The function and regulation of the bHLH gene, cato, in Drosophila neurogenesis

BMC Developmental Biology, Mar 2010

Background bHLH transcription factors play many roles in neural development. cousin of atonal (cato) encodes one such factor that is expressed widely in the developing sensory nervous system of Drosophila. However, nothing definitive was known of its function owing to the lack of specific mutations. Results We characterised the expression pattern of cato in detail using newly raised antibodies and GFP reporter gene constructs. Expression is predominantly in sensory lineages that depend on the atonal and amos proneural genes. In lineages that depend on the scute proneural gene, cato is expressed later and seems to be particularly associated with the type II neurons. Consistent with this, we find evidence that cato is a direct target gene of Atonal and Amos, but not of Scute. We generated two specific mutations of cato. Mutant embryos show several defects in chordotonal sensory lineages, most notably the duplication of the sensory neuron, which appears to be caused by an extra cell division. In addition, we show that cato is required to form the single chordotonal organ that persists in atonal mutant embryos. Conclusions We conclude that although widely expressed in the developing PNS, cato is expressed and regulated very differently in different sensory lineages. Mutant phenotypes correlate with cato's major expression in the chordotonal sensory lineage. In these cells, we propose that it plays roles in sense organ precursor maintenance and/or identity, and in controlling the number of cell divisions in the neuronal branch of the lineage arising from these precursors.

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The function and regulation of the bHLH gene, cato, in Drosophila neurogenesis

Lage and Jarman BMC Developmental Biology The function and regulation of the bHLH gene, cato, in Drosophila neurogenesis Petra I zur Lage 0 Andrew P Jarman 0 0 Centre for Integrative Physiology, School of Biomedical Sciences, University of Edinburgh , Edinburgh EH8 9XD , UK Background: bHLH transcription factors play many roles in neural development. cousin of atonal (cato) encodes one such factor that is expressed widely in the developing sensory nervous system of Drosophila. However, nothing definitive was known of its function owing to the lack of specific mutations. Results: We characterised the expression pattern of cato in detail using newly raised antibodies and GFP reporter gene constructs. Expression is predominantly in sensory lineages that depend on the atonal and amos proneural genes. In lineages that depend on the scute proneural gene, cato is expressed later and seems to be particularly associated with the type II neurons. Consistent with this, we find evidence that cato is a direct target gene of Atonal and Amos, but not of Scute. We generated two specific mutations of cato. Mutant embryos show several defects in chordotonal sensory lineages, most notably the duplication of the sensory neuron, which appears to be caused by an extra cell division. In addition, we show that cato is required to form the single chordotonal organ that persists in atonal mutant embryos. Conclusions: We conclude that although widely expressed in the developing PNS, cato is expressed and regulated very differently in different sensory lineages. Mutant phenotypes correlate with cato's major expression in the chordotonal sensory lineage. In these cells, we propose that it plays roles in sense organ precursor maintenance and/or identity, and in controlling the number of cell divisions in the neuronal branch of the lineage arising from these precursors. - Background Basic-helix-loop-helix (bHLH) transcription factors are central to neurogenesis in metazoans [1]. The most well known role for such factors in neurogenesis is the socalled proneural function. This function underlies the commitment of neuroectodermal cells to a neural fate, and the term comes originally from the study of proneural genes in Drosophila. In this organism, proneural genes include atonal (ato), amos, scute (sc), and achaete (ac) which are required for the specification of sense organ precursors (SOPs) of the peripheral nervous system [2]. In mutations of these genes, specific subsets of SOPs fail to be formed. For instance, ato is required for the formation of SOPs of chordotonal (Ch) proprioceptive sensory organs [3]. Other members of the bHLH protein family are expressed after neural commitment and play a variety of roles in neural cells leading up to neural differentiation. This is particularly apparent in vertebrates, where for instance the factors NeuroM and NeuroD are required for neuronal migration and differentiation respectively [4,5]. In Drosophila, such downstream neural bHLH factors are represented by asense (ase), cousin of atonal (cato), deadpan (dpn) and target of poxn (tap). These genes are related to sc, ato, hairy/E(spl) and neurogenin respectively. ase, cato and dpn are widely expressed in developing neurons [6-8], whereas tap expression is confined to a small subset of sensory neurons [9]. The functions of these genes are less well known compared with proneural genes. ase is expressed in all neural precursors of both the CNS and PNS [6]. Mutations of ase result in reduced viability but mutant embryos exhibit only subtle PNS defects [10]. In the larval optic lobes, ase participates in the control of mitotic activity in neural precursors [11]. In this process, ase limits proliferation by antagonising dpn. In turn, dpn antagonises dacapo (dap) [12-14]. dap encodes a p21 cyclindependent kinase (CDK) inhibitor that is expressed transiently in cells prior to their terminal cell division in order to prevent further divisions [12-14]. Unlike ase and dpn, the expression of cato is confined to the developing PNS, where it was reported to be expressed in all SOPs and their progeny [7]. The function of cato is poorly known. Examination of embryos bearing large deficiencies of the cato region suggested a role in sensory neuron differentiation [7]. We report here the generation and analysis of specific cato mutations. Flies homozygous for cato loss-of-function mutations are viable. Mutant embryos show no gross neuronal differentiation defects, but have a defect in cell proliferation within the Ch sensory lineages. Combination of cato mutation with those of ato and ase reveals a second role for cato in the maintenance of Ch SOP fate or survival. Results Expression of Cato differs in Ato/Amos and Sc lineages It was previously reported that cato mRNA was initially activated in Ch SOPs, and subsequently it appeared to be expressed generally in all cells of the sensory PNS (both ato-dependent Ch cells and sc-dependent External Sensory (ES (...truncated)


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Petra I zur Lage, Andrew P Jarman. The function and regulation of the bHLH gene, cato, in Drosophila neurogenesis, BMC Developmental Biology, 2010, pp. 34, 10, DOI: 10.1186/1471-213X-10-34