National Circuit Assembly :: Assembly

National Circuit Assembly


We are interested in the basic mechanisms of neural development. Our strategy is to use the relatively simple Drosophila peripheral nervous system (PNS) to discover the genetic program that controls its development. In doing so, we hope to uncover evolutionarily conserved core programs that control different steps of neural development in animals. We started with the earliest steps in neural development (neurogenesis and neuronal cell fate specification) and gradually worked our way toward later steps (neuronal morphogenesis and the assembly of a functional neuronal circuit).

Some highlights of our earlier efforts include the discoveries of atonal and numb. Atonal is a basic helix-loop-helix (bHLH) protein, which is the founding member of an important family of proneural genes that initiate the development of two major types of sensory neurons used in vision and hearing. Its mammalian homologs include Neurogenin, Math1, and Math5. During asymmetric cell division, numb functions as a cell fate determinant. Numb provided a starting point for the study of asymmetric cell division in Drosophila and vertebrates, which led to insights into the molecular basis of asymmetric cell division. In recent years, the major focus of our lab has shifted to the study of dendrite development and neuronal circuit assembly.

Mechanisms Controlling Dendrite Development in Drosophila
Dendrite arborization patterns are critical determinants of neural circuit formation and influence the type of synaptic or sensory inputs a neuron is able to receive. Moreover, dendrite defects are associated with a variety of human mental disorders such as autism. Relatively little is known about the molecular mechanisms that control dendrite development. We use the fly transgenic technique to express green fluorescent protein (GFP) in the dendritic arborization (da) neurons, a group of sensory neurons with a stereotyped dendritic branching pattern. This allows us to visualize the development of the dendrites of da neurons in living fly embryos and to use them as an assay system for a genetic dissection of neuronal polarity and dendrite development. We have gained insights about the mechanisms underlying (1) how axons and dendrites are made differently, (2) how a neuron acquires its neuronal type-specific morphology, (3) how the dendrites of different neurons are organized, (4) how the size of a dendritic arbor is controlled, and (5) how the pruning and remodeling of dendrites are regulated during development.

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