http://www.biomedcentral.com/bmcdevbiol/ The latest research articles published by BMC Developmental Biology 2009-12-03T00:00:00Z This is an RSS newsfeed from BioMed Central It is intended to be used with an RSS reader. For more information about RSS newsfeeds from BioMed Central, visit http://www.biomedcentral.com/info/about/rss/ Background: During early steps of embryonic development the hindbrain undergoes a regionalization process along the anterior-posterior (AP) axis that leads to a metameric organization in a series of rhombomeres (r). Refinement of the AP identities within the hindbrain requires the establishment of local signaling centers, which emit signals that pattern territories in their vicinity. Previous results demonstrated that the transcription factor vHnf1 confers caudal identity to the hindbrain inducing Krox20 in r5 and MafB/Kreisler in r5 and r6, through FGF signaling [1]. Results: We show that in the chick hindbrain, Fgf3 is transcriptionally activated as early as 30min after mvHnf1 electroporation, suggesting that it is a direct target of this transcription factor. We also analyzed the expression profiles of FGF activity readouts, such as MKP3 and Pea3, and showed that both are expressed within the hindbrain at early stages of embryonic development. In addition, MKP3 is induced upon overexpression of mFgf3 or mvHnf1 in the hindbrain, confirming vHnf1 is upstream FGF signaling. Finally, we addressed the question of which of the FGF-responding intracellular pathways were active and involved in the regulation of Krox20 and MafB in the hindbrain. While Ras-ERK1/2 activity is necessary for MKP3, Krox20 and MafB induction, PI3K-Akt is not involved in that process. Conclusion: Based on these observations we propose that vHnf1 acts directly through FGF3, and promotes caudal hindbrain identity by activating MafB and Krox20 via the Ras-ERK1/2 intracellular pathway. http://www.biomedcentral.com/1471-213X/9/61 Ferran Aragon Cristina Pujades BMC Developmental Biology 2009, 9:61 2009-12-03T00:00:00Z doi:10.1186/1471-213X-9-61 BMC Developmental Biology 1471-213X 9 61 2009-12-03T00:00:00Z PDF Background: Proper patterning of the follicle cell epithelium over the egg chamber is essential for the Drosophila egg development. Differentiation of the epithelium into several distinct cell types along the anterior-posterior axis requires coordinated activities of multiple signaling pathways. Previously, we reported that lethal(2)giant larvae (lgl), a Drosophila tumor suppressor gene, is required in the follicle cells for the posterior follicle cell (PFC) fate induction at mid-oogenesis. Here we explore the role of another two tumor suppressor genes, scribble (scrib) and discs large (dlg), in the epithelial patterning. Results: We found that removal of scrib or dlg function from the follicle cells at posterior terminal of the egg chamber causes a complete loss of the PFC fate. Aberrant specification and differentiation of the PFCs in the mosaic clones can be ascribed to defects in coordinated activation of the EGFR, JAK and Notch signaling pathways in the multilayered cells. Meanwhile, the clonal analysis revealed that loss-of-function mutations in scrib/dlg at the anterior domains result in a partially penetrant phenotype of defective induction of the stretched and centripetal cell fate, whereas specification of the border cell fate can still occur in the most anterior region of the mutant clones. Further, we showed that scrib genetically interacts with dlg in regulating posterior patterning of the epithelium. Conclusions: In this study we provide evidence that scrib and dlg function differentially in anterior and posterior patterning of the follicular epithelium at oogenesis. Further genetic analysis indicates that scrib and dlg act in a common pathway to regulate PFC fate induction. This study may open another window for elucidating role of scrib/dlg in controlling epithelial polarity and cell proliferation during development. http://www.biomedcentral.com/1471-213X/9/60 Qi Li Ling Shen Tianchi Xin Wenjuan Xiang Wenlian Chen Yin Gao Mingwei Zhu Lingzhu Yu Mingfa Li BMC Developmental Biology 2009, 9:60 2009-12-01T00:00:00Z doi:10.1186/1471-213X-9-60 BMC Developmental Biology 1471-213X 9 60 2009-12-01T00:00:00Z PDF Background: The vertebrate head skeleton is derived largely from cranial neural crest cells (CNCC). Genetic studies in zebrafish and mice have established that the Hedgehog (Hh)-signaling pathway plays a critical role in craniofacial development, partly due to the pathway's role in CNCC development. Disruption of the Hh-signaling pathway in humans can lead to the spectral disorder of Holoprosencephaly (HPE), which is often characterized by a variety of craniofacial defects including midline facial clefting and cyclopia [1,2]. Previous work has uncovered a role for Hh-signaling in zebrafish dorsal neurocranium patterning and chondrogenesis, however Hh-signaling mutants have not been described with respect to the ventral pharyngeal arch (PA) skeleton. Lipid-modified Hh-ligands require the transmembrane-spanning receptor Dispatched 1 (Disp1) for proper secretion from Hh-synthesizing cells to the extracellular field where they act on target cells. Here we study chameleon mutants, lacking a functional disp1(con/disp1). Results: con/disp1 mutants display reduced and dysmorphic mandibular and hyoid arch cartilages and lack all ceratobranchial cartilage elements. CNCC specification and migration into the PA primordia occurs normally in con/disp1 mutants, however disp1 is necessary for post-migratory CNCC patterning and differentiation. We show that disp1 is required for post-migratory CNCC to become properly patterned within the first arch, while the gene is dispensable for CNCC condensation and patterning in more posterior arches. Upon residing in well-formed pharyngeal epithelium, neural crest condensations in the posterior PA fail to maintain expression of two transcription factors essential for chondrogenesis, sox9a and dlx2a, yet continue to robustly express other neural crest markers. Histology reveals that posterior arch residing-CNCC differentiate into fibrous-connective tissue, rather than becoming chondrocytes. Treatments with Cyclopamine, to inhibit Hh-signaling at different developmental stages, reveal that Hh-signaling is required during gastrulation for proper mandibular arch development, and then during the late pharyngula stage, to promote CNCC chondrogenesis within the posterior arches. Further, loss of disp1 disrupted normal expression of bapx1 and gdf5, markers of jaw joint patterning, thus resulting in jaw joint defects in con/disp1 mutant animals. Conclusion: This study reveals novel requirements for Hh-signaling in the zebrafish PA skeleton and highlights the functional diversity and differential sensitivity of craniofacial tissues to Hh-signaling throughout the face, a finding that may help to explain the spectrum of human facial phenotypes characteristic of HPE. http://www.biomedcentral.com/1471-213X/9/59 Tyler Schwend Sara Ahlgren BMC Developmental Biology 2009, 9:59 2009-11-30T00:00:00Z doi:10.1186/1471-213X-9-59 BMC Developmental Biology 1471-213X 9 59 2009-11-30T00:00:00Z PDF Background: The lateral line system in zebrafish is composed of a series of organs called neuromasts, which are distributed over the body surface. Neuromasts contain clusters of hair cells, surrounded by accessory cells. Results: In this report we describe zebrafish prox1 mRNA expression in the migrating primordium and in the neuromasts of the posterior lateral line. Furthermore, using an antibody against Prox1 we characterize expression of the protein in different cell types within neuromasts, and we show distribution among the supporting cells and hair cells. Conclusion: Functional analysis using antisense morpholinos indicates that prox1 activity is crucial for the hair cells to differentiate properly and acquire functionality, while having no role in development of other cell types in neuromasts. http://www.biomedcentral.com/1471-213X/9/58 Anna Pistocchi Carmen Feijoo Pablo Cabrera Eduardo Villablanca Miguel Allende Franco Cotelli BMC Developmental Biology 2009, 9:58 2009-11-30T00:00:00Z doi:10.1186/1471-213X-9-58 BMC Developmental Biology 1471-213X 9 58 2009-11-30T00:00:00Z PDF Background: Nervous system development is dependent on early regional differentiation to create functionally distinct tissues within an initially undifferentiated zone. Within the retina, photoreceptors are topographically organized with rod free area centrales are faithfully generated at the centre of gaze. How does the developing eye regulate this placement? Conventional wisdom indicates that the distal tip of the growing optic vesicle (OV) gives rise to the area centralis/fovea. Ectopic expression and ablation studies do not fully support this view, creating a controversy as to the origin of this region. In this study, the lineage of cells in the chicken OV was traced using DiI. The location of labelled cells was mapped onto the retina in relation to the rod-free zone at E7 and E17.5. The ability to regenerate a rod free area after OV ablation was determined in conjunction with lineage tracing. Results: Anterior OV gave rise to cells in nasal retina and posterior OV became temporal retina. The OV distal tip gave rise to cells above the optic nerve head. A dorsal and anterior region of the OV correlated with cells in the developing rod free area centralis. Only ablations including the dorsal anterior region gave rise to a retina lacking a rod free zone. DiI application after ablation indicated that cells movements were greater along the anterior posterior axis compared with the dorsal ventral axis. Conclusions: Our data support the idea that the chicken rod free area centralis originates from cells located near, but not at the distal tip of the developing OV. Therefore, the hypothesis that the area centralis is derived from cells at the distal tip of the OV is not supported; rather, a region anterior and