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To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ydbio.2005.06.033 Byline: Mary A. Logan, Michael R. Steele, Terence J. Van Raay, Monica L. Vetter Keywords: Proneural; bHLH transcription factor; Neuronal differentiation; Target genes Abstract: Proneural basic helix-loop-helix (bHLH) transcription factors are critical positive regulators of neuronal differentiation in a variety of species and are required for proper differentiation of various subtypes of neurons. Although bHLH factors demonstrate some unique functions during neural development, they share the ability to regulate neuronal differentiation, potentially by targeting overlapping sets of genes. To assess this, we performed a screen in ectoderm animal cap tissue to identify direct transcriptional targets shared by two Xenopus ato-related bHLH factors, Xath5 and XNeuroD. Candidate target genes identified in this screen include several transcriptional regulators (Xebf2, Xebf3, XETOR and NKL), an RNA binding protein (elrC), a cell cycle component (Xgadd45[gamma]) and several novel genes. Overexpression of either Xath5 or XNeuroD induced ectopic in vivo expression of these candidate target genes. Conversely, blocking ato-related bHLH activity prevented endogenous nervous system expression of these genes. Therefore, we have identified a set of genes that can be regulated by multiple ato-related bHLH factors and may function as critical effectors of proneural bHLH-mediated differentiation. Author Affiliation: Department of Neurobiology and Anatomy, University of Utah School of Medicine, Salt Lake City, UT 84132, USA Article History: Received 2 March 2005; Revised 28 June 2005; Accepted 29 June 2005

The ciliary marginal zone is a perpetually self-renewing proliferative neuroepithelium at the perimeter of the retina in amphibians and fish. In the ciliary marginal zone (CMZ), cells are spatially ordered with respect to cellular development, deep stem cells being most peripheral and differentiating retinal progenitors being most central. This spatial gradient in the CMZ recapitulates embryonic retinogenesis and provides a powerful system to examine the relative order of gene expression during this process. A number of neurogenic and proneural genes have been described to have interacting roles in the development of the vertebrate nervous system, and so it is of major importance to put these genes in a hierarchical pathway. In no other system yet described are the developmental stages of neurogenesis arrayed so clearly in a spatial pattern as in the CMZ. We have therefore taken advantage of this system, using double in situ hybridizations on cross sections of the CMZ, to compare the spatial patterns of 15 proneural, neurogenic, and other genes involved in early and late phases of retinal development. In addition, we have positioned these expression patterns with respect to cell division. What emerges from this work is a spatial ordering of gene expression that predicts a genetic hierarchy governing vertebrate retinogenesis. By injecting messenger RNA for some of these genes into blastomeres of the Xenopus embryo and examining the effects on expression of the putative downstream genes, we have been able to corroborate some of the relationships between genes predicted to act sequentially.

Investigations of proto-oncogene product pp60(c-src) revealed that it is targeted to intracellular organelles. Results showed that pp60(c-src) was quantified in synaptic vesicles from the neuroendocrine cell line PC12. A specific association was also observed between c-src protein and the synaptic vesicles that indicated a regulatory role of the c-src protein to synaptic vesicle activity.

Abstract Background Early B cell factor (EBF) family members are transcription factors known to have important roles in several aspects of vertebrate neurogenesis, including commitment, migration and differentiation. Knowledge of how EBF family members contribute to neurogenesis is limited by a lack of detailed understanding of genes that are transcriptionally regulated by these factors. Results We performed a microarray screen in Xenopus animal caps to search for targets of EBF transcriptional activity, and identified candidate targets with multiple roles, including transcription factors of several classes. We determined that, among the most upregulated candidate genes with expected neuronal functions, most require EBF activity for some or all of their expression, and most have overlapping expression with ebf genes. We also found that the candidate target genes that had the most strongly overlapping expression patterns with ebf genes were predicted to be direct transcriptional targets of EBF transcriptional activity. Conclusions The identification of candidate targets that are transcription factor genes, including nscl-1, emx1 and aml1, improves our understanding of how EBF proteins participate in the hierarchy of transcription control during neuronal development, and suggests novel mechanisms by which EBF activity promotes migration and differentiation. Other candidate targets, including pcdh8 and kcnk5, expand our knowledge of the types of terminal differentiated neuronal functions that EBF proteins regulate.

