bluuebunny/crossref_metadata_2025_split huggingface dataset:
The role of the msh homeobox gene during Drosophila neurogenesis: implication for the dorsoventral specification of the neuroectoderm
Authors: Isshiki Takako , Takeichi Masatoshi , Nose Akinao 
Published: April 2021

ABSTRACT
Development of the Drosophila central nervous system begins with the delamination of neural and glial precursors, called neuroblasts, from the neuroectoderm. An early and important step in the generation of neural diversity is the specification of individual neuroblasts according to their position. In this study, we describe the genetic analysis of the msh gene which is likely to play a role in this process. The msh/Msx genes are one of the most highly conserved families of homeobox genes. During vertebrate spinal cord development, Msx genes (Msx1-3) are regionally expressed in the dorsal portion of the developing neuroectoderm. Similarly in Drosophila, msh is expressed in two longitudinal bands that correspond to the dorsal half of the neuroectoderm, and subsequently in many dorsal neuroblasts and their progeny. We showed that Drosophila msh loss-of-function mutations led to cell fate alterations of neuroblasts formed in the dorsal aspect of the neuroectoderm, including a possible dorsal-to-ventral fate switch. Conversely, ectopic expression of msh in the entire neuroectoderm severely disrupted the proper development of the midline and ventral neuroblasts. The results provide the first in vivo evidence for the role of the msh/Msx genes in neural development, and support the notion that they may perform phylogenetically conserved functions in the dorsoventral patterning of the neuroectoderm.
klumpfuss, a Drosophila gene encoding a member of the EGR family of transcription factors, is involved in bristle and leg development
Authors: Klein Thomas , Campos-Ortega José A. 
Published: April 2021

ABSTRACT
The klumpfuss (klu) transcription unit in Drosophila gives rise to two different transcripts of 4.5 and 4.9 kb, both of which encode a putative transcription factor with four zinc-finger motifs of the C2H2 class. Zinc-finger 2-4 are homologous to those of the proteins of the EGR transcription factor family. As in the case of the most divergent member of the family, the Wilms’ tumor suppressor gene (WT-1), klu contains an additional zinc finger, which is only distantly related. Loss of klumpfuss function is semilethal and causes a variety of defects in bristles and legs of adults, as well as in mouth hooks and brains of larvae. Analysis of the mutants indicates that klumpfuss is required for proper specification and differentiation of a variety of cells, including the sensory organ mother cells and those of the distal parts of tarsal segments.
Developmentally regulated activation of apoptosis early in Xenopus gastrulation results in cyclin A degradation during interphase of the cell cycle
Authors: Stack Jeffrey H. , Newport John W. 
Published: April 2021

ABSTRACT
Previous work identified a developmental timer that controls the stability of cyclin A protein in interphase-arrested Xenopus embryos. It was shown that cyclins A1 and A2 abruptly become unstable in hydroxyurea-treated embryos at the time that untreated embryos are beginning gastrulation (early gastrulation transition; EGT). We have demonstrated here that cyclins A1 and A2 are degraded at the equivalent of the EGT by the ICE-like caspases that are responsible for programmed cell death or apoptosis. Analysis of embryos treated with hydroxyurea or cyclo-heximide showed widespread cellular apoptosis coincident with cyclin A cleavage. Our data further indicate that the apoptotic pathway is present in Xenopus embryos prior to the EGT; however, it is maintained in an inactive state in early cleaving embryos by maternally encoded inhibitors. Characterization of the timing of the activation of apoptosis implicates the initiation of zygotic transcription at the mid-blastula transition (MBT) in the suppression of apoptosis in normal embryos. The decreased biosynthetic capacity of embryos treated with hydroxyurea or cycloheximide most likely interferes with the ability to maintain sufficient levels of apoptotic inhibitors and results in widespread apoptosis. Our results suggest a scenario whereby the apoptotic pathway is suppressed in the early cleaving embryo by maternally contributed inhibitors. Degradation at the EGT of maternal RNAs encoding these inhibitors is compensated for by new zygotic transcription beginning at the MBT. This indicates that the interval between the MBT and the EGT represents a critical developmental period during which the regulation of embryonic cellular processes is transferred from maternal to zygotic control.
Role of GGF/neuregulin signaling in interactions between migrating neurons and radial glia in the developing cerebral cortex
Authors: Anton E. S. , Marchionni M. A. , Lee K-F. , Rakic P. 
Published: April 2021

