A carregar...
Publicação
Characterization of the hormonal regulation of Drosophila Neural Stem cells during brain development
| Nome: | Descrição: | Tamanho: | Formato: | |
|---|---|---|---|---|
| 6.5 MB | Adobe PDF |
Autores
Orientador(es)
Resumo(s)
Abstract
Organ growth and developmental progression requires regulation at different levels, from the
molecular level to the cellular level within tissues, to the systemic level within organisms. The
modulation of growth rate is intricately linked to an organism's physiological state, with hormones
playing a pivotal role as essential regulatory molecules. Hormones not only modulate development
but also orchestrate the physiological responses to the external environment.
Stem cells are responsible for originating all the cell types of all the tissues in the organism and must
therefore also be modulated in response to physiological changes to keep pace with changing
demands of development. However, the mechanisms by which stem cell function is systemically
regulated is still poorly understood. Although it has been described for some time that stem cells
respond to hormonal signals, the extent to which this regulation occurs and how is integrated with
the overall organism development remains to be understood.
In this project I use the model of Drosophila melanogaster neural stem cells to understand how
hormonal signals directly or indirectly regulate stem cell proliferation and how this regulation is
integrated at the physiological level during development.
In Chapter I, I demonstrate that the steroid hormone ecdysone plays a multi-step, stage specific role
in regulating Drosophila neuroblasts. By genetically manipulating the synthesis of this hormone, I
show that the developmental milestone called “critical weight peak”, the peak that informs the body
has reached minimum viable weight to survive metamorphosis, acts as checkpoint necessary to set
neuroblast cell cycle pace during larval neurogenesis. The peaks of ecdysone that occur post-critical
weight are no longer required to maintain neuroblast division rate. I additionally show that in a
second time point, at the onset of pupariation, ecdysone is instead required to trigger neuroblast’s
proliferation exit and consequently the end of neurogenesis. I demonstrate that without this signal
from ecdysone, neuroblasts lose their ability to exit proliferation. Interestingly, although these
neuroblasts proliferate for a longer period, the number of differentiated neurons is smaller
compared to wild-type brains, suggesting a role for ecdysone in neuron maintenance.
In Chapter II I show that, during prepupal development, the phenomenon of fat body migration to
the head space of the animal is required to provide the brain with lipids, an interorgan cue required
for timely neuroblast decommission. These results demonstrate that neuroblasts do not have sufficient cell-autonomous information about their decommission timing and require not only local
but interorgan communication to regulate their proliferation.
Overall, this study provides insights into how neural stem cells coordinate their division rate with
the pace of body growth through ecdysone hormonal regulation, identifying a novel coordination
mechanism between animal development and neural stem cell proliferation. Furthermore, it
identifies the fat body as a novel player in neural stem cell regulation and sheds light on how
interorgan communication is perceived at the cellular level to coordinate brain formation with
organism development.
Descrição
Palavras-chave
Hormonal regulation Drosophila Neural Stem cells Brain