Early lineage decisions during mouse gastrulation (360G-Wellcome-109098_Z_15_A)

£45,812

Diversification of mesoderm and endoderm subtypes occurs at the outset of mouse gastrulation as epiblast cells migrate through the primitive streak (PS). The underlying inductive signals, gene-regulatory networks, and epigenetic modifications that direct lineage diversification at this early stage remains ill-defined. The aim of this project is to dissect the molecular mechanisms that underpin cell fate diversification, as cells egress the PS, by investigating the function of T-box transcription factors (TF), Eomesodermin (Eomes) and Brachyury (T). Eomes and T are expressed in the PS and Eomes is required for specification of cardiac mesoderm (CM) and definitive endoderm (DE). Single cell lineage tracing and RNA-seq experiments will be completed to define the potency and heterogeneity of Eomes and T expressing progenitors. The functional role Eomes plays in haematopoiesis will also be investigated using multiple gain and loss of function experiments. Finally, we will investigate context dependent Eomes binding sites and interacting partners. Eomes tagged mouse embryonic stem cells (mESC) will be differentiated into CM or DE progenitors and with them we will perform ChIP-Seq, RNA-Seq and immunoprecipitation-mass spectrometry(IP-MS). The experiments proposed will help resolve the functional and molecular roles T and Eomes play during early stages of lineage diversification.

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Grant Details

Amount Awarded 45812
Applicant Surname Harland
Approval Committee Internal Decision Panel
Award Date 2017-01-31T00:00:00+00:00
Financial Year 2016/17
Grant Programme: Title PhD Studentship (Basic)
Internal ID 109098/Z/15/A
Lead Applicant Mr Luke Harland
Partnership Value 45812
Planned Dates: End Date 2019-10-01T00:00:00+00:00
Planned Dates: Start Date 2016-10-01T00:00:00+00:00
Recipient Org: Country United Kingdom
Region South East