Development Diseases Research Articles

The role of Wnt, ARL4C, and Sema3A in developmental process and disease pathogenesis.

Various types of tumors, including malignant and benign ones, occur in the oral cavity. These arise from the mucosal epithelium, odontogenic epithelium, and salivary gland. To date, few major driver events in oral tumors have been identified. Accordingly, molecular targets in anti-tumor therapy for oral tumors are lacking. We focused on elucidating the function of aberrantly activated signal transduction related to oral tumor formation, especially in oral squamous cell carcinoma, ameloblastoma, and adenoid cystic carcinoma, which are raised as common oral tumors. Wnt/β-catenin-dependent pathway is involved in the developmental process, organ homeostasis and disease pathogenesis through regulating various cellular functions by enhancing transcriptional activity. Recently, we identified ADP-ribosylation factor (ARF)-like 4c (ARL4C) and Semaphorin 3A (Sema3A), the expression of which is regulated by Wnt/β-catenin-dependent pathway, and characterized their functions in the developmental process and tumor formation. This review highlights the recent advances in understanding the roles of Wnt/β-catenin-dependent pathway, ARL4C and Sema3A, as determined by pathological and experimental studies.

CHD-associated enhancers shape human cardiomyocyte lineage commitment.

Enhancers orchestrate gene expression programs that drive multicellular development and lineage commitment. Thus, genetic variants at enhancers are thought to contribute to developmental diseases by altering cell fate commitment. However, while many variant-containing enhancers have been identified, studies to endogenously test the impact of these enhancers on lineage commitment have been lacking. We perform a single-cell CRISPRi screen to assess the endogenous roles of 25 enhancers and putative cardiac target genes implicated in genetic studies of congenital heart defects (CHDs). We identify 16 enhancers whose repression leads to deficient differentiation of human cardiomyocytes (CMs). A focused CRISPRi validation screen shows that repression of TBX5 enhancers delays the transcriptional switch from mid- to late-stage CM states. Endogenous genetic deletions of two TBX5 enhancers phenocopy epigenetic perturbations. Together, these results identify critical enhancers of cardiac development and suggest that misregulation of these enhancers could contribute to cardiac defects in human patients.

The role of noncoding RNAs in pancreatic birth defects.

Congenital defects in the pancreas can cause severe health issues such as pancreatic cancer and diabetes which require lifelong treatment. Regenerating healthy pancreatic cells to replace malfunctioning cells has been considered a promising cure for pancreatic diseases including birth defects. However, such therapies are currently unavailable in the clinic. The developmental gene regulatory network underlying pancreatic development must be reactivated for in vivo regeneration and recapitulated in vitro for cell replacement therapy. Thus, understanding the mechanisms driving pancreatic development will pave the way for regenerative therapies. Pancreatic progenitor cells are the precursors of all pancreatic cells which use epigenetic changes to control gene expression during differentiation to generate all of the distinct pancreatic cell types. Epigenetic changes involving DNA methylation and histone modifications can be controlled by noncoding RNAs (ncRNAs). Indeed, increasing evidence suggests that ncRNAs are indispensable for proper organogenesis. Here, we summarize recent insight into the role of ncRNAs in the epigenetic regulation of pancreatic development. We further discuss how disruptions in ncRNA biogenesis and expression lead to developmental defects and diseases. This review summarizes in vivo data from animal models and in vitro studies using stem cell differentiation as a model for pancreatic development.

Assessment of mandibular condylar morphology through digital panoramic radiograph: A radiographic study

