Proneural bHLH: cell population dynamics in mouse retina

• Author(s): Miragaia, Ricardo Júdice, 1988-
• Date: 2011
• Persistent ID: http://hdl.handle.net/10451/6468
• Origin: Repositório da Universidade de Lisboa
• Subject(s): Embriologia molecular; Retina; Sinalização Notch; Diferenciação celular; Teses de mestrado - 2011
• Document Type: Master Thesis
• Language: English
• Advisor(s): Gaspar, Cláudia; Zilhão, Rita, 1959-

Description

Tese de mestrado. Biologia (Biologia Molecular e Genética). Universidade de Lisboa, Faculdade de Ciências, 2011 The simultaneous production of several cell-types during embryonic development of the retina was previously shown to be regulated by the Notch-signaling pathway at multiple levels, through the sequential expression of two Notch ligands, Dll1 and Dll4. While Dll1 activity has been shown to be responsible for progenitor maintenance, Dll4 function has not been addressed until now, although a role in the regulation of cell-fate acquisition and celldiversity had been suggested. To address the role of Dll4 in the developing retina, we first characterized the intrinsic differentiation potential of Dll4-expressing cells during the first wave of retinal differentiation, at E13.5, by comparing its expression with that of three bHLH-encoding genes (Ngn2, Math5 and NeuroD), whose combined expression identify different retinal progenitors. Taking advantage of a Dll4 conditional knock-out (Dll4 cKO) mouse strain, we have used the expression of the same set of genes to evaluate the effects caused by Dll4 deletion on the profile of the differentiating population of cells. Our analysis of Dll4-expressing cells has revealed that these are still multipotent, although heavily biased towards the photoreceptor fate. We have also found that Dll4 absence leads to an increase in the production of photoreceptor and amacrine cells. The present work has allowed us to propose that during the first wave of differentiation Dll4-mediated Notchsignaling inhibits photoreceptor and amacrine cell production through inhibition of Ngn2 and NeuroD in the surrounding cells.