scholarly journals Lessons on gene regulation learnt from the Drosophila melanogaster bithorax complex

2020 ◽  
Vol 64 (1-2-3) ◽  
pp. 151-158
Author(s):  
Arumugam Srinivasan ◽  
Rakesh K. Mishra

Homeotic or Hox genes determine the anterior-posterior body axis in all bilaterians. As expected, Hox genes are highly conserved across bilaterians. Interestingly, however, the peculiar organization of Hox genes in the form of clusters where the order of occurrence of genes in the genome corresponds to the order in which they regulate segmental identity of anterior-posterior body axis is also conserved. The relation between collinearity of arrangement of genes on the chromosomes and spatial function along the body axis has attracted attention to exploring its relevance in the precise regulation of Hox genes. Conservation of genes and their arrangement suggests a linkage between co-regulation and the higher order chromatin organization of the entire complex. To this end, we and others have used Drosophila as the model system to understand the cis-and trans-regulatory components of Hox genes. A number of chromatin-level regulatory elements, like chromatin domain boundaries, and Polycomb Response Elements (PREs) have been discovered in this process. Interestingly, much of what has emerged from the study of homeotic genes, the cis-elements and protein factors, have relevance across the genome in a large number of regulatory events beyond the Hox genes. Here, we review our findings and discuss their genome-wide implications in complex regulatory processes.

Development ◽  
1992 ◽  
Vol 116 (3) ◽  
pp. 543-554 ◽  
Author(s):  
U. Hinz ◽  
A. Wolk ◽  
R. Renkawitz-Pohl

beta 3 tubulin expression accompanies the specification and differentiation of the Drosophila mesoderm. The genetic programs involved in these processes are largely unknown. Our previous studies on the regulation of the beta 3 tubulin gene have shown that upstream sequences guide the expression in the somatic musculature, while regulatory elements in the first intron are necessary for expression in the visceral musculature. To further analyse this mode of regulation, which reflects an early embryonic specification program, we undertook a more detailed analysis of the regulatory capabilities of the intron. The results reveal not only a certain degree of redundancy in the cis-acting elements, which act at different developmental stages in the same mesodermal derivatives, but they also demonstrate in the visceral mesoderm, which forms a continuous epithelium along the body axis of the embryo, an early action of regulators guiding gene expression along the anterior-posterior axis of the embryo: an enhancer element in the intron leads to expression in a subdomain restricted along the anterior-posterior axis. This pattern is altered in mutants in the homeotic gene Ultrabithorax (Ubx), whereas ectopic Ubx expression leads to activity of the enhancer in the entire visceral mesoderm. So this element is likely to be a target of homeotic genes, which would define the beta 3 tubulin gene as a realisator gene under the control of selector genes.


Development ◽  
1995 ◽  
Vol 121 (2) ◽  
pp. 333-346 ◽  
Author(s):  
A.C. Burke ◽  
C.E. Nelson ◽  
B.A. Morgan ◽  
C. Tabin

A common form of evolutionary variation between vertebrate taxa is the different numbers of segments that contribute to various regions of the anterior-posterior axis; cervical vertebrae, thoracic vertebrae, etc. The term ‘transposition’ is used to describe this phenomenon. Genetic experiments with homeotic genes in mice have demonstrated that Hox genes are in part responsible for the specification of segmental identity along the anterior-posterior axis, and it has been proposed that an axial Hox code determines the morphology of individual vertebrae (Kessel, M. and Gruss, P. (1990) Science 249, 347–379). This paper presents a comparative study of the developmental patterns of homeobox gene expression and developmental morphology between animals that have homologous regulatory genes but different morphologies. The axial expression boundaries of 23 Hox genes were examined in the paraxial mesoderm of chick, and 16 in mouse embryos by in situ hybridization and immunolocalization techniques. Hox gene anterior expression boundaries were found to be transposed in concert with morphological boundaries. This data contributes a mechanistic level to the assumed homology of these regions in vertebrates. The recognition of mechanistic homology supports the historical homology of basic patterning mechanisms between all organisms that share these genes.


2018 ◽  
Author(s):  
Titus Ponrathnam ◽  
Rakesh K Mishra

AbstractHomeotic genes are the key early determinants of cell identity along the anterior-posterior body axis across bilaterians. More recently, however, several late non-homeotic functions of hox genes have emerged in a variety of organogenesis processes, including in mammals. Being crucial factors in determining cell identity and organogenesis, the misregulation of hox genes is likely to be associated with defects in these processes. Several studies have reported misexpression of hox genes in a variety of malignancies including acute myeloid leukaemia. Considering thatDrosophilais a well-established model for the study of haematopoiesis, we ectopically expressed the hox genes,Dfd,Ubx,abd-AandAbd-B, to ask if and how it will alter the process of haematopoiesis. We observed black melanised spots circulating in the viscera of the larvae and extensive lethality at during the pupal stage in these conditions. Such abnormalities are the hallmark of dysregulated haematopoiesis. We also observed an increase in blood cell number as well as their enhanced differentiation into lamellocytes. Our study opens a new possibility of addressing the function hox genes in normal and leukemogenic hematopoiesis with potential implications in downstream targets for diagnostic markers and therapy.SummaryDrosophilaHox genes, when expressed in blood cells, are leukemogenic, induce cell autonomous proliferation and differentiation. This reinforces previous studies in vertebrates and allows for Hox induced leukaemia to be studied inDrosophila.