The temporomandibular joint is one of the most intricate human articulations (TMJ). Each joint is made up of a mandibular condyle and its associated temporal cavity (glenoid fossa and articular eminence). Human mandibular condyle morphology can be divided into six types: Type I: Oval; Type II: Flattened; Type III: Diamond; Type IV: Crooked finger; Type V:Bifid and Type VI: Bird beak. The mandibular condyle appears in several different age groups and individuals in many distinct ways. Condyle remodelling to account for developmental variations, malocclusion, trauma, and other developmental illnesses and diseases are all examples of developmental disorders and diseases that can result from simple developmental variability. Panoramic radiography has been recommended as a screening tool for TMJ patients, and it may be useful to spot major bone abnormalities in the condyle.: The aim of the current study is to observe and record the variations in condyle forms in Punjab (North India) using an Orthopantomographs (OPGs), which were crucial for patient treatment in several branches of dentistry. This retrospective study comprised radiographic evaluation of 400 condylar heads after visualising 200 digitalised OPGs taken for routine investigation. The most common shape of condyle on right observed was oval (43.5%) followed by Bird Beak (20.5%), Diamond (12.5%), Flattened (12%), Crooked finger(6.5%) and Bifid (5%). The most common shape of condyle on left observed was Oval (51%) followed by Bird Beak (15%), Diamond (14%), Flattened (9%), Crooked finger(8%) and Bifid (3%). In Males, the commonest form of left and right condylar morphology was and the least form of right condylar morphology was , whereas the least form of left condylar morphology observed was and In Females, the commonest form of left and right condylar morphology was and the least form of left and right condylar morphology observed was The aim of this study was to determine the most typical radiographic forms of the mandibular condyle on the OPG. Six various condyle shapes—Oval, Flattened, Bird beak, Diamond, Crooked finger, and bifid—have been identified in the current study, with the oval form being the most prevalent on both sides and in both sexes. Bifid is the least typical shape for the right and left condyles.

Surgical Strategy for Hemispherotomy.

Hemispherotomy is a radical treatment for drug-resistant epilepsy that targets developmental, acquired, and progressive diseases with widespread epileptogenic regions in one cerebral hemisphere. Currently, two main approaches are utilized after repeated improvements: lateral and vertical approaches. With the lateral approach, the surgical field is wide, and the approach to the lateral ventricle is relatively easy. On the other hand, the vertical approach has the advantage of reducing intraoperative bleeding and operating time as the resection line of the radial fiber is short, and understanding the three-dimensional anatomy is relatively easy. The lateral approach is generally used for atrophic lesions, whereas the vertical approach is for hypertrophic lesions. Hemispherotomy is expected to not only suppress epileptic seizures but also improve psychomotor development by protecting the unaffected cerebral hemisphere. However, this method is one of the most invasive surgeries in epilepsy surgery, and it is important to fully consider its indications. Furthermore, understanding the neural fiber pathway is important for actual surgery.

CLINICAL CASE OF CUTIS VERTICIS GYRATA

Cutis verticis gyrata (CVG) is a descriptive term for a rare benign skin condition characterized by the formation of tortuous folds and deep furrows that mimic the gyri of the brain because of excessive skin growth. It is observed mainly in men. The first clinical case of the disease was described in 1837 by Alibert J.
 There are primary and secondary forms of CVG. Among the cases of primary CVG in 1984, Garden JM and Robinson JK further distinguished the essential and combined subtypes. The reason for the appearance of the essential form is not known. Primary combined CVG can accompany neuropsychiatric disorders, cerebral palsy, epilepsy, seizures, and ophthalmological abnormalities, most commonly cataracts. Secondary CVG occurs as a result of chronic inflammation, such as hysteria, lymphostasis, elephantiasis, eczema, psoriasis, folliculitis, atopic dermatitis, etc. In case of secondary CVG, the lower extremities are more often affected, the skin is congested-red, cyanotic, dense, swollen. Papillomatous growths, layering of crusts and scales are often visible against the background of changed skin.
 Given the rarity of this disease (it was diagnosed for the first time in our more than 50 years of dermatological practice), we report a clinical case of CVG.
 Case Presentation. Patient P., 27 years old, complained of wrinkles and increased mobility of the skin of the scalp. He noticed the first manifestations of the disease at the age of 17, but did not pay attention, believing that these were individual features of the skin structure. For the last 3-4 years in a row, he noticed a thickening and increase in the size of the folds of the skin on the scalp, growing mobility. The skin, according to the patient, had the appearance of ribs.
 During the dermatological examination, the skin is of normal color, turgor and elasticity are preserved, sweat and sebum secretion is moderate. Skin appendages are without pathological changes. The skin of the scalp is uniformly covered with thick hair, hyperelastic, pronounced transverse deep linear furrows resembling brain convolutions are visible.
 When using dermoscopy without a light-conducting liquid, the vascular pattern is hardly visible, on the surface there is small lamellar peeling. However, after its application, areas of clearly visible vessels of the superficial vascular plexus of the skin, which coincide with the location of the furrows, are determined.
 The patient was examined; no pathology was detected on the part of internal organs and heart. The results of ultrasound of the thyroid gland and organs of the abdominal cavity were without pathological changes. General analysis of blood, urine, blood sugar within the normal range. Biochemical indicators of liver and kidney function without deviations. The patient is recommended to have a periodic examination by a dermatologist. With increasing clinical manifestations - surgical removal of skin folds.
 Conclusions. The described clinical case of CVG is of considerable interest to dermatologists, pediatricians, and geneticists as a rare new developmental disease. In our report, the clinical picture of changes on the skin is illustrated, and differential diagnosis with dermatoses that are closest in clinical manifestations is briefly carried out.

