Analysis of the initial nerve connections in the embryonic vertebrate brain

  • Michelle Ware

Student thesis: Doctoral Thesis


The complex organisation of the vertebrate brain starts off as a simple arrangement of axon tracts in the early embryo termed the early axon scaffold. These initial axon tracts were important for the correct guidance of later, follower axons. Yet, little is known about the temporal and spatial control of neuronal differentiation, or the control of axon guidance for the early axon scaffold. The aim of this study was to provide a detailed anatomical description of the early axon scaffold as a basis for functional experiments, to identify candidate genes involved in the differentiation of the early neurones, and to gain insight into the axon guidance for a particular early tract.
The anatomical formation of the early axon scaffold in the chick embryonic brain has been analysed in detail using immunohistochemistry and axon tracing. The early tracts in the chick were directly compared with cat shark, Xenopus, zebra finch and mouse. These results highlight the conservation of early axon scaffold development. The medial longitudinal fascicle (MLF) was shown to be the most conserved tract forming first in all vertebrates, apart from mouse where it forms later. Since the genes involved in specification of neurones to an MLF fate are unknown, microarray analysis was used to identify candidate genes with a possible role in MLF neurone specification. CRABPI was shown by in situ hybridisation to be specifically expressed by the MLF neurones.
Another highly conserved early tract is the tract of the posterior commissure (TPC). Its neurones were shown to be located in the ventral diencephalon of the chick embryonic brain. While the TPC neurones were intermingled with the MLF neurones, their axons project along very separate paths, suggesting that their outgrowth is directed by different guidance cues present. Netrin1 and Netrin2 were identified as candidate genes for repelling the TPC axons along their correct path. Gain-of-function experiments led to reduction or loss of the TPC, suggesting that Netrins act as repellents on the TPC axons in the chick embryonic brain.
Date of AwardNov 2010
Original languageEnglish
Awarding Institution
  • University of Portsmouth
SupervisorFrank Schubert (Supervisor) & Colin Sharpe (Supervisor)

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