A new Drosophila homeobox gene, bsh, is expressed in a subset of brain cells during embryogenesis

Homeobox genes have been shown to control the determination of positional, tissue and cellular identity during the development of the fruitfly Drosophila melanogaster. Because genes involved in the determination of internal structures derived from neural, mesodermal and endodermal tissues may have been overlooked in conventional genetic screens, we undertook the identification of new homeobox genes expressed in these internal tissues. Here we describe the characterization of one of these new Drosophila homeobox genes, called brain-specific-homeobox (bsh). In embryos, bsh is expressed exclusively in the brain. bsh protein accumulates in approximately 30 cells in each brain hemisphere. One of these bsh expressing cells is closely associated with the terminus of the larval visual nerve (Bolwig's nerve). While deletions of chromosomal interval containing the bsh gene show no dramatic changes in embryonic brain morphology, the expression pattern of the bsh gene suggests that it may play a highly specialized role in the determination and function of cell type in the Drosophila brain.

Download Full-text

The Caenorhabditis elegans lim-6 LIM homeobox gene regulates neurite outgrowth and function of particular GABAergic neurons

Development ◽

10.1242/dev.126.7.1547 ◽

1999 ◽

Vol 126 (7) ◽

pp. 1547-1562 ◽

Cited By ~ 9

Author(s):

O. Hobert ◽

K. Tessmar ◽

G. Ruvkun

Keyword(s):

Epithelial Cells ◽

Homeobox Genes ◽

Homeobox Gene ◽

Acid Decarboxylase ◽

Neural Function ◽

C Elegans ◽

Gaba Synthesis ◽

And Function ◽

Rate Limiting ◽

Enteric Muscle

We describe here the functional analysis of the C. elegans LIM homeobox gene lim-6, the ortholog of the mammalian Lmx-1a and b genes that regulate limb, CNS, kidney and eye development. lim-6 is expressed in a small number of sensory-, inter- and motorneurons, in epithelial cells of the uterus and in the excretory system. Loss of lim-6 function affects late events in the differentiation of two classes of GABAergic motorneurons which control rhythmic enteric muscle contraction. lim-6 is required to specify the correct axon morphology of these neurons and also regulates expression of glutamic acid decarboxylase, the rate limiting enzyme of GABA synthesis in these neurons. Moreover, lim-6 gene activity and GABA signaling regulate neuroendocrine outputs of the nervous system. In the chemosensory system lim-6 regulates the asymmetric expression of a probable chemosensory receptor. lim-6 is also required in epithelial cells for uterine morphogenesis. We compare the function of lim-6 to those of other LIM homeobox genes in C. elegans and suggest that LIM homeobox genes share the common theme of controlling terminal neural differentiation steps that when disrupted lead to specific neuroanatomical and neural function defects.

Download Full-text

Capillary-associated microglia regulate vascular structure and function through PANX1-P2RY12 coupling in mice

Nature Communications ◽

10.1038/s41467-021-25590-8 ◽

2021 ◽

Vol 12 (1) ◽

Cited By ~ 1

Author(s):

Kanchan Bisht ◽

Kenneth A. Okojie ◽

Kaushik Sharma ◽

Dennis H. Lentferink ◽

Yu-Yo Sun ◽

...

Keyword(s):

Myeloid Cell ◽

Structure And Function ◽

Pannexin 1 ◽

Vascular Physiology ◽

Blood Flow Increase ◽

Bona Fide ◽

Spatio Temporal ◽

And Function ◽

The Brain

AbstractMicroglia are brain-resident immune cells with a repertoire of functions in the brain. However, the extent of their interactions with the vasculature and potential regulation of vascular physiology has been insufficiently explored. Here, we document interactions between ramified CX3CR1 + myeloid cell somata and brain capillaries. We confirm that these cells are bona fide microglia by molecular, morphological and ultrastructural approaches. Then, we give a detailed spatio-temporal characterization of these capillary-associated microglia (CAMs) comparing them with parenchymal microglia (PCMs) in their morphological activities including during microglial depletion and repopulation. Molecularly, we identify P2RY12 receptors as a regulator of CAM interactions under the control of released purines from pannexin 1 (PANX1) channels. Furthermore, microglial elimination triggered capillary dilation, blood flow increase, and impaired vasodilation that were recapitulated in P2RY12−/− and PANX1−/− mice suggesting purines released through PANX1 channels play important roles in activating microglial P2RY12 receptors to regulate neurovascular structure and function.

