title: Roles of Drosophila Kruppel-homolog 1 in neuronal morphogenesis.
abstract: The molecular mechanisms underlying remodeling of neural networks remain largely unknown. In Drosophila, widespread neural remodeling occurs during metamorphosis, and is regulated by ecdysone. Kruppel-homolog 1 (Kr-h1) is a zinc finger transcription factor known to play a role in orchestrating ecdysone-regulated transcriptional pathways and, furthermore, implicated in governing axon morphogenesis. Interestingly, in honey bee workers, neural expression of the Apis mellifera homolog of Kr-h1 is enhanced during their transition to foraging behavior when there is increased neurite outgrowth, branching, and synapse formation. Here, we assessed the role(s) of KR-H1 in Drosophila neuronal remodeling and morphology. We characterized the effect of Kr-h1 expression on neuronal morphology through Drosophila larval, pupal, and adult stages. Increased expression of Kr-h1 led to reduced branching in individual neurons and gross morphological changes in the mushroom bodies (MBs), while knocking down Kr-h1 did not produce any obvious changes in neural morphology. Drosophila Kr-h1 is normally expressed when MB neurons do not undergo active morphogenesis, suggesting that it may play a role in inhibiting morphogenesis. Further, loss of endogenous KR-H1 enhanced the neuronal morphogenesis that is otherwise delayed due to defective TGF-beta signaling. However, loss of KR-H1 alone did not affect neuronal morphogenesis. In addition, Kr-h1 expression remains strongly linked to ecdysone-regulated pathways: Kr-h1 expression is regulated by usp, which dimerizes to the ecdysone receptor, and Kr-h1 expression is essential for proper patterning of the ecdysone receptor isoforms in the late larval central nervous system. Thus, although KR-H1 has a potential for modulating neuronal morphogenesis, it appears physiologically involved in coordinating general ecdysone signaling.
authors.affiliation: Department of Neurobiology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
authors.forename: Lei
authors.initials: L
authors.lastname: Shi
authors.forename: Suewei
authors.initials: S
authors.lastname: Lin
authors.forename: Yelena
authors.initials: Y
authors.lastname: Grinberg
authors.forename: Yannick
authors.initials: Y
authors.lastname: Beck
authors.forename: Christina M
authors.initials: CM
authors.lastname: Grozinger
authors.forename: Gene E
authors.initials: GE
authors.lastname: Robinson
authors.forename: Tzumin
authors.initials: T
authors.lastname: Lee
mesh_terms: D000818:Animals; D019521:Body Patterning / Q000502:physiology; D001921:Brain / Q000196:embryology* / Q000378:metabolism; D004330:Drosophila; D029721:Drosophila Proteins / Q000378:metabolism*; D004440:Ecdysone / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D007150:Immunohistochemistry; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism*; D007814:Larva; D008675:Metamorphosis, Biological; D018613:Microscopy, Confocal; D009024:Morphogenesis; D009030:Mosaicism; D024521:Mushroom Bodies / Q000196:embryology / Q000378:metabolism; D009474:Neurons / Q000166:cytology* / Q000378:metabolism*; D011679:Pupa
chemical_list: D029721:Drosophila Proteins; C497242:Kr-h1 protein, Drosophila; D051741:Kruppel-Like Transcription Factors; D004440:Ecdysone