundantly to specify endoderm and KV progenitors, and how this reflects ancestral Sox17 function.This project will uncover key molecular details of how the KV forms, and thus how vertebrate left/right patterning is achieved. It will have major implications in understanding the function of Sox proteins that are implicated in a range of biological processes and diseases, their functional evolution, and provide key information on the genetic basis of left/right patterning defects known as heterotaxy.