Full-length circular RNA profiling by nanopore sequencing with CIRI-long.

Circular RNAs (circRNAs) have important roles in regulating developmental processes and disease progression. As most circRNA sequences are highly similar to their cognate linear transcripts, the current short-read sequencing-based methods rely on the back-spliced junction signal for distinguishing circular and linear reads, which does not allow circRNAs' full-length structure to be effectively reconstructed. Here we describe a long-read sequencing-based protocol, CIRI-long, for the detection of full-length circular RNAs. The CIRI-long protocol combines rolling circular reverse transcription and nanopore sequencing to capture full-length circRNA sequences. After poly(A) tailing, RNase R treatment, and size selection of polymerase chain reaction products, CIRI-long achieves an increased percentage (6%) of circular reads in the constructed library, which is 20-fold higher compared with previous Illumina-based strategies. This method can be applied in cell lines or tissue samples, enabling accurate detection of full-length circRNAs in the range of 100-3,000 bp. The entire protocol can be completed in 1 d, and can be scaled up for large-scale analysis using the nanopore barcoding kit and PromethION sequencing device. CIRI-long can serve as an effective and user-friendly protocol for characterizing full-length circRNAs, generating direct and convincing evidence for the existence of detected circRNAs. The analytical pipeline offers convenient functions for identification of full-length circRNA isoforms and integration of multiple datasets. The assembled full-length transcripts and their splicing patterns provide indispensable information to explore the biological function of circRNAs.

Abstract 1428: Luminescent immunoassays for homogeneous determination of cell proliferation and senescence

Abstract We have developed homogeneous, luminescent immunoassays for simple and rapid determination of Ki-67 and uPAR levels in 96-well format, thereby enabling efficient and quantitative assessment of proliferation and senescence in mammalian cell culture. Assessment of proliferative capacity is of key importance in numerous research areas, including cancer and various proliferative disorders, assessment of cell fitness (e.g., T cell fitness, stem cell characterization), and evaluation of test compound or drug effects. Cell senescence, characterized in part by loss of proliferative capacity, is an altered, proinflammatory state of cells induced in response to developmental ques, aging, disease, or acute stressors typically involving DNA damage. Ki-67 is a nuclear protein widely used as a marker of proliferation due to its pervasive expression in cycling cells but absence from non-dividing (G0) cells, whether quiescent, senescent, or terminally differentiated. In contrast, urokinase plasminogen activator receptor (uPAR) is a cell-surface protein whose expression was recently reported to increase significantly with the induction of senescence. Of note, commonly used assays of Ki-67 and uPAR levels typically rely upon non-homogeneous methods, including imaging, flow cytometry, or western blotting. Application of Lumit™ technology enabled our development of no-transfer, no-wash immunoassays for Ki-67 (lytic) and uPAR (nonlytic) determinations directly in cell wells. Treatment of human CD8+ T cells with CD3/CD28 T cell activator produced more than a 10-fold upregulation of Ki-67 levels, consistent with induction of T cell proliferation. In contrast, treatment of HCT116 colorectal cancer cells for 48 h with the antiproliferative compounds doxorubicin (100 nM) and nutlin-3A (10 μM) produced 65% and 90% reductions, respectively, in Ki-67 levels normalized to a measure of viable cell number, consistent with their relative antiproliferative activities. Dose-dependent treatment of HCT116 cells with nutlin-3A for 24 and 48 h produced 69% and 93% reduction, respectively, in normalized Ki-67 levels with a potency of ~2.5 μM. Treatment of HCT116 and A549 cancer cell lines for 72 h with 10-20 μM nutlin-3A, in addition to causing profound reduction in Ki-67 levels and loss of proliferative capacity, produced 2.3- to 4-fold increases in cell-surface uPAR levels, reflective of the emergence of the senescence phenotype. These luminescent, homogeneous Ki-67 and uPAR immunoassays provide an efficient means to quantitatively assess changes in cell proliferation and senescence in cell culture models for basic research and drug discovery applications. Citation Format: Dan F. Lazar, Kevin R. Kupcho, Andrew L. Niles, James J. Cali. Luminescent immunoassays for homogeneous determination of cell proliferation and senescence [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1428.