ABSTRACT
During neuronal migration to the developing cerebral cortex, neurons regulate radial glial cell function and radial glial cells, in turn, support neuronal cell migration and differentiation. To study how migrating neurons and radial glial cells influence each others’ function in the developing cerebral cortex, we examined the role of glial growth factor (a soluble form of neuregulin), in neuron-radial glial interactions. Here, we show that GGF is expressed by migrating cortical neurons and promotes their migration along radial glial fibers. Concurrently, GGF also promotes the maintenance and elongation of radial glial cells, which are essential for guiding neuronal migration to the cortex. In the absence of GGF signaling via erbB2 receptors, radial glial development is abnormal. Furthermore, GGF’s regulation of radial glial development is mediated in part by brain lipid-binding protein (BLBP), a neuronally induced, radial glial molecule, previously shown to be essential for the establishment and maintenance of radial glial fiber system. The ability of GGF to influence both neuronal migration and radial glial development in a mutually dependent manner suggests that it functions as a mediator of interactions between migrating neurons and radial glial cells in the developing cerebral cortex.
Cell migration in the developing chick diencephalon
Authors: Golden Jeffrey A. , Zitz Julie C. , McFadden Kathryn , Cepko Constance L. 
Published: April 2021

ABSTRACT
We previously reported that retrovirally marked clones in the mature chick diencephalon were widely dispersed in the mediolateral, dorsoventral and rostrocaudal planes. The current study was undertaken to define the migration routes that led to the dispersion. Embryos were infected between stages 10 and 14 with a retroviral stock encoding alkaline phosphatase and a library of molecular tags. Embryos were harvested 2.5-5.5 days later and the brains were fixed and serially sectioned. Sibling relationships were determined following PCR amplification and sequencing of the molecular tag. On embryonic day 4, all clones were organized in radial columns spanning the neuroepithelium, which was composed primarily of a ventricular zone at this age. No tangential migration was seen in the ventricular zone. On embryonic day 5, most clones remained radial with many cells located in the ventricular zone; however, a few clones had cells migrating perpendicular to the radial column, in either a rostrocaudal or dorsoventral direction. The tangential migration began just beyond the basal limit of the ventricular zone. On embryonic days 6 and 7, many clones had cells migrating perpendicular to the radial column, which spanned from the ventricular to the pial surface. The migrating cells appeared to be aligned along axes that were perpendicular to the radial column. Using a combination of DiI tracing, immunohistochemistry and electron microscopy, we have determined that axonal tracts are present and are aligned with the migrating cells, suggesting that they support the non-radial cell migration. These data indicate that migration along pathways independent of radial glia occur outside of the ventricular zone in more than 50% of the clones in the chick diencephalon.
Targeted disruption of the mouse homologue of the Drosophila polyhomeotic gene leads to altered anteroposterior patterning and neural crest defects
Authors: Takihara Yoshihiro , Tomotsune Daihachiro , Shirai Manabu , Katoh-Fukui Yuko , Nishii Kiyomasa , Motaleb Md. Abdul , Nomura Midori , Tsuchiya Reiko , Fujita Yoshiaki , Shibata Yosaburo , Higashinakagawa Toru , Shimada Kazunori 
Published: April 2021

