The long term goal of my group is to understand the development and patterning of central nervous system (CNS) using model organism Drosophila melanogaster (fruit fly). The short life span (10 days) and the wealth of genetic tools and reagents available in Drosophila make it a particularly attractive model system to study this problem.
The bilaterian body plan is comprised of three axes: the anterior-posterior axis (AP axis), the dorsal-ventral axis and the proximal-distal axis of the limb. The specification of the AP axis by Hox genes is one of the earliest steps in the development of an organism. Hox genes are a family of highly conserved homeodomain (HD) containing transcription factors which are responsible for giving unique identity to the segments of the body. There are 8 Hox genes in Drosophila and 39 Hox genes in vertebrates (divided into 4 clusters) as shown in Figure-1.
Hox proteins are known to often function with two other HD-containing transcription factors: Extradenticle (Exd in Drosophila; Pbx in vertebrates) and Homothorax (Hth in Drosophila and Meis in vertebrates).
Both in Drosophila vertebrates, Hox genes are known to express in the central nervous system (CNS) where they play a role in AP axis determination (Figure-2) but the molecular basis of the Hox function in CNS is not very well understood. For example, very few Hox targets genes and cofactors are known and characterized in CNS.
The key question is to address how Hox genes control proliferation and differentiation of neural stem cells (NSC) along the AP axis to pattern CNS. Current understanding in the field suggests a possible role for epigenetic regulation of Hox target genes to play an important role in the process; I intend to employ a multi-disciplinary approach to address this problem.
Since the underlying principles of CNS patterning are conserved across species and both mammalian and Drosophila NSCs have very similar molecular properties (like progressive lineage restriction, mitotic quiescence and asymmetric cell division), therefore the studies done in Drosophila will be relevant in a wider context.
For introductory developmental biology and AP axis specification in flies and vertebrates
Any standard developmental biology textbook is a good point to start, below I list a few:
The Chapter on developmental biology in “Molecular Biology of cell-by Bruce Alberts”
The chapter on Drosophila axis formation from “Principles of Development-by Lewis Wolpert” and “Developmental Biology-by Schott Gilbert”
The Making of a Fly: The Genetics of Animal Design, by Peter A. Lawrence
To learn about Drosophila development, go to http://flymove.uni-muenster.de/ click on processes tab, the website gives a concise and easy overview of fly development.
To know more about axis determination during central nervous system development
Reichert, H. A tripartite organization of the urbilaterian brain: developmental genetic evidence from Drosophila. Brain Res Bull 66, 491-494, (2005).
Maurange, C. & Gould, A. P. Brainy but not too brainy: starting and stopping neuroblast divisions in Drosophila. Trends Neurosci 28, 30-36 (2005).
Alexander, T., Nolte, C. & Krumlauf, R. Hox genes and segmentation of the hindbrain and axial skeleton. Annu Rev Cell Dev Biol 25, 431-456, (2009).
Working in this lab is subject to your clearing appropriate CDFD selection procedures (for details contact EMPC Section, CDFD: academiacdfd.org.in). At the moment there are no postdoctoral positions available but anyone interested is encouraged to get in touch.
A write up of 250 words explaining your specific academic interest in the lab is expected from everyone seeking to explore the possibility of working in this lab at any position. A prior knowledge in genetics and biochemistry will be advantageous but not a pre-requisite.