Genetic Basis of Patterning and Growth in Drosophila Eye - In multi-cellular organisms, axial patterning is required for transition of a mono-layered epithelium of an organ
primordium to a three-dimensional organ by delineation of antero-posterior (AP), dorso-ventral (DV), and
proximo-distal (PD) axis. We employ Drosophila melanogaster (fruit fly) eye model to study the highly
conserved fundamental process of (axial) DV patterning and growth. During eye development, DV patterning
precedes AP and PD axis patterning, and forms dorsal and ventral compartments. The border between the
dorsal and the ventral domains of eye, termed equator, is the site for upregulation of the Notch (N) signaling,
which regulates cell proliferation and differentiation. Discerning the mechanism of axes determination (DV) is
crucial for our understanding of organogenesis as the problems with DV delineation results in developmental/
birth defects in flies to humans. Our long term goal is to understand the genetic basis of DV patterning which
is established by interactions of the dorsal selector genes and the ventral genes. The Drosophila eye begins
from a ventral equivalent state on which the dorsal fate is established by onset of expression of GATA-family
transcription factor Pannier (Pnr), the secreted morphogen Wingless (Wg), and Iroquois (Iro-C) family proteins.
In the dorsal eye, pnr is not the sole regulator of Wg expression. It strongly suggests that there may be other
dorsal eye genes that are yet to be identified. To understand the molecular genetic basis of DV patterning,
we will analyze the (1) Determine the role of new dorsal eye gene dve during eye development, (2)
Investigate genetic hierarchy of dorsal eye patterning genes, and (3) Whether DV patterning and Hippo
signaling may co-regulate Wg during DV patterning.. Given that the genetic machinery is conserved, we
will also test the role of SATB1, a human ortholog of dve in the eye, which is known to be involved in growth
regulation, cancer and metastasis. These studies will help discern (a) a new role of dve in axial patterning and
complex process of retinal differentiation, (b) role of dve in delineating eye versus head boundary and (c)
genes involved in growth and cancer do have function in patterning and differentiation, (d) How do independent
pathways interact to regulate growth and patterning in the developing eye?. These studies will have significant
bearings on understanding the (i) molecular basis of developmental defects caused by mutations in the human
homolog of Drosophila dve, and (ii) genetic mechanism of early developmental events during organogenesis in
higher vertebrates too. In humans and other vertebrates, DV polarity of the retina regulate the retinal axon
projections to the brain. These studies will shed light on the role of early developmental events on the retinal
axon projection to the brain during normal development and disease. The knowledge generated from these
studies is expected to elucidate fundamental mechanisms in patterning and growth of normal visual function
and within the context of retinal disease and birth defects in the eye.