Download Full-text

THE ANATOMY AND FUNCTION OF A SEGMENT OF THE X CHROMOSOME OF DROSOPHILA MELANOGASTER

Genetics ◽

10.1093/genetics/71.1.139 ◽

1972 ◽

Vol 71 (1) ◽

pp. 139-156

Author(s):

B H Judd ◽

M W Shen ◽

T C Kaufman

Keyword(s):

Drosophila Melanogaster ◽

X Chromosome ◽

Functional Group ◽

Deletion Mapping ◽

Mutant Type ◽

Functional Units ◽

Average Size ◽

And Function

ABSTRACT An average size chromomere of the polytene X chromosome of Drosophila melanogaster contains enough DNA in each haploid equivalent strand to code for 30 genes, each 1,000 nucleotides long. We have attempted to learn about the organization of chromosomes by asking how many functional units can be localized within a chromomere. This was done by 1) recovery of mutants representative of every cistron in the 3A2-3C2 region; 2) the characterization of the function of each mutant type and grouping by complementation tests; 3) the determination of the genetic and cytological position of each cistron by recombination and deletion mapping. The data clearly show one functional group per chromomere. It is postulated that a chromomere is one cistron within which much of the DNA is regulatory in function.

Download Full-text

60 YEARS OF POMC: Lipotropin and beta-endorphin: a perspective

Journal of Molecular Endocrinology ◽

10.1530/jme-16-0033 ◽

2016 ◽

Vol 56 (4) ◽

pp. T13-T25 ◽

Cited By ~ 10

Author(s):

D G Smyth

Keyword(s):

Amino Acids ◽

Amino Acid ◽

Amino Acid Analysis ◽

Structure And Function ◽

Biologically Active ◽

Molecular Endocrinology ◽

And Function ◽

The Brain ◽

Quantitative Amino Acid Analysis

Many important fields of research had a humble origin. In the distant past, A J P Martin’s discovery that amino acids could be separated by paper chromatography and Moore and Stein’s use of columns for quantitative amino acid analysis provided the first steps towards the determination of structure in complex biologically active molecules. They opened the door to reveal the essential relationship that exists between structure and function. In molecular endocrinology, for example, striking advances have been made by chemists with their expertise in the identification of structure working with biologists who contributed valuable knowledge and experience. Advantage was gained from the convergence of different background, and it is notable that the whole is greater than the sum. In the determination of structure, it may be recalled that four of the world’s great pioneers (Archibald Martin, Rodney Porter, Fred Sanger and Vincent du Vigneaud) were acknowledged for their fundamental contributions when individually they were awarded the Nobel Prize. They foresaw that the identification of structure would prove of outstanding importance in the future. Indeed, study of the structures of β-endorphin and enkephalin and the different forms of opiate activity they engender has led to a transformation in our understanding of chemical transmission in the brain.

Download Full-text

Lysosomes and Brain Health

Annual Review of Neuroscience ◽

10.1146/annurev-neuro-080317-061804 ◽

2018 ◽

Vol 41 (1) ◽

pp. 255-276 ◽

Cited By ~ 16

Author(s):

Jaiprakash Sharma ◽

Alberto di Ronza ◽

Parisa Lotfi ◽

Marco Sardiello

Keyword(s):

Neuronal Plasticity ◽

Therapeutic Strategies ◽

Brain Health ◽

Developmental Needs ◽

Fundamental Properties ◽

System A ◽

Lysosomal System ◽

And Function ◽

The Brain

One of the fundamental properties of the cell is the capability to digest and remodel its own components according to metabolic and developmental needs. This is accomplished via the autophagy-lysosome system, a pathway of critical importance in the brain, where it contributes to neuronal plasticity and must protect nonreplaceable neurons from the potentially harmful accumulation of cellular waste. The study of lysosomal biogenesis and function in the context of common and rare neurodegenerative diseases has revealed that a dysfunctional autophagy-lysosome system is the shared nexus where multiple, interconnected pathogenic events take place. The characterization of pathways and mechanisms regulating the lysosomal system and autophagic clearance offers unprecedented opportunities for the development of polyvalent therapeutic strategies based on the enhancement of the autophagy-lysosome pathway to maintain cellular homeostasis and achieve neuroprotection.

