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Title: Characterization of enteric nervous system progenitors during embryognesis
Author: Lasrado, Reena
Awarding Body: Open University
Current Institution: Open University
Date of Award: 2013
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The mammalian Enteric Nervous System (ENS) is a complex assembly of enteric neurons and glia into discrete ganglia. Orchestrated mechanisms that control migration, proliferation, survival and differentiation of ENS progenitors in a spatio-temporal manner are essential to develop the functional complexity of the mature ENS. Although, considerable mechanistic insight into cellular processes that control ENS development has been achieved, by studying populations of ENS progenitors, several questions regarding the complex organization of the ENS network remain unanswered. In light of the complexity of the ENS, it is imperative to characterize ENS progenitors and their progeny at single-cell resolution. By developing and using a repertoire of genetic tools (Sox10-iCreERT2 ; R26R-YFP, Sox10iCreERT2 ; R26R-Confetti, Soxl0-Cre; R26R-MADM) we addressed the developmental potential and dynamic in vivo properties of individual ENS progenitors. Our strategies allowed us to identify and study the derivatives of individual Sox10+ ENS progenitors. Clonal strategies employed demonstrated that labelled daughter cells expand with symmetric potential. Further, embryonic cell fate analysis identified two pools of precursors within the ENS namely, fate-restricted and multi- lineage. Study of neuronal trajectory patterns of individual enteric neurons during embryogenesis, identified a temporal sequence in the appearance of the caudal, circumferential and oral projections. Additionally, an unique pairing pattern and differential trajectory behaviour of clonally- related neurons was evident. Using MADM, we identified phenotypic glial heterogeneity in the adult ENS. This single-cell resolution allowed us to define the morphology and locations of the different enteric 91ia subtypes. Finally, genetic single-cell manipulation of the Ret locus, critical for ENS development, revealed a new role for the Ret receptor in enteric glial differentiation. Overall, our data identifies important features of ENS progenitors and provides a platform for understanding the principles of organization of the complex ENS network and the maintenance of homeostasis in the adult ENS.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available