The role of Gremlin 1 in Xenopus neural crest induction

Student thesis: Doctoral ThesisDoctor of Philosophy

Abstract

Gremlin 1 (Grem1) is a member of the Dan family of secreted bone morphogenetic protein (BMP) antagonists. Originally identified in Xenopus laevis as an axis-inducing factor, it is endogenously expressed in the neural crest, but its role in the development of this important cell population is unclear. BMP signalling is known to be a key player in neural crest induction with levels intermediate to those in prospective neural plate and non-neural ectoderm acting in concert with Wnt activation at the neural plate border. This thesis investigates the role of Grem1 in neural crest induction by gain and loss of function approaches. Overexpression causes expansion of the neural crest, as well as the neural plate and neural plate border, while knockdown causes loss of neural crest and loss of the neural plate border marker msx1. Grem1 is regulated extracellularly by heparan sulfate proteoglycans (HSPGs), a class of cell surface and extracellular matrix macromolecules known to affect the distribution and availability of signalling proteins, and to modulate their activity at the plasma membrane. Three mutant Grem1 constructs with reduced HSPG binding were used to test their impact on its function in vivo. HSPG binding is required for its axis-inducing activity and for the induction of neural crest by Grem1. However, the induction of neural plate border markers appears to be unaffected. Overall this demonstrates a novel requirement for Grem1 in neural crest induction in a two-step process that is initially independent but later dependent on HSPG binding.
Date of Award2019
Original languageEnglish
Awarding Institution
  • King's College London
SupervisorEsther Bell (Supervisor) & Karen Liu (Supervisor)

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