Roles of Drosophila Kruppel-homolog 1 in neuronal morphogenesis
Department of Neurobiology
Medical Subject Headings
Animals; Body Patterning; Brain; Drosophila; Drosophila Proteins; Ecdysone; *Gene Expression Regulation, Developmental; Immunohistochemistry; Kruppel-Like Transcription Factors; Larva; Metamorphosis, Biological; Microscopy, Confocal; Morphogenesis; Mosaicism; Mushroom Bodies; Neurons; Pupa
Life Sciences | Medicine and Health Sciences | Neuroscience and Neurobiology
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.
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Citation: Dev Neurobiol. 2007 Oct;67(12):1614-26. Link to article on publisher's site