IDENTIFICATION OF TRANSCRIPTIONAL TARGETS OF THE HOMEODOMAIN TRANSCRIPTION FACTORS Ind AND Vnd
Tonia Von Ohlen, KSU Division of Biology

PROJECT SUMMARY
The Drosophila central nervous system (CNS) is composed of a complex array of motoneurons, interneurons and glia. Generation of the mature CNS is a two step process. First, positional cues across the anterior-posterior and dorsoventral (DV) axes act to specify neural stem cells called neuroblasts. Second, neuroblasts undergo stereotyped cell divisions to generate the precise complement of neuronal and glial cells that populate the mature CNS. There are three signaling pathways required to subdivide the neurectoderm in to three columns across the DV axis, these correspond to the domains of expression of three homeodomain proteins. From ventral to dorsal these are Ventral nervous system defective (Vnd), Intermediate neuroblasts defective (Ind) and Muscle segment homeobox (Msh). Each of these proteins is required for proper formation and/or specification of the corresponding neuroblasts from their respective column. The products of these genes play multiple important roles in formation and specification of the embryonic nervous system. Ind, for example, is known to play roles in two important processes. First, Ind is essential for formation of neuroblasts in conjunction with SoxB class transcription factors, which are known to specify neural stem cells in vertebrates. Second, Ind plays an important role in patterning the CNS in conjunction with other columnar hox genes, vnd and msh. This process is also similar to neural tube patterning in vertebrates. For example, the mouse homologs of Ind, Gsh1 and Gsh2, are expressed in intermediate regions of the neural tube. Gsh1 and Gsh2 are key regulators of interneuron and sensory interneuron cell fates in the mouse neural tube. Thus, characterizing how these genes function is of critical importance to understanding the basics of CNS formation in both Drosophila and humans. Because Ind is a homeodomain protein it is predicted to be a transcriptional regulator. Therefore, Chromatin immunoprecipitation and state of the art sequencing techniques will be utilized to identify novel transcriptional targets.