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To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ydbio.2007.04.011 Byline: Yu-Chen Tsai (a)(b), Jih-Guang Yao (a)(c), Po-Hao Chen (a)(b), James W. Posakony (d), Scott Barolo (d), Jaesob Kim (e), Y. Henry Sun (a)(c) Keywords: Upd/Jak/STAT signaling; Drosophila; Eye; Morphogenetic furrow initiation; wg repression Abstract: The initiation of retinal development in Drosophila begins at the posterior center (PC) of the eye disc margin. The front of the differentiation wave, recognized as a morphogentic furrow (MF), moves from posterior to anterior. What determines MF initiates from the specific PC site is still unclear. The unpaired (upd) gene is expressed at PC at early third instar, just before the time of MF initiation. Therefore, upd is expressed at the appropriate time and location for a specific role in defining the site of MF initiation. upd encodes a ligand for the Jak/STAT signaling pathway. In this report, we showed that the Upd/Jak/STAT signaling is required and sufficient to determine MF initiation. This is primarily achieved by repressing the transcription of wingless (wg), which is known to block MF initiation. Author Affiliation: (a) Institute of Molecular Biology, Academia Sinica, Nankang, Taipei, Taiwan, Republic of China (b) Department of Life Science Research Center, Tunghai University, Taichung, Taiwan, Republic of China (c) Institute of Genetics, National Yang-Ming University, Shipai, Taipei, Taiwan, Republic of China (d) Division of Biological Sciences, Section of Cell and Developmental Biology, University of California San Diego, La Jolla, CA 92093-0349, USA (e) Department of Biological Sciences, Korea Advanced Institute of Science and Technology, 373-1 Guseong-Dong, Yuseong-Gu, Daejeon 305-701, Korea Article History: Received 2 January 2007; Revised 8 April 2007; Accepted 11 April 2007

eyeless (ey) is a key regulator of the eye development pathway in Drosophila. Ectopic expression of ey can induce the expression of several eye-specification genes (eya, so, and dac) and induce eye formation in multiple locations on the body. However, ey does not induce eye formation everywhere where it is ectopically expressed, suggesting that EY needs to collaborate with additional factors for eye induction. We examined ectopic eye induction by EY in the wing disc and found that eye induction was spatially restricted to the posterior compartment and the anterior-posterior (A/P) compartmental border, suggesting a requirement for both HH and DPP signaling. Although EY in the anterior compartment induced dpp and dac, these were not sufficient for eye induction. Coexpression experiments show that EY needs to collaborate with high level of HH and DPP to induce ectopic eye formation. Ectopic eye formation also requires the activation of an eye-specific enhancer of the endogenous hh gene. Keywords: Drosophila; Eye induction; Signaling; Pax6; ey; hh; dpp

The Drosophila HOM-C genes encode transcription factors containing the DNA-binding homeodomain. Mutations in the HOM-C genes can cause specific homeotic transformation, suggesting that the HOM-C genes determine segmental identities by acting on different target genes. However, misexpression of several HOM-C genes in the antenna disc causes similar antenna-to-leg transformations. Here we show that the Scr, Antp, Ubx, and abd-A HOM-C genes all exert their effects through a common mechanism: suppressing the transcription of the homothorax (hth) homeobox gene and thereby preventing the nuclear localization of the Extradenticle homeodomain protein. We also show that ectopic hth expression can cause duplication of the proximodistal axis of the antenna, suggesting that it is involved in proximodistal development of the antenna. Key Words: Drosophila; HOM-C; homeotic transformation; homothorax; antenna; proximodistal axis.

The Drosophila Extradenticle (Exd) protein is a cofactor to homeotic proteins and has regulated nuclear localization. The Drosophila homothorax (hth) gene has been cloned. It is a homolog of the mouse Meis1 proto-oncogene that has a homeobox related to the exd homeobox. The Homothorax homeoprotein suppresses eye development in Drosophila. Hth acts upstream from exd and is required and adequate for Exd protein nuclear localization. It is likely hth works with exd to give parameters to the eye field and to prevent eye development that is not appropriate.

