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An important question in developmental biology is that how axial patterning genes work with growth and patterning to form any three-dimensional organ. In any multicellular organism, Organogenesis, requires axial patterning i.e. formation of Antero-Posterior (AP), Dorso-Ventral (DV), Proximo-Distal (PD) axes. Any deviation in these axes during development leads to genetic birth defects. We use Drosophila melanogaster (a.k.a fruit fly), eye as our model. As the genetic machinery between flies and human is conserved, any insights generated in flies can be extrapolated into humans. In Drosophila, DV patterning marks first lineage restriction event where expression of dorsal, ventral fate selectors forms dorsal & ventral compartments in eye respectively. We have identified defective proventriculus (dve), an ortholog of SATB homeobox 1 (in humans), as a new member of DV patterning gene hierarchy. Our previous data establishes dorsal gene hierarchy & states that dve acts downstream of pannier (pnr, GATA-1 transcription factor), and upstream of Wingless (wg), Loss-of-function of both dve or pnr results in dramatic dorsal eye enlargements. Furthermore, Wingless, also exhibits similar eye enlargement phenotypes and has also been shown to play a role in growth. Our data also suggests that Wg is downstream target of Hippo pathway (highly conserved) and that the pathway promotes cell differentiation by downregulating wingless. Hereby, I propose to investigate the role of dve and pnr in growth and patterning during Drosophila eye development. I will test whether these two fundamental processes works independently or in coordination with each other to form an eye. The proposed study will help in elucidating how cell fate specification, pattern formation and growth are involved in organ formation. Our study will have significant bearing on developmental mechanisms, patterning events, growth regulation during organogenesis, and helps us in understanding the etiology of growth related birth defects in eye.

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Graduate Research

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Madhuri Kango-Singh, Amit Singh

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Role of axial patterning genes in growth regulation during eye development