Download Full-text

A Reevaluation of Chitosan-Decorated Nanoparticles to Cross the Blood-Brain Barrier

Membranes ◽

10.3390/membranes10090212 ◽

2020 ◽

Vol 10 (9) ◽

pp. 212 ◽

Cited By ~ 2

Author(s):

Hernán Cortés ◽

Sergio Alcalá-Alcalá ◽

Isaac H. Caballero-Florán ◽

Sergio A. Bernal-Chávez ◽

Arturo Ávalos-Fuentes ◽

...

Keyword(s):

Blood Brain Barrier ◽

Brain Barrier ◽

Brain Diseases ◽

Transport Systems ◽

Future Directions ◽

Blood Brain ◽

Dynamic Interface ◽

And Function ◽

The Brain

The blood-brain barrier (BBB) is a sophisticated and very selective dynamic interface composed of endothelial cells expressing enzymes, transport systems, and receptors that regulate the passage of nutrients, ions, oxygen, and other essential molecules to the brain, regulating its homeostasis. Moreover, the BBB performs a vital function in protecting the brain from pathogens and other dangerous agents in the blood circulation. Despite its crucial role, this barrier represents a difficult obstacle for the treatment of brain diseases because many therapeutic agents cannot cross it. Thus, different strategies based on nanoparticles have been explored in recent years. Concerning this, chitosan-decorated nanoparticles have demonstrated enormous potential for drug delivery across the BBB and treatment of Alzheimer’s disease, Parkinson’s disease, gliomas, cerebral ischemia, and schizophrenia. Our main objective was to highlight the high potential of chitosan adsorption to improve the penetrability through the BBB of nanoformulations for diseases of CNS. Therefore, we describe the BBB structure and function, as well as the routes of chitosan for crossing it. Moreover, we define the methods of decoration of nanoparticles with chitosan and provide numerous examples of their potential utilization in a variety of brain diseases. Lastly, we discuss future directions, mentioning the need for extensive characterization of proposed nanoformulations and clinical trials for evaluation of their efficacy.

Download Full-text

Interparticle Interactions in Dilute Solutions of Polyelectrolyte Complex Micelles

10.26434/chemrxiv.7905275.v1 ◽

2019 ◽

Author(s):

Hao Wu ◽

Jeffrey Ting ◽

Thomas Weiss ◽

Matthew Tirrell

Keyword(s):

Rational Design ◽

Polyelectrolyte Complex ◽

Dilute Solutions ◽

Interparticle Interactions ◽

Detailed Characterization ◽

Internal Structures ◽

Fundamental Understanding ◽

Complex Micelles

The application of dilute solutions of polyelectrolyte complex micelles for delivering therapeutic nucleic acids into disease sites has gained momentum. This letter reports a detailed characterization of PEC micelles in dilute solutions including their internal structures and the determination of the interparticle interactions. We found that the soft corona chains tethered on the surface of phase-separated complex domains are compressed when micelles come close, at which point a hard-sphere interaction takes over. These findings contribute to the fundamental understanding of the structure and space-filling constraints in the complexation-driven self-assemblies and advance the rational design of cationic polymer-based non-viral nanocarriers.

