Student Theses and Dissertations

Date of Award

2007

Document Type

Thesis

RU Laboratory

Hatten Laboratory

Keywords

cerebellar neurogenesis, purkinje cells, cerebellar nuclei, cerebellar cortex

Abstract

The cerebellum is comprised of an overlying cortical structure and a basal set of cerebellar nuclei (CN). The cerebellar cortex contains two principal neurons, the Purkinje cell (PC) and the granule cell (GC), whereas the CN are formed by an heterogeneous array of cerebellar nuclei neurons. Although granule cell development is well-studied, the specification and early migratory routes of cerebellar nuclei neurons and Purkinje cells are not well understood. To map neural progenitor identity, we analyzed the expression of various members of the TALE, LIM and bHLH transcription factor families in the avian and murine cerebellar anlagen. We show here that the combinatorial expression of transcription factors Irx3, Meis1, Meis2, and Lhx2/9 defines neurons of the CN, and that the combinatorial expression of Lhx1 and Lhx5 defines Purkinje cells, as these distinct neural classes exit the cell cycle. We also show that Meis1 is a new marker for granule cell progenitors. Remarkably, the onset of transcription factor expression follows a precise temporal sequence, in concert with the emergence of these three classes of cerebellar neurons. In addition, this study provides direct visualization of precursors of both the CN (Irx3+, Meis1/2+) and PC (Lhx1/5+) moving along RC2/BLBP+ radial glial fibers in their transit from the ventricular zone (VZ) to the differentiating mantle zone. As cerebellar histogenesis proceeds, granule cell progenitors (Meis1+/Math1+) form the external granule layer and cerebellar nuclei neurons (Irx3+/Meis1+/Meis2+) migrate circumferentially off the surface to settle as distinct nuclei underneath the emerging cerebellar cortex at early postnatal development. Thus, this transcription factor profile identifies the precursors of cerebellar nuclei neurons, Purkinje cells and granule cells from embryonic neurogenesis throughout postnatal stages, and provides a detailed spatiotemporal map of the morphogenetic events that form the cerebellar nuclei and the overlying cerebellar cortex.

Comments

A thesis presented to the faculty of The Rockefeller University in partial fulfillment of the requirements for the degree of Doctor of Philosophy.

Permanent URL

http://hdl.handle.net/10209/131

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