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Signaling, transcription and transcript stability during early embryonic development of the leech, Helobdella robusta
by Gonsalves, Foster Casimir, PhD, UNIVERSITY OF CALIFORNIA, BERKELEY, 2006, 0 pages; 3253878
 

Abstract: Intercellular signaling plays a crucial role in development and homeostasis. Various signaling cascades have been identified to date and are known to be regulated at multiple levels. My work presented in this dissertation focuses on the regulation of the Notch signaling pathway during leech development. Spatiotemporal modulation of the evolutionarily conserved, intercellular Notch signaling pathway is important in the development of many animals. Examples include the regulation of neural-epidermal fate decisions in neurogenic ectoderm of Drosophila and somitogenesis in vertebrate presomitic mesoderm (PSM). In both these and most other cases, it appears that Notch-class transmembrane receptors are ubiquitously expressed. Modulation of the pathway is achieved primarily by the localized expression of the activating ligand or by alteration of receptor specificity through a glycosyl transferase. In contrast, my work presented here shows that the abundance of the Notch-class mRNA itself is dynamically regulated. By taking the advantage of the long cell cycle of the 2-cell stage embryo of the leech Helobdella robusta, I show that this regulation is achieved at the level of transcript stability, as well as transcription. Moreover, MAPK signaling plays a significant role in regulating accumulation of the transcript by virtue of its effect on mRNA stability. Intracellular injection of heterologous reporter mRNAs shows that the Hro-notch 3' UTR, containing 7 A&barbelow;U R&barbelow;ich E&barbelow;lements (AREs), is key to regulating transcript stability. Thus the regulation of the Notch pathway can occur at a previously underappreciated level, namely that of transcript stability. Given that AREs occur in the 3' UTR of Notch-class genes in Drosophila, human and C. elegans, regulation of Notch signaling by modulation of mRNA levels may be operating in other animals as well. Furthermore, the dynamic expression of Notch during the 2-cell stage of the developing leech embryo seems to be crucial in regulating a developmental event that occurs several hours later, viz: the transition from cleavage type divisions to teloblastic divisions.

 
Advisor: Weisblat, David A.
School: UNIVERSITY OF CALIFORNIA, BERKELEY
Source: DAI-B 68/02, p. 708, Aug 2007
Source Type: PhD
Subjects: Neurology; Cellular biology
Publication Number: 3253878
     
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