Download Full-text

Interparticle Interactions in Dilute Solutions of Polyelectrolyte Complex Micelles

10.26434/chemrxiv.7905275 ◽

2019 ◽

Author(s):

Hao Wu ◽

Jeffrey Ting ◽

Thomas Weiss ◽

Matthew Tirrell

Keyword(s):

Rational Design ◽

Polyelectrolyte Complex ◽

Dilute Solutions ◽

Interparticle Interactions ◽

Detailed Characterization ◽

Internal Structures ◽

Fundamental Understanding ◽

Complex Micelles

Download Full-text

Sex Differences in Cognition: The New Rise of Biologism

The Australian Educational and Developmental Psychologist ◽

10.1017/s0816512200026730 ◽

1993 ◽

Vol 10 (1) ◽

pp. 2-5

Author(s):

Lesley J. Rogers

Keyword(s):

Sex Differences ◽

Brain Structure ◽

Structure And Function ◽

Representation Of Women ◽

Brain Structure And Function ◽

Environmental Stimulation ◽

And Function ◽

The Brain

AbstractCurrently there is an increase in the number of articles published in scientific journals and in the popular scientific media that claim a biological basis for sex differences in cognition and in certain structures in the brain. It can be argued that there is over-emphasis on the differences rather than similarities between the sexes, but it is even more important to question the assumed causation of the differences. This paper discusses recent evidence for an interactive role of early experience and hormonal condition in determining sex differences in brain structure and function. Although early studies using rats were thought to show that the male sex hormone, testosterone, acts on the brain in early life to direct its differentiation into either the male or female form, it is know known that this result comes about indirectly by changing the mother’s behaviour towards the pups. The hormone does not act on the brain directly but rather it alters the environment in which the young animals are rasied and this, in turn, influences the development of the brain. Indeed, the brain is in dynamic register with its environment both during development and in adulthood. Other examples also show that old ideas of rigid biological determination of brain structure and function need to be laid aside.The hypotheses for hormonal causation of sex differences humans rely heavily, if not exclusively, on the earlier interpretation of the experiments with rats, and there seems to be resistance to changing these notions based on the new discoveries. Apparently, there is strong pressure to cling on to biological determinist theories for sex differences in behaviour, and this has profound effects on social and educational policy. For example, biological determinism has been used to justify under representation of women in certain professions. Realisation of the dramatic effects that environmental stimulation and learning can have on the development of brain and behaviour leads us to an optimistic position for social change towards equality for women.

Download Full-text

Codon-optimized TDP-43-mediated neurodegeneration in a Drosophila model for ALS/FTLD

10.1101/696963 ◽

2019 ◽

Author(s):

Tanzeen Yusuff ◽

Shreyasi Chatterjee ◽

Ya-Chu Chang ◽

Tzu-Kang Sang ◽

George R. Jackson

Keyword(s):

The Novel ◽

Genetic Screens ◽

Gain Of Function ◽

Function Mechanism ◽

Promoter Fusion ◽

Drosophila Model ◽

Weight Protein ◽

Photoreceptor Neurons ◽

And Function

ABSTRACTTransactive response DNA binding protein-43 (TDP-43) is known to mediate neurodegeneration associated with amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). The exact mechanism by which TDP-43 exerts toxicity in the brains of affected patients remains unclear. In a novel Drosophila melanogaster model, we report gain-of-function phenotypes due to misexpression of insect codon-optimized version of human wild-type TDP-43 (CO-TDP-43) using both the binary GAL4/UAS system and direct promoter fusion constructs. The CO-TDP-43 model showed robust tissue specific phenotypes in the adult eye, wing, and bristles in the notum. Compared to non-codon optimized transgenic flies, the CO-TDP-43 flies produced increased amount of high molecular weight protein, exhibited pathogenic phenotypes, and showed cytoplasmic aggregation with both nuclear and cytoplasmic expression of TDP-43. Further characterization of the adult retina showed a disruption in the morphology and function of the photoreceptor neurons with the presence of acidic vacuoles that are characteristic of autophagy. Based on our observations, we propose that TDP-43 has the propensity to form toxic protein aggregates via a gain-of-function mechanism, and such toxic overload leads to activation of protein degradation pathways such as autophagy. The novel codon optimized TDP-43 model is an excellent resource that could be used in genetic screens to identify and better understand the exact disease mechanism of TDP-43 proteinopathies and find potential therapeutic targets.

Download Full-text