Abstract |
Hey proteins are transcription factors that belong to the basic helix-loop-helix ‘Orange’ (bHLH-O)
protein group and they are often effectors of the Notch signaling pathway. Although extensive studies
about them have been done in mammalian, little is known about the role of their single orthologue in
Drosophila so far. Briefly, Drosophila Hey gene has been characterized as one of the alternative
neuronal fate determinants in the developing CNS. Its expression and function in the majority of
neuronal lineages is dependent on Notch signaling although few case of Notch independent expression
have been described. It has been, also, characterized as identity guardian of the fully differentiated
enterocytes in the adult fly midgut independently of Notch. We have studied its expression and
functional role in the developing midgut of Drosophila. Unlike its expression pattern in adult fly, we
detected Hey mainly in entero-endocrine cell population of the embryonic and larval midgut. In this
developmental context, Hey is a direct target of Notch signalling, revealing a novel Notch event in the
midgut development. Hey expression seems to follow every entero- endocrine generation wave
throughout embryonic and larval life. Furthermore, functional analysis has demonstrated its high
association with enteroendocrine fate and maintenance, while a few indications support its putative
connection with the development of adult midgut precursors, the population which gives rise to the
adult intestinal stem cells. Moreover, in a regulatory analysis context, we deleted the region of the
intronic enhancer located in the endogenous sequence of Drosophila melanogaster Hey gene. Viable
flies in homozygosity for the mutant Hey allele have shown a redundancy of Hey regulatory elements.
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