ABSTRACT
The rae28 gene is a mouse homologue of the Drosophila polyhomeotic gene (Nomura, M., Takihara, Y. and Shimada, K. (1994) Differentiation 57, 39-50), which is a member of the Polycomb group (Pc-G) of genes (DeCamillis, M., Cheng, N., Pierre, D. and Brock, H.W. (1992) Genes Dev. 6, 223-232). The Pc-G genes are required for the correct expression of the Homeotic complex genes and segment specification during Drosophila embryogenesis and larval development. To study the role of the rae28 gene in mouse development, we generated rae28-deficient mice by gene targeting in embryonic stem cells. The rae28−/− homozygous mice exhibited perinatal lethality, posterior skeletal transformations and defects in neural crest-related tissues, including ocular abnormalities, cleft palate, parathyroid and thymic hypoplasia and cardiac anomalies.
The anterior boundaries of Hoxa-3, a-4, a-5, b-3, b-4 and d-4 expression were shifted rostrally in the paraxial mesoderm of the rae28−/− homozygous embryos, and those of Hoxb-3 and b-4 expression were also similarly altered in the rhombomeres and/or pharyngeal arches. These altered Hox codes were presumed to be correlated with the posterior skeletal transformations and neural crest defects observed in the rae28−/− homozygous mice. These results indicate that the rae28 gene is involved in the regulation of Hox gene expression and segment specification during paraxial mesoderm and neural crest development.
Role of Hoxa-2 in axon pathfinding and rostral hindbrain patterning
Authors: Gavalas Anthony , Davenne Marc , Lumsden Andrew , Chambon Pierre , Rijli Filippo M. 
Published: April 2021

ABSTRACT
Segmentation plays an important role in neuronal diversification and organisation in the developing hindbrain. For instance, cranial nerve branchiomotor nuclei are organised segmentally within the basal plates of successive pairs of rhombomeres. To reach their targets, motor axons follow highly stereotyped pathways exiting the hindbrain only via specific exit points in the even-numbered rhombomeres. Hox genes are good candidates for controlling this pathfinding, since they are segmentally expressed and involved in rhom-bomeric patterning. Here we report that in Hoxa-2−/− embryos, the segmental identities of rhombomere (r) 2 and r3 are molecularly as well as anatomically altered. Cellular analysis by retrograde dye labelling reveals that r2 and r3 trigeminal motor axons turn caudally and exit the hindbrain from the r4 facial nerve exit point and not from their normal exit point in r2. Furthermore, dorsal r2-r3 patterning is affected, with loss of cochlear nuclei and enlargement of the lateral part of the cerebellum. These results point to a novel role for Hoxa-2 in the control of r2-r3 motor axon guidance, and also suggest that its absence may lead to homeotic changes in the alar plates of these rhombomeres.
The roles of hedgehog and engrailed in patterning adult abdominal segments of Drosophila
Authors: Kopp Artyom , Muskavitch Marc A. T. , Duncan Ian 
Published: April 2021

ABSTRACT
We present evidence that hedgehog (hh) protein secreted by posterior compartment cells plays a key role in patterning the posterior portion of the anterior compartment in adult abdominal segments. Loss of function of hh in the hhts2 mutant causes the loss of posterior tergite characteristics in the anterior compartment, whereas ectopic expression driven by hs-hh or the gain-of-function allele hhMir causes transformation of anterior structures toward the posterior. FLP-out hh-expressing clones in the anterior compartment induce surrounding wild-type cells to produce posterior tergite structures, establishing that hh functions non-autonomously. The effects of pulses of ectopic expression driven by hs-hh indicate that bristle type and pigmentation are patterned by hh at widely different times in pupal development.
We also present evidence that the primary polarization of abdominal segments is symmetric. This symmetry is strikingly revealed by ectopic expression of engrailed (en). As expected, this transforms anterior compartment cells to posterior compartment identity. In addition, however, ectopic en expression causes an autonomous reversal of polarity in the anterior portion of the anterior compart-ment, but not the posterior portion. By determining the position of polarity reversal within en-expressing clones, we were able to define a cryptic line of symmetry that lies within the pigment band of the normal tergite. This line appears to be retained in hhts2 mutants raised at the restrictive temperature, suggesting it is not established by hh signaling. We argue that the primary role of hh in control-ling polarity is to cause anterior compartment cells to reverse their interpretation of an underlying symmetric polarization. Consistent with this, we find that strong ectopic expression of hh causes mirror-symmetric double posterior patterning, whereas hh loss of function can cause mirror-symmetric double anterior patterning.
The maternal par genes and the segregation of cell fate specification activities in early Caenorhabditis elegans embryos
Authors: Bowerman Bruce , Ingram Malene K. , Hunter Craig P. 
Published: April 2021