Neurons and glia interact reciprocally. Glia perform many important functions in the development and proper functioning of the nervous system throughout different stages of life. Neurons also affect the development and function of glia. Neurodegenerative diseases are usually late-onset, progressive, and affect specific parts of the nervous system. Many neurodegenerative disorders have been extensively studied. However, the majority of the studies have focused on the events that occur in neurons. The events that occur in glia, and whether and how glia participate in the pathogenesis of these diseases, have not been as well studied. In this review, we will focus on how the fruit flyDrosophila melanogasterhas been used as a model to study neuron–glia interactions in neurodegenerative disorders. We discuss how glia are affected in these models of human neurodegenerative disorders and how glia contribute to their pathogenesis. These studies have provided important insight into the mechanisms of diverse neurodegenerative disorders, and have suggested possibilities for early diagnosis. [ABSTRACT FROM PUBLISHER]

A general question in development is how do adjacent primordia adopt different developmental fates and stably maintain their distinct fates? In Drosophila melanogaster, the adult eye and antenna originate from the embryonic eye-antenna primordium. These cells proliferate in the larval stage to form the eye-antenna disc. The eye or antenna differs at mid second instar with the restricted expression of Cut (Ct), a homeodomain transcriptional repressor, in the antenna disc and Eyeless (Ey), a Pax6 transcriptional activator, in the eye disc. In this study, we show that ey transcription in the antenna disc is repressed by two homeodomain proteins, Ct and Homothorax (Hth). Loss of Ct and Hth in the antenna disc resulted in ectopic eye development in the antenna. Conversely, the Ct and Hth expression in the eye disc was suppressed by the homeodomain transcription factor Sine oculis (So), a direct target of Ey. Loss of So in the eye disc caused ectopic antenna development in the eye. Therefore, the segregation of eye and antenna fates is stably maintained by mutual repression of the other pathway. [ABSTRACT FROM AUTHOR]

Drosophila has two pairs of Pax genes, ey/toy and eyg/toe, that play different functions during eye development. ey specifies eye fate, while eyg promotes cell proliferation. We have determined the molecular basis for the functional diversity of Eyg and Ey. Eyg and Ey act by distinct transcriptional mechanisms. They use different DNA-binding domains for target recognition. Most interestingly, Eyg acts exclusively as a repressor, whereas Ey is an activator. Several vertebrate Pax proteins are known to switch between activator and repressor activities, but none as repressors only. Eyg may be the first Pax protein as a dedicated repressor. Vertebrates produce a Pax6 isoform, Pax6-5a, differing from Pax6 in DNA-binding properties and functions and structurally similar to Eyg/Toe. We found that Pax6-5a acts as an activator like Ey, but has DNA-binding specificity like Eyg. [ABSTRACT FROM AUTHOR]

Notch (N) signal is activated at the dorsoventral (DV) border of the Drosophila eye disc and is important for growth of the eye disc. In this study, we showed that the Pax protein Eyg is a major effector mediating the growth promotion function of N, eyg transcription is induced by N signaling occurring at the DV border. Like N, eyg controls growth of the eye disc. Loss of N signaling can be compensated by overexpressing eyg, whereas loss of the downstream eyg blocked the function of N signaling. In addition, we showed that N and eyg could induce expression of upd, which encodes the ligand for the Jak/STAT pathway and acts over long distance to promote cell proliferation. Loss of eyg or N can be compensated by overexpressing upd. These results suggest that upd is a major effector mediating the function of eyg and N. The functional link from N to eyg to upd explains how the localized Notch activation can achieve global growth control. [ABSTRACT FROM AUTHOR]

Provides information on a study that reported the identification of a Drosophila Pax gene, eye gone, which is required for eye development. Methodology of the study; Results and discussion on the study.

The teashirt (tsh) gene has dorso-ventral (DV) asymmetric functions in Drosophila eye development: promoting eye development in dorsal and suppressing eye development in ventral by Wingless mediated Homothorax (HTH) induction [Development 129 (2002) 4271]. We looked for DV spatial cues required by tsh for its asymmetric functions. The dorsal Iroquois-Complex (Iro-C) genes and Delta (Dl) are required and sufficient for the tsh dorsal functions. The ventral Serrate (Ser), but not fringe (fng) or Lobe (L), is required and sufficient for the tsh ventral function. We propose that DV asymmetric function of tsh represents a novel tier of DV pattern regulation, which takes place after the spatial expression patterns of early DV patterning genes are established in the eye. [Copyright &y& Elsevier]

Notch (N) signal is activated at the dorsoventral (DV) border of the Drosophila eye disc and is important for growth of the eye disc. In this study, we showed that the Pax protein Eyg is a major effector mediating the growth promotion function of N. eyg transcription is induced by N signaling occurring at the DV border. Like N, eyg controls growth of the eye disc. Loss of N signaling can be compensated by overexpressing eyg, whereas loss of the downstream eyg blocked the function of N signaling. In addition, we showed that N and eyg could induce expression of upd, which encodes the ligand for the Jak/STAT pathway and acts over long distance to promote cell proliferation. Loss of eyg or N can be compensated by overexpressing upd. These results suggest that upd is a major effector mediating the function of eyg and N. The functional link from N to eyg to upd explains how the localized Notch activation can achieve global growth control.