Chris Q. Doe

Biosketch

We investigate the generation of neuronal diversity and neural circuit formation in Drosophila and mouse. More specifically, our current focus is on characterizing genes that regulate temporal identity within Drosophila neural stem cell lineages, identifying mechanisms of neural circuit formation for Drosophila larval locomotion, and identifying and characterizing lamina-specific genes that are required for neural circuit formation and function in the mouse visual cortex. In addition, we have developed a novel chemical/genetic intersectional system for purifying newly-transcribed RNA from specific cell types within tissues or organisms; we have used this approach successfully in both Drosophila and mouse. I consider mentorship an essential part of my job. I have mentored over 20 postdoctoral fellows in my lab, and an equal number as co-mentors for younger faculty member labs. I take mentoring seriously and work with postdoctoral fellows to develop a career development plan that will help them achieve their goals; I help them hone their paper and grant writing skills; I provide feedback on producing a compelling presentation; and even after they have started their own lab I provide guidance on navigating the challenges of running lab.

Research Interests

The establishment of Drosophila neural progenitors as a model for studying stem cell self-renewal, spindle orientation, and asymmetric cell division. Our findings are relevant to mammalian studies of tissue specific progenitors due to the evolutionary conservation of basic mechanisms.

Development of the "TU-tagging" system for chemical-genetic labeling of newly-transcribed RNA from specific cell types within intact tissues without cell purification. We pioneered this method in Drosophila but more recently have adapted it for use in mice. We have made both Cre-inducible and tTA-inducible transgenic lines for purifying RNA from any cell type that expresses a Cre or tTA transgene.

Temporal patterning within progenitor lineages, in which "temporal transcription factors" (TTFs) are sequentially expressed by progenitors as they go through their lineage, resulting in the diversification of neuronal identity. We identified two different TTF cascades in embryonic and larval progenitors, determined the cross-regulatory relationship within each TTF cascade, showed that the embryonic TTF cascade was required for generating pioneer neuron identity in multiple progenitors. We also identified a
novel mechanism of "progressive restriction in progenitor competence" that involves movement of specific loci to the nuclear envelope during progenitor lineages.

Development of larval locomotor circuits, including quantitative kinematics of motor/muscle activity, generation of tools to functionally manipulate small pools of interneurons, and identification of Eve+ interneurons that are required to maintain left-right balanced motor drive.