Joint pain and mobility

This workshop discussed the diagnosis of developmental joint disease and degenerative conditions in dogs and cats, and looked at a multimodal approach to managing pain caused by these conditions, which involves surgery, pain medication, physical therapy, exercise and lifestyle modifications, weight management and joint supplements. It also considers how best to help owners manage these conditions.

Paediatric Pulmonary hypertension

Pulmonary hypertension (PH) is a rare disease in newborns, infants, and children that is associated with significant morbidity and mortality. In the majority of pediatric patients, PH is idiopathic or associated with congenital heart disease and rarely is associated with other conditions such as connective tissue or thromboembolic disease. Incidence data from the Netherlands has revealed an annual incidence and point prevalence of 0.7 and 4.4 for idiopathic pulmonary arterial hypertension and 2.2 and 15.6 for pulmonary arterial hypertension, respectively, associated with congenital heart disease (CHD) cases per million children. The updated Nice classification for PH has been enhanced to include a greater depth of CHD and emphasizes persistent PH of the newborn and developmental lung diseases, such as bronchopulmonary dysplasia and congenital diaphragmatic hernia. The management of pediatric PH remains challenging because treatment decisions continue to depend largely on results from evidence based adult studies and the clinical experience of pediatric experts. (J Am Coll Cardiol 2013;62:D117-26) ©2013 by the American College of Cardiology Foundation.

Ribonuclease inhibitor 1 (RNH1) deficiency cause congenital cataracts and global developmental delay with infection-induced psychomotor regression and anemia

Ribonuclease inhibitor 1, also known as angiogenin inhibitor 1, encoded by RNH1, is a ubiquitously expressed leucine-rich repeat protein, which is highly conserved in mammalian species. Inactivation of rnh1 in mice causes an embryonically lethal anemia, but the exact biological function of RNH1 in humans remains unknown and no human genetic disease has so far been associated with RNH1. Here, we describe a family with two out of seven siblings affected by a disease characterized by congenital cataract, global developmental delay, myopathy and psychomotor deterioration, seizures and periodic anemia associated with upper respiratory tract infections. A homozygous splice-site variant (c.615-2A > C) in RNH1 segregated with the disease. Sequencing of RNA derived from patient fibroblasts and cDNA analysis of skeletal muscle mRNA showed aberrant splicing with skipping of exon 7. Western blot analysis revealed a total lack of the RNH1 protein. Functional analysis revealed that patient fibroblasts were more sensitive to RNase A exposure, and this phenotype was reversed by transduction with a lentivirus expressing RNH1 to complement patient cells. Our results demonstrate that loss-of-function of RNH1 in humans is associated with a multiorgan developmental disease with recessive inheritance. It may be speculated that the infection-induced deterioration resulted from an increased susceptibility toward extracellular RNases and/or other inflammatory responses normally kept in place by the RNase inhibitor RNH1.

Disrupting cortical astrocyte Ca2+ signaling in developing brain induces social deficits and depressive-like behaviors.

Astrocytes are present throughout the central nervous system and display complex intracellular Ca2+ signals. However, it is largely unknown regarding how astrocytic Ca2+ signals regulate neural microcircuits in developing brain and mammalian behavior in vivo. In this study, we specifically overexpressed the plasma membrane calcium-transporting ATPase2 (PMCA2) of cortical astrocytes and used immunohistochemistry, Ca2+ imaging, electrophysiology, and behavioral tests to investigate the effects of genetically reducing cortical astrocyte Ca2+ signaling during a critical developmental period in vivo. We found that reducing cortical astrocyte Ca2+ signaling during development led to social interaction deficits, depressive-like behaviors, and abnormal synaptic structure and transmission. In addition, restoring cortical astrocyte Ca2+ signaling using chemogenetic activation of Gq-coupled designer receptors exclusively activated by designer drugs rescued these synaptic and behavioral deficits. Together, our data demonstrate that the integrity of cortical astrocyte Ca2+ signaling in developing mice is critical for neural circuit development and may be involved in the pathogenesis of developmental neuropsychiatric diseases, such as autism spectrum disorders and depression.