ABSTRACT
After fertilization in C. elegans, activities encoded by the maternally expressed par genes appear to establish cellular and embryonic polarity. Loss-of-function mutations in the par genes disrupt anterior-posterior (a-p) asymmetries in early embryos and result in highly abnormal patterns of cell fate. Little is known about how the early asymmetry defects are related to the cell fate patterning defects in par mutant embryos, or about how the par gene products affect the localization and activities of developmental regulators known to specify the cell fate patterns made by individual blastomeres. Examples of such regulators of blastomere identity include the maternal proteins MEX-3 and GLP-1, expressed at high levels anteriorly, and SKN-1 and PAL-1, expressed at high levels posteriorly in early embryos. To better define par gene functions, we examined the expression patterns of MEX-3, PAL-1 and SKN-1, and we analyzed mex-3, pal-1, skn-1 and glp-1 activities in par mutant embryos. We have found that mutational inactivation of each par gene results in a unique phenotype, but in no case do we observe a complete loss of a-p asymmetry. We conclude that no one par gene is required for all a-p asymmetry and we suggest that, in some cases, the par genes act independently of each other to control cell fate patterning and polarity. Finally, we discuss the implications of our findings for understanding how the initial establishment of polarity in the zygote by the par gene products leads to the proper localization of more specifically acting regulators of blastomere identity.
Notch signalling mediates segmentation of the Drosophila leg
Authors: de Celis Jose F. , Tyler David M. , Celis Jesus de , Bray Sarah J. 
Published: April 2021

SUMMARY
The legs of Drosophila are divided into segments along the proximodistal axis by flexible structures called joints. The separation between segments is already visible in the imaginal disc as folds of the epithelium, and cells at segment boundaries have different morphology during pupal development. We find that Notch is locally activated in distal cells of each segment, as demonstrated by the restricted expression of the Enhancer of split mβ gene, and is required for the formation of normal joints. The genes fringe, Delta, Serrate and Suppressor of Hairless, also participate in Notch function during leg development, and their expression is localised within the leg segments with respect to segment boundaries. The failure to form joints when Notch signalling is compromised leads to shortened legs, suggesting that the correct specification of segment boundaries is critical for normal leg growth. The requirement for Notch during leg development resembles that seen during somite formation in vertebrates and at the dorsal ventral boundary of the wing, suggesting that the creation of boundaries of gene expression through Notch activation plays a conserved role in co-ordinating growth and patterning.
Repression of hedgehog signaling and BMP4 expression in growth plate cartilage by fibroblast growth factor receptor 3
Authors: Naski Michael C. , Colvin Jennifer S. , Coffin J. Douglas , Ornitz David M. 
Published: April 2021

ABSTRACT
Fibroblast growth factor receptor 3 (FGFR3) is a key regulator of skeletal growth and activating mutations in Fgfr3 cause achondroplasia, the most common genetic form of dwarfism in humans. Little is known about the mechanism by which FGFR3 inhibits bone growth and how FGFR3 signaling interacts with other signaling pathways that regulate endochondral ossification. To understand these mechanisms, we targeted the expression of an activated FGFR3 to growth plate cartilage in mice using regulatory elements from the collagen II gene. As with humans carrying the achondroplasia mutation, the resulting transgenic mice are dwarfed, with axial, appendicular and craniofacial skeletal hypoplasia. We found that FGFR3 inhibited endochondral bone growth by markedly inhibiting chondrocyte proliferation and by slowing chondrocyte differentiation. Significantly, FGFR3 downregulated the Indian hedgehog (Ihh) signaling pathway and Bmp4 expression in both growth plate chondrocytes and in the perichondrium. Conversely, Bmp4 expression is upregulated in the perichondrium of Fgfr3−/− mice. These data support a model in which Fgfr3 is an upstream negative regulator of the hedgehog (Hh) signaling pathway. Additionally, Fgfr3 may coordinate the growth and differentiation of chondrocytes with the growth and differentiation of osteoprogenitor cells by simultaneously modulating Bmp4 and patched expression in both growth plate cartilage and in the perichondrium.
zfh-1 is required for germ cell migration and gonadal mesoderm development in Drosophila
Authors: Broihier Heather Tarczy , Moore Lisa A. , Doren Mark Van , Newman Stephanie , Lehmann Ruth 
Published: April 2021

