The Krüppel-Like Factor Dar1 Determines Multipolar Neuron Morphology.

Neurons typically assume multipolar, bipolar, or unipolar morphologies. Little is known about the mechanisms underlying the development of these basic morphological types. Here, we show that the Krüppel-like transcription factor Dar1 determines the multipolar morphology of postmitotic neurons in Drosophila. Dar1 is specifically expressed in multipolar neurons and loss of dar1 gradually converts multipolar neurons into the bipolar or unipolar morphology without changing neuronal identity. Conversely, misexpression of Dar1 or its mammalian homolog in unipolar and bipolar neurons causes them to assume multipolar morphologies. Dar1 regulates the expression of several dynein genes and nuclear distribution protein C (nudC), which is an essential component of a specialized dynein complex that positions the nucleus in a cell. We further show that these genes are required for Dar1-induced multipolar neuron morphology. Dar1 likely functions as a terminal selector gene for the basic layout of neuron morphology by regulating both dendrite extension and the dendrite-nucleus coupling. SIGNIFICANCE STATEMENT: The three basic morphological types of neurons--unipolar, bipolar, and multipolar--are important for information processing and wiring of neural circuits. Little progress has been made toward understanding the molecular and cellular programs that generate these types since their discovery over a century ago. It is generally assumed that basic morphological types of neurons are determined by the number of dendrites growing out from the cell body. Here, we show that this model alone is insufficient. We introduce the positioning of nucleus as a critical factor in this process and report that the transcription factor Dar1 determines multipolar neuron morphology in postmitotic neurons by regulating genes involved in nuclear positioning.