Decellularized Extracellular Matrix for Remodeling Bioengineering Organoid's Microenvironment.

Over the past decade, stem cell- and tumor-derived organoids are the most promising models in developmental biology and disease modeling, respectively. The matrix is one of three main elements in the construction of an organoid and the most important module of its extracellular microenvironment. However, the source of the currently available commercial matrix, Matrigel, limits the application of organoids in clinical medicine. It is worth investigating whether the original decellularized extracellular matrix (dECM) can be exploited as the matrix of organoids and improving organoid construction are very important. In this review, tissue decellularization protocols and the characteristics of decellularization methods, the mechanical support and biological cues of extraccellular matrix (ECM), methods for construction of multifunctional dECM and responsive dECM hydrogel, and the potential applications of functional dECM are summarized. In addition, some expectations are provided for dECM as the matrix of organoids in clinical applications.

Circular RNAs in the Origin of Developmental Lung Disease: Promising Diagnostic and Therapeutic Biomarkers

Circular RNA (circRNA) is a newly discovered noncoding RNA that regulates gene transcription, binds to RNA-related proteins, and encodes protein microRNAs (miRNAs). The development of molecular biomarkers such as circRNAs holds great promise in the diagnosis and prognosis of clinical disorders. Importantly, circRNA-mediated maternal-fetus risk factors including environmental (high altitude), maternal (preeclampsia, smoking, and chorioamnionitis), placental, and fetal (preterm birth and low birth weight) factors are the early origins and likely to contribute to the occurrence and progression of developmental and pediatric cardiopulmonary disorders. Although studies of circRNAs in normal cardiopulmonary development and developmental diseases have just begun, some studies have revealed their expression patterns. Here, we provide an overview of circRNAs' biogenesis and biological functions. Furthermore, this review aims to emphasize the importance of circRNAs in maternal-fetus risk factors. Likewise, the potential biomarker and therapeutic target of circRNAs in developmental and pediatric lung diseases are explored.

Bilateral osteochondrosis of the distal tibial epiphysis: An extremely rare condition: Case report with literature review

Osteochondrosis is a developmental disease characterized by an abnormal endochondral ossification of the epiphyses or epiphyseal equivalents (round bones and apophyses). Distal tibial epiphysis is an uncommon location of this condition and bilateral involvement is extremely rare

Primary human organoids models: Current progress and key milestones.

During the past 10years the world has experienced enormous progress in the organoids field. Human organoids have shown huge potential to study organ development, homeostasis and to model diseases in vitro. The organoid technology has been widely and increasingly applied to generate patient-specific in vitro 3D cultures, starting from both primary and reprogrammed stem/progenitor cells. This has consequently fostered the development of innovative disease models and new regenerative therapies. Human primary, or adult stem/progenitor cell-derived, organoids can be derived from both healthy and pathological primary tissue samples spanning from fetal to adult age. The resulting 3D culture can be maintained for several months and even years, while retaining and resembling its original tissue's properties. As the potential of this technology expands, new approaches are emerging to further improve organoid applications in biology and medicine. This review discusses the main organs and tissues which, as of today, have been modelled in vitro using primary organoid culture systems. Moreover, we also discuss the advantages, limitations, and future perspectives of primary human organoids in the fields of developmental biology, disease modelling, drug testing and regenerative medicine.

Defects in placental syncytiotrophoblast cells are a common cause of developmental heart disease

Placental abnormalities have been sporadically implicated as a source of developmental heart defects. Yet it remains unknown how often the placenta is at the root of congenital heart defects (CHDs), and what the cellular mechanisms are that underpin this connection. Here, we selected three mouse mutant lines, Atp11a, Smg9 and Ssr2, that presented with placental and heart defects in a recent phenotyping screen, resulting in embryonic lethality. To dissect phenotype causality, we generated embryo- and trophoblast-specific conditional knockouts for each of these lines. This was facilitated by the establishment of a new transgenic mouse, Sox2-Flp, that enables the efficient generation of trophoblast-specific conditional knockouts. We demonstrate a strictly trophoblast-driven cause of the CHD and embryonic lethality in one of the three lines (Atp11a) and a significant contribution of the placenta to the embryonic phenotypes in another line (Smg9). Importantly, our data reveal defects in the maternal blood-facing syncytiotrophoblast layer as a shared pathology in placentally induced CHD models. This study highlights the placenta as a significant source of developmental heart disorders, insights that will transform our understanding of the vast number of unexplained congenital heart defects.