Author(s):  
Nikhil Hajirnis ◽  
Rakesh K. Mishra

Hox genes code for transcription factors and are evolutionarily conserved. They regulate a plethora of downstream targets to define the anterior-posterior (AP) body axis of a developing bilaterian embryo. Early work suggested a possible role of clustering and ordering of Hox to regulate their expression in a spatially restricted manner along the AP axis. However, the recent availability of many genome assemblies for different organisms uncovered several examples that defy this constraint. With recent advancements in genomics, the current review discusses the arrangement of Hox in various organisms. Further, we revisit their discovery and regulation in Drosophila melanogaster. We also review their regulation in different arthropods and vertebrates, with a significant focus on Hox expression in the crustacean Parahyale hawaiensis. It is noteworthy that subtle changes in the levels of Hox gene expression can contribute to the development of novel features in an organism. We, therefore, delve into the distinct regulation of these genes during primary axis formation, segment identity, and extra-embryonic roles such as in the formation of hair follicles or misregulation leading to cancer. Toward the end of each section, we emphasize the possibilities of several experiments involving various organisms, owing to the advancements in the field of genomics and CRISPR-based genome engineering. Overall, we present a holistic view of the functioning of Hox in the animal world.


Genetics ◽  
2020 ◽  
Vol 217 (1) ◽  
Author(s):  
Yuji Matsuoka ◽  
Antónia Monteiro

Abstract The eyespot patterns found on the wings of nymphalid butterflies are novel traits that originated first in hindwings and subsequently in forewings, suggesting that eyespot development might be dependent on Hox genes. Hindwings differ from forewings in the expression of Ultrabithorax (Ubx), but the function of this Hox gene in eyespot development as well as that of another Hox gene Antennapedia (Antp), expressed specifically in eyespots centers on both wings, are still unclear. We used CRISPR-Cas9 to target both genes in Bicyclus anynana butterflies. We show that Antp is essential for eyespot development on the forewings and for the differentiation of white centers and larger eyespots on hindwings, whereas Ubx is essential not only for the development of at least some hindwing eyespots but also for repressing the size of other eyespots. Additionally, Antp is essential for the development of silver scales in male wings. In summary, Antp and Ubx, in addition to their conserved roles in modifying serially homologous segments along the anterior–posterior axis of insects, have acquired a novel role in promoting the development of a new set of serial homologs, the eyespot patterns, in both forewings (Antp) and hindwings (Antp and Ubx) of B. anynana butterflies. We propose that the peculiar pattern of eyespot origins on hindwings first, followed by forewings, could be due to an initial co-option of Ubx into eyespot development followed by a later, partially redundant, co-option of Antp into the same network.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shotaro Harada ◽  
Takao Imai ◽  
Yasumitsu Takimoto ◽  
Yumi Ohta ◽  
Takashi Sato ◽  
...  

AbstractIn the interaural direction, translational linear acceleration is loaded during lateral translational movement and gravitational acceleration is loaded during lateral tilting movement. These two types of acceleration induce eye movements via two kinds of otolith-ocular reflexes to compensate for movement and maintain clear vision: horizontal eye movement during translational movement, and torsional eye movement (torsion) during tilting movement. Although the two types of acceleration cannot be discriminated, the two otolith-ocular reflexes can distinguish them effectively. In the current study, we tested whether lateral-eyed mice exhibit both of these otolith-ocular reflexes. In addition, we propose a new index for assessing the otolith-ocular reflex in mice. During lateral translational movement, mice did not show appropriate horizontal eye movement, but exhibited unnecessary vertical torsion-like eye movement that compensated for the angle between the body axis and gravito-inertial acceleration (GIA; i.e., the sum of gravity and inertial force due to movement) by interpreting GIA as gravity. Using the new index (amplitude of vertical component of eye movement)/(angle between body axis and GIA), the mouse otolith-ocular reflex can be assessed without determining whether the otolith-ocular reflex is induced during translational movement or during tilting movement.


Development ◽  
1994 ◽  
Vol 120 (5) ◽  
pp. 1035-1047 ◽  
Author(s):  
M.A. Herman ◽  
H.R. Horvitz

The generation and orientation of cellular and organismic polarity are fundamental aspects of development. Mutations in the gene lin-44 of the nematode Caenorhabditis elegans reverse both the relative positions of specific sister cells and the apparent polarities of these cells. Thus, lin-44 mutants appear to generate polar cells but to misorient these cells along the body axis of the animal. We postulate that lin-44 acts to specify the orientation of polar cells.


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