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Indian Journal of Dermatology,... 2022Ras/mitogen-activated protein kinase pathway dysregulation results in a group of disorders, collectively termed as RASopathies. Neurofibromatosis type 1, Noonan... (Review)
Review
Ras/mitogen-activated protein kinase pathway dysregulation results in a group of disorders, collectively termed as RASopathies. Neurofibromatosis type 1, Noonan syndrome, Noonan syndrome with multiple lentigines, Noonan syndrome/loose anagen hair, Legius syndrome, Costello syndrome, cardio-facio-cutaneous syndrome and capillary malformation-arteriovenous malformation are the well-recognized RASopathies. These are characterized by multi-organ tumours and hamartomas. Some other features in common are facial dysmorphism, skeletal abnormalities, congenital heart disease, neurocognitive abnormalities and risk of various solid-organ and haematological malignancies. Some of the RASopathies are heterogeneous, caused by several gene mutations resulting in variations in phenotypes and severity ranging from mild to fatal. Significant phenotypic overlaps among different disorders, often makes it difficult to pinpoint a clinical diagnosis. Specific cutaneous manifestations are present in some of the RASopathies and are often the earliest clinical signs/symptoms. Hence, dermatologists contribute significantly as primary care physicians by identifying disorder-specific cutaneous lesions. However, diagnostic work-up and management of these disorders are often multidisciplinary. Confirmation of diagnosis is possible only by genetic mapping in each case. Genetic counseling of the patients and the affected families is an important component of the management. The aim of this review is description of cutaneous manifestations of RASopathies in the background of multi-system involvement to enable dermatologists a comprehensive and logical approach to work up and diagnose such patients in the absence of facility for specific molecular testing.
Topics: Costello Syndrome; Dermatologists; Ectodermal Dysplasia; Humans; Noonan Syndrome; ras Proteins
PubMed: 35138057
DOI: 10.25259/IJDVL_799_20 -
Current Topics in Developmental Biology 2020Drosophila melanogaster embryos develop initially as a syncytium of totipotent nuclei and subsequently, once cellularized, undergo morphogenetic movements associated... (Review)
Review
Drosophila melanogaster embryos develop initially as a syncytium of totipotent nuclei and subsequently, once cellularized, undergo morphogenetic movements associated with gastrulation to generate the three somatic germ layers of the embryo: mesoderm, ectoderm, and endoderm. In this chapter, we focus on the first phase of gastrulation in Drosophila involving patterning of early embryos when cells differentiate their gene expression programs. This patterning process requires coordination of multiple developmental processes including genome reprogramming at the maternal-to-zygotic transition, combinatorial action of transcription factors to support distinct gene expression, and dynamic feedback between this genetic patterning by transcription factors and changes in cell morphology. We discuss the gene regulatory programs acting during patterning to specify the three germ layers, which involve the regulation of spatiotemporal gene expression coupled to physical tissue morphogenesis.
Topics: Animals; Body Patterning; Drosophila Proteins; Drosophila melanogaster; Embryo, Nonmammalian; Gastrula; Gastrulation; Gene Expression Regulation, Developmental; Signal Transduction; Transcription Factors; Zygote
PubMed: 31959292
DOI: 10.1016/bs.ctdb.2019.11.004 -
Development (Cambridge, England) Apr 2022Developing organs are shaped, in part, by physical interaction with their environment in the embryo. In recent years, technical advances in live-cell imaging and... (Review)
Review
Developing organs are shaped, in part, by physical interaction with their environment in the embryo. In recent years, technical advances in live-cell imaging and material science have greatly expanded our understanding of the mechanical forces driving organ formation. Here, we provide a broad overview of the types of forces generated during embryonic development and then focus on a subset of organs underlying our senses: the eyes, inner ears, nose and skin. The epithelia in these organs emerge from a common origin: the ectoderm germ layer; yet, they arrive at unique and complex forms over developmental time. We discuss exciting recent animal studies that show a crucial role for mechanical forces in, for example, the thickening of sensory placodes, the coiling of the cochlea and the lengthening of hair. Finally, we discuss how microfabricated organoid systems can now provide unprecedented insights into the physical principles of human development.
Topics: Animals; Ear, Inner; Ectoderm; Embryo, Mammalian; Mechanical Phenomena; Sensation
PubMed: 35356969
DOI: 10.1242/dev.197947 -
Journal of Developmental Biology Jan 2023The integument of vertebrates is a complex and large organ positioned at the interface with the aquatic or terrestrial environment, and is derived from the embryonic...
The integument of vertebrates is a complex and large organ positioned at the interface with the aquatic or terrestrial environment, and is derived from the embryonic ectoderm (epidermis) and mesoderm (dermis and hypodermis) [...].
PubMed: 36810459
DOI: 10.3390/jdb11010007 -
Journal of Otology Sep 2019The utilization of biomarkers for and research is growing rapidly. This is mainly due to the enormous potential of biomarkers in evaluating molecular and cellular... (Review)
Review
The utilization of biomarkers for and research is growing rapidly. This is mainly due to the enormous potential of biomarkers in evaluating molecular and cellular abnormalities in cell models and in tissue, and evaluating drug responses and the effectiveness of therapeutic intervention strategies. An important way to analyze the development of the human body is to assess molecular markers in embryonic specialized cells, which include the ectoderm, mesoderm, and endoderm. Neuronal development is controlled through the gene networks in the neural crest and neural tube, both components of the ectoderm. The neural crest differentiates into several different tissues including, but not limited to, the peripheral nervous system, enteric nervous system, melanocyte, and the dental pulp. The neural tube eventually converts to the central nervous system. This review provides an overview of the differentiation of the ectoderm to a fully functioning nervous system, focusing on molecular biomarkers that emerge at each stage of the cellular specialization from multipotent stem cells to completely differentiated cells. Particularly, the otic placode is the origin of most of the inner ear cell types such as neurons, sensory hair cells, and supporting cells. During the development, different auditory cell types can be distinguished by the expression of the neurogenin differentiation factor1 (Neuro D1), Brn3a, and transcription factor GATA3. However, the mature auditory neurons express other markers including βIII tubulin, the vesicular glutamate transporter (VGLUT1), the tyrosine receptor kinase B and C (Trk B, C), BDNF, neurotrophin 3 (NT3), Calretinin, etc.
PubMed: 31467504
DOI: 10.1016/j.joto.2019.03.001