Biochemical Studies of Systemic Lupus Erythematosus-Associated Mutations in Nonreceptor Tyrosine Kinases Ack1 and Brk.

Tyrosine kinases (TKs) play essential roles in signaling processes that regulate cell survival, migration, and proliferation. Dysregulation of tyrosine kinases underlies many disorders, including cancer, cardiovascular and developmental diseases, as well as pathologies of the immune system. Ack1 and Brk are nonreceptor tyrosine kinases (NRTKs) best known for their roles in cancer. Here, we have biochemically characterized novel Ack1 and Brk mutations identified in patients with systemic lupus erythematosus (SLE). These mutations are the first SLE-linked polymorphisms found among NRTKs. We show that two of the mutants are catalytically inactive, while the other three have reduced activity. To understand the structural changes associated with the loss-of-function phenotype, we solved the crystal structure of one of the Ack1 kinase mutants, K161Q. Furthermore, two of the mutated residues (Ack1 A156 and K161) critical for catalytic activity are highly conserved among other TKs, and their substitution in other members of the kinase family could have implications in cancer. In contrast to canonical gain-of-function mutations in TKs observed in many cancers, we report loss-of-function mutations in Ack1 and Brk, highlighting the complexity of TK involvement in human diseases.

Organoid intelligence (OI): the new frontier in biocomputing and intelligence-in-a-dish

Recent advances in human stem cell-derived brain organoids promise to replicate critical molecular and cellular aspects of learning and memory and possibly aspects of cognition in vitro. Coining the term “organoid intelligence” (OI) to encompass these developments, we present a collaborative program to implement the vision of a multidisciplinary field of OI. This aims to establish OI as a form of genuine biological computing that harnesses brain organoids using scientific and bioengineering advances in an ethically responsible manner. Standardized, 3D, myelinated brain organoids can now be produced with high cell density and enriched levels of glial cells and gene expression critical for learning. Integrated microfluidic perfusion systems can support scalable and durable culturing, and spatiotemporal chemical signaling. Novel 3D microelectrode arrays permit high-resolution spatiotemporal electrophysiological signaling and recording to explore the capacity of brain organoids to recapitulate the molecular mechanisms of learning and memory formation and, ultimately, their computational potential. Technologies that could enable novel biocomputing models via stimulus-response training and organoid-computer interfaces are in development. We envisage complex, networked interfaces whereby brain organoids are connected with real-world sensors and output devices, and ultimately with each other and with sensory organ organoids (e.g. retinal organoids), and are trained using biofeedback, big-data warehousing, and machine learning methods. In parallel, we emphasize an embedded ethics approach to analyze the ethical aspects raised by OI research in an iterative, collaborative manner involving all relevant stakeholders. The many possible applications of this research urge the strategic development of OI as a scientific discipline. We anticipate OI-based biocomputing systems to allow faster decision-making, continuous learning during tasks, and greater energy and data efficiency. Furthermore, the development of “intelligence-in-a-dish” could help elucidate the pathophysiology of devastating developmental and degenerative diseases (such as dementia), potentially aiding the identification of novel therapeutic approaches to address major global unmet needs.

Microtubule-associated proteins and enzymes modifying tubulin.

Microtubules (MTs) are essential for many cellular processes including establishment of cell shape and polarity, chromosome segregation, vesicle transport, and nuclear positioning. Human cells express 22 tubulin isoforms that have both overlapping and distinctive functions. Tubulins reversely polymerize to form cylindrical MTs, while MT-associated proteins (MAPs), posttranslational modifications (PTMs), and mechanical forces regulate their functions. To help both tubulin researchers and medicinal chemists, this review article lists 489 MAPs, 43 known enzymes that mediate PTMs, and 306 drugs that influence the functions of MTs and MAPs and discusses recent microtubule research. Readers are able to sort the list based on name, size, functions, related human diseases, and date of discovery. The list also contains links to Uniprot and Protein Atlas databases to access further details such as protein structure, associated proteins, subcellular localization, expression levels in cells and tissues, mutations, and pathology. Because the microtubule cytoskeleton is involved in many pathological processes such as tumorigenesis, invasion, and developmental diseases, small molecules that target on MT and MAPs hold potential to treat these diseases and are also listed.