dorsal to the distal tip gives rise to the rod free region. When compared with other studies of retinal development, our results are supported on molecular, morphological and functional levels. Our data will lead to a better understanding of the mechanisms underlying the topographic organization of the retina, the origin of the rod free zone, and the general issue of compartmentalization of neural tissue before any indication of morphological differentiation. http://www.biomedcentral.com/1471-213X/9/57 Sae Kyung Shin Keely Bumsted O'Brien BMC Developmental Biology 2009, 9:57 2009-11-25T00:00:00Z doi:10.1186/1471-213X-9-57 BMC Developmental Biology 1471-213X 9 57 2009-11-25T00:00:00Z PDF Background: The Drosophila CNS midline cells are an excellent model system to study neuronal and glial development because of their diversity of cell types and the relative ease in identifying and studying the function of midline-expressed genes. In situ hybridization experiments generated a large dataset of midline gene expression patterns. To help synthesize these data and make them available to the scientific community, we developed a web-accessible database.DescriptionMidExDB (Drosophila CNS Midline Gene Expression Database) is comprised of images and data from our in situ hybridization experiments that examined midline gene expression. Multiple search tools are available to allow each type of data to be viewed and compared. Descriptions of each midline cell type and their development are included as background information. Conclusion: MidExDB integrates large-scale gene expression data with the ability to identify individual cell types providing the foundation for detailed genetic, molecular, and biochemical studies of CNS midline cell neuronal and glial development and function. This information has general relevance for the study of nervous system development in other organisms, and also provides insight into transcriptional regulation. http://www.biomedcentral.com/1471-213X/9/56 Scott Wheeler Stephanie Stagg Stephen Crews BMC Developmental Biology 2009, 9:56 2009-11-10T00:00:00Z doi:10.1186/1471-213X-9-56 BMC Developmental Biology 1471-213X 9 56 2009-11-10T00:00:00Z XML Background: Brisken et al (2000) showed that Wnt4 null mammary glands were deficient in early lobuloalveolar mammary outgrowth during pregnancy, and implicated Wnt4 as an effector for the progesterone-induced mammary growth program. Though ectopic Wnt1 signaling is known to be mitogenic and oncogenic, no endogenously expressed Wnt ligands have ever been directly implicated in mammary growth and morphogenesis. Therefore, we generated conditional transgenic mice to test whether Wnt4 can stimulate mammary epithelial cell growth. Results: We found that despite pregnancy-associated expression levels of Wnt4, mammary glands did not display the side-branching typical of early pregnancy. Control experiments designed to test the Wnt4 construct in zebrafish reproduced other studies that demonstrated Wnt4-specific phenotypes distinct from Wnt1-induced phenotypes. Indeed, using qPCR-based array analyses, we found that a specific transcriptional target of Wnt4, namely Wnt16, was induced in Wnt4-expressing transgenic glands, to levels equivalent to that of early pregnant glands. Conclusion: Taken together, we propose that Wnt4 is necessary, but not sufficient, to induce side-branch development. http://www.biomedcentral.com/1471-213X/9/55 Young Chul Kim Rod Clark Francisco Pelegri Caroline Alexander BMC Developmental Biology 2009, 9:55 2009-10-30T00:00:00Z doi:10.1186/1471-213X-9-55 BMC Developmental Biology 1471-213X 9 55 2009-10-30T00:00:00Z XML Background: Smad4 mutant embryos arrest shortly after implantation and display a characteristic shortened proximodistal axis, a significantly reduced epiblast, as well as a thickened visceral endoderm layer. Conditional rescue experiments demonstrate that bypassing the primary requirement for Smad4 in the extra-embryonic endoderm allows the epiblast to gastrulate. Smad4-independent TGF-β signals are thus sufficient to promote mesoderm formation and patterning. To further analyse essential Smad4 activities contributed by the extra-embryonic tissues, and characterise Smad4 dependent pathways in the early embryo, here we performed transcriptional profiling of Smad4 null embryonic stem (ES) cells and day 4 embryoid bodies (EBs). Results: Transcripts from wild-type versus Smad4 null ES cells and day 4 EBs were analysed using Illumina arrays. In addition to several known TGF-β/BMP target genes, we identified numerous Smad4-dependent transcripts that are mis-expressed in the mutants. As expected, mesodermal cell markers were dramatically down-regulated. We also observed an increase in non-canonical potency markers (Pramel7, Tbx3, Zscan4), germ cell markers (Aire, Tuba3a, Dnmt3l) as well as early endoderm markers (Dpp4, H19, Dcn). Additionally, expression of the extracellular matrix (ECM) remodelling enzymes Mmp14 and Mmp9 was decreased in Smad4 mutant ES and EB