ABSTRACT
In Drosophila as well as many vertebrate systems, germ cells form extraembryonically and migrate into the embryo before navigating toward gonadal mesodermal cells. How the gonadal mesoderm attracts migratory germ cells is not understood in any system. We have taken a genetic approach to identify genes required for germ cell migration in Drosophila. Here we describe the role of zfh-1 in germ cell migration to the gonadal mesoderm. In zfh-1 mutant embryos, the initial association of germ cells and gonadal mesoderm is blocked. Loss of zfh-1 activity disrupts the development of two distinct mesodermal populations: the caudal visceral mesoderm and the gonadal mesoderm. We demonstrate that the caudal visceral mesoderm facilitates the migration of germ cells from the endoderm to the mesoderm. Zfh-1 is also expressed in the gonadal mesoderm throughout the development of this tissue. Ectopic expression of Zfh-1 is sufficient to induce additional gonadal mesodermal cells and to alter the temporal course of gene expression within these cells. Finally, through analysis of a tinman zfh-1 double mutant, we show that zfh-1 acts in conjunction with tinman, another homeodomain protein, in the specification of lateral mesodermal derivatives, including the gonadal mesoderm.
Nanos and Pumilio have critical roles in the development and function of Drosophila germline stem cells
Authors: Forbes Alexandria , Lehmann Ruth 
Published: April 2021

ABSTRACT
The zinc-finger protein Nanos and the RNA-binding protein Pumilio act together to repress the translation of maternal hunchback RNA in the posterior of the Drosophila embryo, thereby allowing abdomen formation. nanos RNA is localized to the posterior pole during oogenesis and the posteriorly synthesized Nanos protein is sequestered into the germ cells as they form in the embryo. This maternally provided Nanos protein is present in germ cells throughout embryogenesis. Here we show that maternally deposited Nanos protein is essential for germ cell migration. Lack of zygotic activity of nanos and pumilio has a dramatic effect on germline development of homozygous females. Given the coordinate function of nanos and pumilio in embryonic patterning, we analyzed the role of these genes in oogenesis. We find that both genes act in the germline. Although the nanos and pumilio ovarian phenotypes have similarities and both genes ultimately affect germline stem cell development, the focus of these phenotypes appears to be different. While pumilio mutant ovaries fail to maintain stem cells and all germline cells differentiate into egg chambers, the focus of nanos function seems to lie in the differentiation of the stem cell progeny, the cystoblast. Consistent with the model that nanos and pumilio have different phenotypic foci during oogenesis, we detect high levels of Pumilio protein in the germline stem cells and high levels of Nanos in the dividing cystoblasts. We therefore suggest that, in contrast to embryonic patterning, Nanos and Pumilio may interact with different partners in the germline.
Requirements for the cytoplasmic domain of the αPS1, αPS2 and βPS integrin subunits during Drosophila development
Authors: Li Xitong , Graner Michael W. , Williams Erin L. , Roote Carol E. , Bunch Thomas A. , Zusman Susan 
Published: April 2021

ABSTRACT
The integrins are a family of transmembrane heterodimeric proteins that mediate adhesive interactions and participate in signaling across the plasma membrane. In this study we examine the functional significance of the cytoplasmic domains of the αPS1, αPS2 and βPS subunits of the Drosophila Position Specific (PS) integrin family by analyzing the relationship between cytoplasmic domain structure and function in the context of a developing organism. By examining the ability of βPS molecules lacking the cytoplasmic domain to rescue embryonic abnormalities associated with PS integrin loss, we find that although many embryonic events require the βPS cytoplasmic domain, this portion of the molecule is not required for at least two processes requiring PS integrins: formation of midgut constrictions and maintaining germband integrity. Furthermore, our studies demonstrate that mutant proteins affecting four highly conserved amino acid residues in the cytoplasmic tail function with different efficiencies during embryonic development, suggesting that interaction of PS integrins with cytoplasmic ligands is developmentally modulated during embryogenesis.
We have also examined the ability of αPS1 and αPS2 to function without their cytoplasmic domains. By analyzing the ability of transgenes producing truncated αPS molecules to rescue abnormalities associated with integrin loss, we find that the cytoplasmic tail of αPS2 is essential for both embryonic and postembryonic processes, while this portion of αPS1 is not required for function in the wing and in the retina. Furthermore, temperature-shift experiments suggest roles for the αPS2 cytoplasmic domain in signaling events occurring in the developing wing.