The objective of this program is to identify and characterize transcription factor regulatory networks controlling cell-identity decisions in the developing central nervous system (CNS). During CNS development, stem cells undergo multiple rounds of asymmetric cell divisions, producing either neuronal or glial progenitor cells with each division. Underpinning the formation of stem cell lineages are integrated regulatory networks that establish distinct cellular identities and, ultimately, create unique neuronal/glial subtypes within their lineages. Although much is known about early developmental decision leading to the formation of neural stem cells, little is understood about subsequent cell fate decisions that generate the unique functional identities of neurons or glia. The identification and functional characterization of the molecules and pathways/circuits underlying these cell fate decisions remain a central goal of neurobiology. We have discovered that in the developing Drosophila CNS most, if not all, stem cells transition through a series of synchronized gene expression programs during their asymmetric divisions. These temporal windows of gene expression are marked by the sequential production of different transcription factors that in turn help establish unique neural cell types. Our studies have revealed that the temporal domains are part of a global CNS regulatory network that coordinates cell fate-determining events. Our studies have demonstrated that when cultured in isolation, Drosophila stem cells maintain the correct temporal shifts in transcription factor gene expression. This cellular independence provides evidence that once neural lineage development is initiated no additional signaling cues between stem cells or adjacent tissues are required to trigger this cascade of regulatory gene expression. Our work on the characterization of novel genes identified from a differential cDNA expression screen resulted in new insights into the regulatory genes controlling CNS development. In particular, analysis of the novel genes, Nerfin-1 and Nerfin-2, reveal that they belong to a highly conserved Zn-finger transcription factor gene subfamily with human and nematode cognates. Nerfin-1 is expressed in neural stem cells while Nerfin-2 is expressed in a subset of brain neurons. Functional analysis of nerfin-1 has revealed that its encoded protein is required for proper axon pathfinding in the CNS. Understanding neural cell-identity decisions will ultimately have significant implications for identifying and treating developmental defects. Given that many, if not most, of the genes employed to construct a functioning nervous system are highly conserved among metazoans, deciphering the regulatory logic of Drosophila CNS development will most certainly aid in our understanding of human development. Additional information and publications describing this work can be obtained at our web site (

Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Zip Code
Brody, Thomas; Yavatkar, Amarendra S; Park, Dong Sun et al. (2017) Flavivirus and Filovirus EvoPrinters: New alignment tools for the comparative analysis of viral evolution. PLoS Negl Trop Dis 11:e0005673
Ross, Jermaine; Kuzin, Alexander; Brody, Thomas et al. (2015) cis-regulatory analysis of the Drosophila pdm locus reveals a diversity of neural enhancers. BMC Genomics 16:700
Wang, Yu-Chun; Yang, Jacob S; Johnston, Rebecca et al. (2014) Drosophila intermediate neural progenitors produce lineage-dependent related series of diverse neurons. Development 141:253-8
Awasaki, Takeshi; Kao, Chih-Fei; Lee, Ying-Jou et al. (2014) Making Drosophila lineage-restricted drivers via patterned recombination in neuroblasts. Nat Neurosci 17:631-7
Matyi, S A; Dupre, J M; Johnson, W L et al. (2013) Isolation and characterization of Staphylococcus aureus strains from a Paso del Norte dairy. J Dairy Sci 96:3535-42
Kundu, Mukta; Kuzin, Alexander; Lin, Tzu-Yang et al. (2013) cis-regulatory complexity within a large non-coding region in the Drosophila genome. PLoS One 8:e60137
Brody, Thomas; Yavatkar, Amarendra S; Kuzin, Alexander et al. (2012) Use of a Drosophila genome-wide conserved sequence database to identify functionally related cis-regulatory enhancers. Dev Dyn 241:169-89
Roessler, Erich; Hu, Ping; Hong, Sung-Kook et al. (2012) Unique alterations of an ultraconserved non-coding element in the 3'UTR of ZIC2 in holoprosencephaly. PLoS One 7:e39026
Kuzin, Alexander; Kundu, Mukta; Ross, Jermaine et al. (2012) The cis-regulatory dynamics of the Drosophila CNS determinant castor are controlled by multiple sub-pattern enhancers. Gene Expr Patterns 12:261-72
Kuzin, Alexander; Kundu, Mukta; Brody, Thomas et al. (2011) Functional analysis of conserved sequences within a temporally restricted neural precursor cell enhancer. Mech Dev 128:165-77

Showing the most recent 10 out of 11 publications