Microglia are engineers of the central nervous system (CNS) both in health and disease. In addition to the canonical immunological roles of clearing damaging entities and limiting the spread of toxicity and death, microglia remodel the CNS throughout life. While they have been extensively studied in disease and injury, due to their highly variable functions, their precise role in these contexts still remains uncertain. Over the past decade, we have greatly expanded our understanding of microglial function, including their essential homeostatic roles during development. Here, we review these developmental roles, identify parallels in disease, and speculate whether developmental mechanisms re‐emerge in disease and injury. Developmental Dynamics 248:98–117, 2019. © 2018 Wiley Periodicals, Inc. Key Findings: Microglia are diverse cells with complex roles in development and disease.Microglia remodel the CNS during development by regulating proliferation, differentiation, neuronal migration, and neuronal integration into circuits.There are transcriptionally distinct subsets of microglia present in development and disease with overlapping gene expression.Developmental microglia have roles that parallel those found in disease.Microglia utilize some of the same molecular pathways in development and disease. [ABSTRACT FROM AUTHOR]

During primary neurogenesis in Xenopus, a cascade of helix-loop-helix (HLH) transcription factors regulates neuronal determination and differentiation. While XNeuroD functions at a late step in this cascade to regulate neuronal differentiation, the factors that carry out terminal differentiation are still unknown. We have isolated a new Xenopus member of the Ebf/Olf-1 family of HLH transcription factors, Xebf3, and provide evidence that, during primary neurogenesis, it regulates neuronal differentiation downstream of XNeuroD. In developing Xenopus embryos, Xebf3 is turned on in the three stripes of primary neurons at stage 15.5, after XNeuroD. In vitro, XEBF3 binds the EBF/OLF-1 binding site and functions as a transcriptional activator. When overexpressed, Xebf3 is able to induce ectopic neurons at neural plate stages and directly convert ectodermal cells into neurons in animal cap explants. Expression of Xebf3 can be activated by XNeuroD both in whole embryos and in animal caps, indicating that this new HLH factor might be regulated by XNeuroD. Furthermore, in animal caps, XNeuroD can activate Xebf3 in the absence of protein synthesis, suggesting that, in vitro, this regulation is direct. Similar to XNeuroD, but unlike Xebf2/Xcoe2, Xebf3 expression and function are insensitive to Delta/Notch-mediated lateral inhibition. In summary, we conclude that Xebf3 functions downstream of XNeuroD and is a regulator of neuronal differentiation in Xenopus. [C] 2001 Academic Press Key Words: Ebf; Olf-1 homolog; HLH transcription factor; primary neurogenesis; Xenopus laevis.

The basic helix-loop-helix (bHLH) factor Xath5 promotes retinal ganglion cell differentiation when overexpressed and may do so by regulating the expression of factors involved in the differentiation of these cells. Potential candidates include the Brn3 POU-homeodomain transcription factors, which have been implicated in retinal ganglion cell development. Here we have identified a new member of the Brn3 gene subfamily in Xenopus, XBrn3d. In situ hybridization analysis shows XBrn3d expression in developing sensory neurons and developing ganglion cells of the retina. Using a hormone-inducible Xath5 fusion protein, we have shown that in animal caps Xath5 can directly regulate the expression of XBrn3d. Since XBrn3d is also expressed in sensory populations where Xath5 is not expressed, we examined the regulation of XBrn3d expression by the bHLH factor XNeuroD. A XNeuroD-hGR fusion protein is similarly able to directly induce the expression of XBrn3d in animal caps. In addition, overexpression of XBrn3d by RNA injection promotes the expression of ectopic sensory neuronal markers in the lateral ectoderm, suggesting a role in regulating neuronal development. Therefore, Xath5 and XNeuroD can directly regulate the expression of a neuronal subtype-specific factor, providing a link between neuronal differentiation and cell fate specification. Key Words: Xenopus; bHLH; Xath5; XNeuroD; XBrn3d; retinogenesis; differentiation.