# Genomic and Genetic Dissection of Hematopoietic Development in Drosophila

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2023 · $433,009

## Abstract

PROJECT SUMMARY/ABSTRACT
Elucidation of the genetic and molecular mechanisms that underlie normal blood cell development is an
important prerequisite for understanding and treating hematopoietic disorders such as leukemias. Drosophila
has proven to be an extremely powerful system for genetic dissection of such mechanisms, which are
remarkably conserved in mammals. This study uses the excellent genetic tools available in Drosophila to
address specific questions related to how the balance between progenitors and differentiated cells is achieved.
Preliminary data suggests that the tight coupling between cell-cycle regulation and differentiation pathways in
progenitors plays an important role in determining the balance of progenitors and differentiated cells. In
addition, two signals that originate in distinct transitory populations define parallel paths of hematopoietic
development, and we hypothesize that they subsequently affect the balance between progenitor maintenance
and differentiation that is crucial for homeostasis. These mechanisms will be explored in three aims. In Aim 1,
a thorough genetic analysis will be aimed towards obtaining evidence for the spatiotemporal developmental
mechanisms that generate parallel paths in hematopoiesis. The genetic data will be fully integrated
with transcriptomic analysis to determine how the system generates lineage biases in cells with related, but
not identical transcriptomes. In Aim 2, the signals that distinguish the two transitory populations will be
explored as will the downstream effects of these signals on the balance between progenitor maintenance and
differentiation. This will involve the genetic dissection of a JNK-related and a PVR-related signal that are
unique attributes of each transitory population. Lastly, in Aim 3, a genetic/functional analysis of integrated Hh-
and Wnt6-dependent pathways that control the balance between cell proliferation and differentiation will be
investigated. The role of Wnt6 in controlling cell growth and oxidative status of the progenitors will be tested to
obtain a mechanistic understanding of how and why the control of cell cycle and differentiation are closely and
directly linked to each other. Overall, the proposed research will yield important insights into the fundamental
mechanisms that govern the balance between the opposing forces of progenitor maintenance and
differentiation in blood cell development. As these pathways are conserved in humans, this analysis will help
bridge the gap between broadly available descriptions of genetic control during hematopoiesis with the less
well-defined in vivo functional relevance of such genetic networks to the controlled process of hematopoiesis
during homeostatic conditions and the genetic perturbations that lead to blood disorders. These experiments,
done in the Drosophila model, will further our understanding of, and provide guidance for, future analysis of
blood development and disorders in humans.

## Key facts

- **NIH application ID:** 10650410
- **Project number:** 5R01HL067395-19
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** UTPAL BANERJEE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $433,009
- **Award type:** 5
- **Project period:** 2001-05-10 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10650410

## Citation

> US National Institutes of Health, RePORTER application 10650410, Genomic and Genetic Dissection of Hematopoietic Development in Drosophila (5R01HL067395-19). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10650410. Licensed CC0.

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