populations. These changes, in combination with increased levels of laminin alpha1, cause excessive basement membrane deposition. Similarly, in the context of the Smad4 null E6.5 embryos we observed an expanded basement membrane (BM) associated with the thickened endoderm layer. Conclusion: Smad4 functional loss results in a dramatic shift in gene expression patterns and in the endodermal cell lineage causes an excess deposition of, or an inability to breakdown and remodel, the underlying BM layer. These structural abnormalities probably disrupt reciprocal signalling between the epiblast and overlying visceral endoderm required for gastrulation. http://www.biomedcentral.com/1471-213X/9/54 Ita Costello Christine Biondi Jennifer Taylor Elizabeth Bikoff Elizabeth Robertson BMC Developmental Biology 2009, 9:54 2009-10-22T00:00:00Z doi:10.1186/1471-213X-9-54 BMC Developmental Biology 1471-213X 9 54 2009-10-22T00:00:00Z XML Background: Programmed cell death, or apoptosis, is a fundamental physiological process during normal development or in pathological conditions. The activation of apoptosis can be elicited by numerous signalling pathways. Ras is known to mediate anti-apoptotic signals by inhibiting Hid activity in the Drosophila eye. Here we report the isolation of a new loss-of-function ras allele, rasKP, which causes excessive apoptosis in the Drosophila eye. Results: This new function is likely to be mediated through the JNK pathway since the inhibition of JNK signalling can significantly suppress rasKP-induced apoptosis, whereas the removal of hid only weakly suppresses the phenotype. Furthermore, the reduction of JNK signalling together with the expression of the baculovirus caspase inhibitor p35, which blocks Hid activity, strongly suppresses the rasKP cell death. In addition, we find a strong correlation between rasKP-induced apoptosis in the eye disc and the activation of JNK signalling. Conclusion: In the Drosophila eye, Ras may protect cells from apoptosis by inhibiting both JNK and Hid activities. Surprisingly, reducing Ras activity in the wing, however, does not cause apoptosis but rather affects cell and organ size. Thus, in addition to its requirement for cell viability, Ras appears to mediate different biological roles depending on the developmental context and on the level of its expression. http://www.biomedcentral.com/1471-213X/9/53 Yue Wu Yuan Zhuang Min Han Tian Xu Kejing Deng BMC Developmental Biology 2009, 9:53 2009-10-20T00:00:00Z doi:10.1186/1471-213X-9-53 BMC Developmental Biology 1471-213X 9 53 2009-10-20T00:00:00Z XML Background: The roles of the Hedgehog (Hh) pathway in controlling vertebrate retinal development have been studied extensively; however, species- and context-dependent findings have provided differing conclusions. Hh signaling has been shown to control both population size and cell cycle kinetics of proliferating retinal progenitors, and to modulate differentiation within the retina by regulating the timing of cell cycle exit. While cell cycle exit has in turn been shown to control cell fate decisions within the retina, a direct role for the Hh pathway in retinal cell fate decisions has yet to be established in vivo. Results: To gain further insight into Hh pathway function in the retina, we have analyzed retinal development in leprechaun/patched2 mutant zebrafish. While lep/ptc2 mutants possessed more cells in their retinas, all cell types, except for Müller glia, were present at identical ratios as those observed in wild-type siblings. lep/ptc2 mutants possessed a localized upregulation of GFAP, a marker for 'reactive' glia, as well as morphological abnormalities at the vitreo-retinal interface, where Müller glial endfeet terminate. In addition, analysis of the over-proliferation phenotype at the ciliary marginal zone (CMZ) revealed that the number of proliferating progenitors, but not the rate of proliferation, was increased in lep/ptc2 mutants. Conclusion: Our results indicate that Patched2-dependent Hh signaling does not likely play an integral role in neuronal cell fate decisions in the zebrafish retina. ptc2 deficiency in zebrafish results in defects at the vitreo-retinal interface and Müller glial reactivity. These phenotypes are similar to the ocular abnormalities observed in human patients suffering from Basal Cell Naevus Syndrome (BCNS), a disorder that has been linked to mutations in the human PTCH gene (the orthologue of the zebrafish ptc2), and point to the utility of the lep/ptc2 mutant line as a model for the study of BCNS-related ocular pathologies. Our findings regarding CMZ progenitor proliferation suggest that, in the zebrafish retina, Hh pathway activity may not affect cell cycle kinetics; rather, it likely regulates the size of the retinal progenitor pool in the CMZ. http://www.biomedcentral.com/1471-213X/9/52 Jonathan Bibliowicz Jeffrey Gross BMC Developmental Biology 2009, 9:52 2009-10-19T00:00:00Z doi:10.1186/1471-213X-9-52 BMC Developmental Biology 1471-213X 9 52 2009-10-19T00:00:00Z XML